Lipid Structure Reza Meshkani, PhD Department of Biochemistry Faculty of Medicine Tehran University...
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Lipid Structure Reza Meshkani, PhD Department of Biochemistry Faculty of Medicine Tehran University of Medical Sciences
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Transcript of Lipid Structure Reza Meshkani, PhD Department of Biochemistry Faculty of Medicine Tehran University...
Lipid Structure
Reza Meshkani PhDDepartment of Biochemistry
Faculty of MedicineTehran University of Medical Sciences
Introduction
1 The role of Lipids2 Main components and Properties of Lipids3 Classification of lipids- Triglycerides- Phospholipids- Sterols- Ecosanoids- Isoprenoids4-Lipid Digestion5- Transport of lipids6- Lipoprotein Metabolism
پاسخ به قادر بايستي دانشجويان درس انتهاي درباشند زير سواالت به
ليپيدها bull دهنده تشكيل اجزاءليپيدها bull دهنده تشكيل اجزاء ويژگيهاي و خواصليپيدها bull بندي طبقهليپيدها bull از كدام هر اهميت و ساختمان
Lipids Functions
1 Provide Energy (9 kcalg)
2 Protects vital organs against shock
3 Insulates body against temperature extremes
4 Carrier of fat soluble vitamins ADE and K
5 Give flavor to foods
6 Important components of membranes
7 Helps body use carbohydrates and protein efficiently
Lipid Components
Fatty acids AlcoholEster band=R1COOR2Amid band=R1CONR2
SaturatedUnsaturated
GlycerolPhosphoglycerol
SterolsSphingosine
Lipid Components
bull long chain linear hydrocarbons carboxylic acids
bull Usually have an even number of C atoms (usually 12 to 20)
bull The carbons are numbered starting from the carboxylic C
bull They are amphiphilic they have a polar end and rest of the molecule is nonpolar
bull Fatty acids may be saturated (no double bonds) or unsaturated(one or more double bonds)
bull All naturally occurring double bonds have a cis-configuration
bull Longer chain and saturation increases melting point of FA
Fatty Acids
متعلقات
چون bull امینه اسیدهای هیدروکربنی های زنجیرهکو استیل استیل ( Aازاجتماع شود می ایجاد ها
) Aکو است کربنه دو تعداد اغلبترکیبی دارای باشد می کربن از زوجی
Function of Fatty Acids
bull 1 Fuel and energy metabolism ndash free fatty acids and triglyceride
bull 2 Membrane structure ndash complex lipids
bull 3 Cholesterol metabolism ndash cholesteryl ester is the major form in which cholesterol is transported or stored
bull 4 Metabolic regulators ndash free fatty acids eicosanoids complex lipids
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Introduction
1 The role of Lipids2 Main components and Properties of Lipids3 Classification of lipids- Triglycerides- Phospholipids- Sterols- Ecosanoids- Isoprenoids4-Lipid Digestion5- Transport of lipids6- Lipoprotein Metabolism
پاسخ به قادر بايستي دانشجويان درس انتهاي درباشند زير سواالت به
ليپيدها bull دهنده تشكيل اجزاءليپيدها bull دهنده تشكيل اجزاء ويژگيهاي و خواصليپيدها bull بندي طبقهليپيدها bull از كدام هر اهميت و ساختمان
Lipids Functions
1 Provide Energy (9 kcalg)
2 Protects vital organs against shock
3 Insulates body against temperature extremes
4 Carrier of fat soluble vitamins ADE and K
5 Give flavor to foods
6 Important components of membranes
7 Helps body use carbohydrates and protein efficiently
Lipid Components
Fatty acids AlcoholEster band=R1COOR2Amid band=R1CONR2
SaturatedUnsaturated
GlycerolPhosphoglycerol
SterolsSphingosine
Lipid Components
bull long chain linear hydrocarbons carboxylic acids
bull Usually have an even number of C atoms (usually 12 to 20)
bull The carbons are numbered starting from the carboxylic C
bull They are amphiphilic they have a polar end and rest of the molecule is nonpolar
bull Fatty acids may be saturated (no double bonds) or unsaturated(one or more double bonds)
bull All naturally occurring double bonds have a cis-configuration
bull Longer chain and saturation increases melting point of FA
Fatty Acids
متعلقات
چون bull امینه اسیدهای هیدروکربنی های زنجیرهکو استیل استیل ( Aازاجتماع شود می ایجاد ها
) Aکو است کربنه دو تعداد اغلبترکیبی دارای باشد می کربن از زوجی
Function of Fatty Acids
bull 1 Fuel and energy metabolism ndash free fatty acids and triglyceride
bull 2 Membrane structure ndash complex lipids
bull 3 Cholesterol metabolism ndash cholesteryl ester is the major form in which cholesterol is transported or stored
bull 4 Metabolic regulators ndash free fatty acids eicosanoids complex lipids
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
پاسخ به قادر بايستي دانشجويان درس انتهاي درباشند زير سواالت به
ليپيدها bull دهنده تشكيل اجزاءليپيدها bull دهنده تشكيل اجزاء ويژگيهاي و خواصليپيدها bull بندي طبقهليپيدها bull از كدام هر اهميت و ساختمان
Lipids Functions
1 Provide Energy (9 kcalg)
2 Protects vital organs against shock
3 Insulates body against temperature extremes
4 Carrier of fat soluble vitamins ADE and K
5 Give flavor to foods
6 Important components of membranes
7 Helps body use carbohydrates and protein efficiently
Lipid Components
Fatty acids AlcoholEster band=R1COOR2Amid band=R1CONR2
SaturatedUnsaturated
GlycerolPhosphoglycerol
SterolsSphingosine
Lipid Components
bull long chain linear hydrocarbons carboxylic acids
bull Usually have an even number of C atoms (usually 12 to 20)
bull The carbons are numbered starting from the carboxylic C
bull They are amphiphilic they have a polar end and rest of the molecule is nonpolar
bull Fatty acids may be saturated (no double bonds) or unsaturated(one or more double bonds)
bull All naturally occurring double bonds have a cis-configuration
bull Longer chain and saturation increases melting point of FA
Fatty Acids
متعلقات
چون bull امینه اسیدهای هیدروکربنی های زنجیرهکو استیل استیل ( Aازاجتماع شود می ایجاد ها
) Aکو است کربنه دو تعداد اغلبترکیبی دارای باشد می کربن از زوجی
Function of Fatty Acids
bull 1 Fuel and energy metabolism ndash free fatty acids and triglyceride
bull 2 Membrane structure ndash complex lipids
bull 3 Cholesterol metabolism ndash cholesteryl ester is the major form in which cholesterol is transported or stored
bull 4 Metabolic regulators ndash free fatty acids eicosanoids complex lipids
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Lipids Functions
1 Provide Energy (9 kcalg)
2 Protects vital organs against shock
3 Insulates body against temperature extremes
4 Carrier of fat soluble vitamins ADE and K
5 Give flavor to foods
6 Important components of membranes
7 Helps body use carbohydrates and protein efficiently
Lipid Components
Fatty acids AlcoholEster band=R1COOR2Amid band=R1CONR2
SaturatedUnsaturated
GlycerolPhosphoglycerol
SterolsSphingosine
Lipid Components
bull long chain linear hydrocarbons carboxylic acids
bull Usually have an even number of C atoms (usually 12 to 20)
bull The carbons are numbered starting from the carboxylic C
bull They are amphiphilic they have a polar end and rest of the molecule is nonpolar
bull Fatty acids may be saturated (no double bonds) or unsaturated(one or more double bonds)
bull All naturally occurring double bonds have a cis-configuration
bull Longer chain and saturation increases melting point of FA
Fatty Acids
متعلقات
چون bull امینه اسیدهای هیدروکربنی های زنجیرهکو استیل استیل ( Aازاجتماع شود می ایجاد ها
) Aکو است کربنه دو تعداد اغلبترکیبی دارای باشد می کربن از زوجی
Function of Fatty Acids
bull 1 Fuel and energy metabolism ndash free fatty acids and triglyceride
bull 2 Membrane structure ndash complex lipids
bull 3 Cholesterol metabolism ndash cholesteryl ester is the major form in which cholesterol is transported or stored
bull 4 Metabolic regulators ndash free fatty acids eicosanoids complex lipids
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Lipid Components
Fatty acids AlcoholEster band=R1COOR2Amid band=R1CONR2
SaturatedUnsaturated
GlycerolPhosphoglycerol
SterolsSphingosine
Lipid Components
bull long chain linear hydrocarbons carboxylic acids
bull Usually have an even number of C atoms (usually 12 to 20)
bull The carbons are numbered starting from the carboxylic C
bull They are amphiphilic they have a polar end and rest of the molecule is nonpolar
bull Fatty acids may be saturated (no double bonds) or unsaturated(one or more double bonds)
bull All naturally occurring double bonds have a cis-configuration
bull Longer chain and saturation increases melting point of FA
Fatty Acids
متعلقات
چون bull امینه اسیدهای هیدروکربنی های زنجیرهکو استیل استیل ( Aازاجتماع شود می ایجاد ها
) Aکو است کربنه دو تعداد اغلبترکیبی دارای باشد می کربن از زوجی
Function of Fatty Acids
bull 1 Fuel and energy metabolism ndash free fatty acids and triglyceride
bull 2 Membrane structure ndash complex lipids
bull 3 Cholesterol metabolism ndash cholesteryl ester is the major form in which cholesterol is transported or stored
bull 4 Metabolic regulators ndash free fatty acids eicosanoids complex lipids
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
bull long chain linear hydrocarbons carboxylic acids
bull Usually have an even number of C atoms (usually 12 to 20)
bull The carbons are numbered starting from the carboxylic C
bull They are amphiphilic they have a polar end and rest of the molecule is nonpolar
bull Fatty acids may be saturated (no double bonds) or unsaturated(one or more double bonds)
bull All naturally occurring double bonds have a cis-configuration
bull Longer chain and saturation increases melting point of FA
Fatty Acids
متعلقات
چون bull امینه اسیدهای هیدروکربنی های زنجیرهکو استیل استیل ( Aازاجتماع شود می ایجاد ها
) Aکو است کربنه دو تعداد اغلبترکیبی دارای باشد می کربن از زوجی
Function of Fatty Acids
bull 1 Fuel and energy metabolism ndash free fatty acids and triglyceride
bull 2 Membrane structure ndash complex lipids
bull 3 Cholesterol metabolism ndash cholesteryl ester is the major form in which cholesterol is transported or stored
bull 4 Metabolic regulators ndash free fatty acids eicosanoids complex lipids
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
چون bull امینه اسیدهای هیدروکربنی های زنجیرهکو استیل استیل ( Aازاجتماع شود می ایجاد ها
) Aکو است کربنه دو تعداد اغلبترکیبی دارای باشد می کربن از زوجی
Function of Fatty Acids
bull 1 Fuel and energy metabolism ndash free fatty acids and triglyceride
bull 2 Membrane structure ndash complex lipids
bull 3 Cholesterol metabolism ndash cholesteryl ester is the major form in which cholesterol is transported or stored
bull 4 Metabolic regulators ndash free fatty acids eicosanoids complex lipids
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Function of Fatty Acids
bull 1 Fuel and energy metabolism ndash free fatty acids and triglyceride
bull 2 Membrane structure ndash complex lipids
bull 3 Cholesterol metabolism ndash cholesteryl ester is the major form in which cholesterol is transported or stored
bull 4 Metabolic regulators ndash free fatty acids eicosanoids complex lipids
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
1 Short Chain fatty acidsLess than 6 carbons (most in dairy products)
Length of Fatty Acids
2 Medium Chain fatty acids6-10 carbons
3 Long Chain fatty acids12-22 carbons (most common in the diet)
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Nomenclature 1- Based on hydrocarbon molecule with the number and arrangement of carbon atoms
saturated = anoic octanoic acid (octa =8)
unsaturated = enoic octadecenoic acid (octa = 8 and deca = 10 thus 18)
bullPalmitic (hexadecanoic)160bullPalmitoleic acid 9-hexadecenoic acidbullStearic acid Octadecanoic acid) 180bullOleic Acid (Δ9-octadecenoic)181 Δ 9bullArachdonic acid (Δ 581114-eicosatetraenoic acid)
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Nomenclature 2- Terminal methyl carbon (CH3) as n-carbon or ω-carbon
bullThe carbon atom adjacent to the carboxyl carbon (No2) is known as the α carbon
bull ω9 = indicates first or only double bond on the ninth carbon counting from the terminal methyl (omega) carbon (n)
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
امگا bull ی شیوه به چرب اسیدهای نامگذاری برایداشته زنجیره در دوگانه باند که هم هرچندتا ما
را فقطباشیم دوگانه باند اخرین که کربنی به ) از دوگانه باند اولین حقیقت در داریم کار داده
اخر)
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Nomenclature
3- unsaturated where isare double bond(s)
bull Δ9 = double bond between carbon atoms 9 and 10
bull Δ912 = double bonds between 9 and 10 12 and 13
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Nomenclaturebull 4-Classical name
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Fatty Acids1048708Saturated Fatty acids No double bonds1 lauric acid (laurate) (120)2 myristic acid (myristate) (140)3 palmitic acid (palmitate) (160)4 stearic acid (stearate) (180)
Monounsaturated Fatty Acids1048708 One double bond1 Oleic acid (oleate) (181cis)2 Elaidic acid (elaidate) (181trans)
Polyunsaturated Fatty Acids1048708 Two or more double bonds1 Linoleic acid (linoleate) (182 912) ω62 Linolenic acid (linolenate) (183 91215) ω33 Arachidonic acid (arachidonate) (204 581114) ω6
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
ω 3 and ω6 Fatty acidsOmega-3
bull ω-3 fatty acids (Linolenic) are found mainly in fish and fish products
bull ω-3 FAs inhibit formation of thromboxane A2 (an eicosanoid) required for platelet aggregation and clot formation Thus ω-3 FAs decrease the risk of heart disease
Omega-6Linoleic acid Vegetable oils (corn safflower soybean cottonseed sesame sunflower)
Arachidonic acid Meats (can be made from linoleic acid)
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
با bull چربی اسید توانند نمی یوکاریوتی های سلول ) رو این از بسازند دوگانه باند یک از چرب بیش اسید
تعداد ضروری یا دو که میشود اطالق چربی اسید بهاسید نوع این که باشد داشته دوگانه باند بیشتری
( برسد بدن به غذایی رژیم طریق از باید چربغیرضروری bull می اسیدچرب گفته هایی اسیدچرب به
این باشد می انها سنتز به قادر خود بدن که شودیکی فقط یا ندارند دوگانه باند یا چرب اسیدهای
دارند
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Palmitic acid
bull The most common saturated fatty acid found in animals and plants
bull Palmitic acid is the first fatty acid produced during Lipogenesis (fatty acid synthesis)
bull Intake of palmitic acid increases risk of developing cardiovascular diseases
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Arachidonic acid
bull is present in the phospholipidsbull involved in cellular signaling as a lipid second
messenger
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Why are these essential
In most mammals double bonds can be formed at the Δ4 Δ5 Δ6 and Δ9 positions but never beyond Δ9 therefore any fatty acid that needs to add a double bond after Δ10 for example are essential
Essential FFA functions
Needed for eicosanoid production
Part of structural lipids of the cell and add structural integrity of mitochondrial membrane
Necessary for fetal development brain and retina (vision)
all saturated fatty acids are nonessential
all monounsaturated fatty acids are nonessential
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Alkali hydrolysis of fatty acids
R-COOH + NaOH KOH RCOONa+H2O
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Isomeration
saturated fatty acids (zig zag pattern)
unsaturated fatty acids1cis acyl chains are on the same side of the double bond (nearly all naturally occurring fatty acids)2 trans acyl chains are on opposite sides of the bond1048708 present in certain foods1048708 Most arise due to partial hydrogenation (saturation) of polyunsaturated fattyacids of natural oils (margarine)
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Hydrogenation
bullHydrogenation process of replacing some double bonds of polyunsaturated fats with hydrogen atoms The process by which vegetable oil becomes margarine
bull When vegetable oils are hydrogenated some double bonds undergo a change in configuration and are concerted to ldquoTrans Fatty Acidsrdquo
bullThe ldquoCisrdquo configuration is typical of the fatty acid in natural foods
bullThe ldquoTransrdquo fatty acids (formed during hydrogenation) may raise LDL and lower HDL level
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
1048708 melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation
1048708 saturated long-chain fatty acids are solid at body temperature (high melting point)
1048708 polyunsaturated fatty acids are liquid at 0degC (low melting point) The membrane lipids which must be fluid at all environmental temperatures are more unsaturated
Question
Melting Temperature
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and also damage of tissues which causes cancer inflammatory disease atherosclerosis etc
The reaction is initiated by an existing free radical (X ) by light or by metal
The deterioration effects cause by free radicals (ROO RO
OH
) produced during
peroxide formation from fatty acids (unsaturated)
Lipid peroxidation
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
غیراشباع bull چرب اسیدهای اکسیداسیون طیازاد های راذیکال موجود های رادیکال توسط
دوباره اینها که ایند می وجود به دیگریکنندگی خودشان تشدید اثر دارند چرخه این بر
در bull بیشتر ازاد های وجود میتوکندریرادیکال به ایند می
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Lipid peroxidationAnti-oxidants - BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) are antioxidants used as food derivates-Vit E C Beta carotene glutathion( است سلولی داخل عامل (گلوتاتیون-Catalase superoxid dismutase lipooxygenase
Polyunsaturated fats spoil more easily than saturated fatsRancidity Flavor and odor of fat is affected due to the oxidation of double bonds
To protect polyunsaturated fats from rancidity1 Refrigeration3 Hydrogenation
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Alcohol
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
bull Sterols Lipids containing multiple rings of carbon atomsndash Are essential components of cell membranes and many hormonesndash Are manufactured in our bodies and therefore are not essential components of our diet
Sterols are basis of Cholesterol Bile Acids Steroid hormones and Vitamin D
Sterol
فنانترن پرهيدروپنتانو سيكلو
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Sphingosine
CH3-(CH2)12-CH=CH-CH-CH-CH2OH
OH
NH2
Fatty acid
Sphingosine is basis of Sphingolipids
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Classification of Lipids
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Triglyceridesbull In Triacylglycerol (TG) all 3 ndashOH of glycerol are esterified by FAs
Monoacylglygerol and diacylglycerol have respectively 1 and 2 FAsbull Naturally occurring glycerol is L-glycerol
bull TG are the storage form of FA most dietary fats are triglycerides
bull Physiologically TG are digested in the small intestine by the enzyme pancreatic lipasebull Monoacylglycerols are absorbed through the intestinal cells re-converted to TG and assembled into lipoproteins
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
گلیسیرید bull تریغذایی 1bull رژیم از دربافتی لیپید بیشترینذخیره 2bull گلیسیرید تری صورت به دربدن ها چربی
شوند میهستند 3bull زیادی تنوع دارایاشباع 4bull غیر گلیسیرید تری زنجیره دومین معموال
استاز bull کمتر پالسما یافت 150در لیتر دسی گرم میلی
شود می
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Triglyceridesbull Fatty acids can differ in
ndash Length of their carbon chainbull Short- medium- or long-chain
ndash Level of saturationbull Saturation refers to how many hydrogen atoms surround each carbon
ndash ShapeThe shape of a triglyceride is determined by the saturation of the carbon chainsbull Saturated fatty acids can pack tightly together and are solid at room temperaturendash For example animal fats butter and lard are high in saturated fatty acids
Unsaturated fatty acids do not stack together well and are liquid at room temperaturendash Plant oils have unsaturated fatty acids
Normal Plasma TG levels lt150mgdl
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Phospholipids
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
General Structure of Glycerophospholipid
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure of glycerophospholipids
Phosphatidate
Net ChargepH 7 = -1
X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
High amount of circulation PL (69)
A PL that is used in plasma membrane
The most common PL in the membrane
PLC is a store of Choline in the body
Dipalmitoyl Lecithin is a surfactant
Phosphatidyl Choline (Lecithin)
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
PhosphatidylcholineFunctionsbull Choline is required for the proper metabolism of fats
-Facilitates the movement of fats in and out of cells In liver it exports the fat from the hepatocytes (Choline deficiency=Fat accumulation fatty liver cirrhosis)
bull Like Vitamin B12 5-adenosylmethionine and Folic Acid choline acts in the human body as a methyl donor
bull Choline is needed for cell membrane integrity because of the critical role it plays in the manufacture of primary components of cell membranes such as phosphatidylcholine and sphingomyelin
bull Choline is essential in the synthesis of acetylcholine Choline supplementation increases the accumulation of acetylcholine which plays a crucial role in many brain processes including memory
bull Phosphatidylcholine increases the solubility of cholesterol and thereby decreases cholesterollsquos ability to induce atherosclerosis
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Therapeutic Uses
bull Liver Disordersbull Detoxificationbull Hypercholesterolemia and Atherosclerosisbull Manic depressive disorderbull Alzheimerrsquos Disease
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقاتbull( لسیتین ( کولین فسفاتیدیلدارو1bullخارجی 2bull بخش در غشا فسفولیپید مقدار بیشترbull3( ) کبد مخصوصا درغشا سلولی تبادالت به کمکbull4) ب متیل گروه دهنده ndash 12دهنده دیگر از ومتیونین اسیدفولیک
( هستند متیل گروه هایغشا 5bull تعادلمانع bull نتیجه در شود حل پالسما در کلسترول تا میشود باعث
میشود کلسترول رسوببیماری bull درمان در موثر کولین سنتزاستیل افزایش
مثل هاییbull- - دپرشن- سیروز و هپاتیت مانند کبدی های بیماری مسمومیت
-( دارند( باال کلسترول که افرادی حافظه تقویت به کمک الزایمر
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Phospholipase A2
Arachidonic Acid
Lysolecithin
At high concentration acts a Emulicification of triglycerides
ProstaglandinesLeukoterinesTromboxaneProstacycline
Phosphatidyl Choline=Lecithin
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
LCAT (Lecitin Cholesterol Acyl Transferase)
Cholesterol ester
Lysolecithin7 of Plasma membrane PL
Phosphatidyl Choline=Lecithin
Fatty Acid
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Ether Lipids(Plasmalogen [phosphatidal]amp
Platelete activating factor [PAF])
Similar to Lecithin except that instead of ester link they have ether linkPlasmalogen has unsaturated Acyl group and PAF has saturated
Plasmalogen (Phosphatidal)The heart of vertebrates is rich of ether lipidsThe importance is unknown it seems that these ether link protected phospholipids from phospholipase activity
PAFReleased from Basophiles and stimulated platelet to secrete Serotonin
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Phospholipase C
Inositol 3 phosphate=IP3
Diacelglycerol=DAG
DAGActivation of protein kinase C and phosphorylation of target proteins
IP3Release of Ca from endotelium And regulating activation of proteins
Phosphatidyl 45 bisphosphate
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = 0
5 of circulation PLIsolated from Brain
Phosphatidyl Ethanolamine (Cephalin)
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
bull Phosphatidylethanolamine is the second most abundant phospholipid in animal and plant lipids and is the main lipid component of microbial membranes
bull It can amount to 20 of liver phospholipids and as much as 45 of those of brain
bull In contrast to phosphatidylcholine it is concentrated with phosphatidylserine in the inner leaflet of the plasma membrane
Functions-secretion of the nascent very-low-density lipoproteins from liver-membrane fusion and fission یعنی فیوژن ها میتوکندری افزایش یعنی فیژن
( سلول دو (ادغام-Integration of plasma membrane
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Phosphatidyl Glycerol
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
Net ChargepH 7 = -1
Is seen in mitochondria and chloroplast
Phosphatidyl Glycerol + Phosphatidic Acid
Cardiolipin
Inner mitochondrial membrane where it constitutes about 20 of the total lipid composition
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Cardiolipinbull Cardiolipin (bisphosphatidyl glycerol) is an important component of the inner
mitochondrial membrane where it constitutes about 20 of the total lipid
FunctionsoRegulates aggregate structureso Helps to build quaternary structureo Triggers apoptosiso Serves as proton trap for oxidative phosphorylationo Cholesterol translocation from outer to the inner membrane of mitochondrial o Import protein into mitochondrial
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
میتدکندری bull الکترون انتقال زنجیره در مهم کمپلکسbullNADH- دهیدروژناز- تولسینات دهیدروژناز
اکسیداز- bc1کمپلکس cسیتوکرومbull کاردیولیپین کمپلکسها 1نقشهای کردن نزدیک
سیتوکروم 2 انزیم چهارم ساختمان پایدارکردنc اکسیداز
میتوکندری 3bull در پروتون انداختن دام به عامل4 ) راه اپوپتوز سلول شده ریزی برنامه مرگ
( سرطان ازخارج 5درمانی را وکلسترول پروتییناورد می میتوکندری داخل به
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Clinical significance
- Barth syndrome- disease state (an infantile cardiomyopathy) linked to the X-chromosome
is associated with marked abnormalities in the composition of cardiolipin- It has a mutation in the gene coding for Tafazzin (an acyltransferase) an
enzyme involved in the biosynthesis of cardiolipin Girls heterozygous for the trait are unaffected
-Diabetes-Cancer (A study published in 2009 suggests that cardiolipin abnormalities can
underlie the irreversible respiratory injury in tumors Cardiolipin is an essential part of one pathway which triggers apoptosis (cell death)
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
اپوپتوز bull مراحلمیچرخد bull غشا بیرون به کاردیولیپین
اکسیداز شبکه cسیتوکروم سیتوزولمیشود ازاد کلسیم اندوپالسمی
سلول مرگ
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
PhospholipasesPLA1
PLA2
PLC
PLD
PI45BP
DAG
IP3
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Indican Cobra Eastern Diamondback Rettlesnake
oThe Poisonous Snakes contain phospholipase A2 that breakdown Lecithin and produces Lysolecithin
oLysolecithin acts a detergent and dissolves of membrane of red blood cells
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Sphingolipids
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Sphingosine Sphingosine +H= Ceramide
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
سلول bull چرب اسید بیشترین عنوان به پالمیتاتاست ای ذخیره و زایی انرژی نقش دو دارای
ایجاد مضری های متابولیت شود ذخیره زیاد اگر ( که( گلیسرول اسیل دی و سرامید مثل کرده
و شده سلول به گلوکز ورود مانع سرامیدسلولی مسیرهای شدن فعال باعث همینطور
میشود
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
SphingophospholipidSphingomyelin
Phosphocholine
The most common sphingolipidIs found in Central nervous system and Myelin membrane
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
SphingoglycolipidCerebrosides
Sphingosine + Glucose= Glucocerebroside (found in RBC WBC Membrane)
Sphingosine + Galactose= Galactocerebroside (found in Brain)
Galactocerebroside+ Sulfate= Sulfatide
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
GangliosidesComplex Cerebroside
GM1
O antigen A antigen B antigen
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Gangliosidebull Ganglioside is a compound composed of a glycosphyngolipid with one or
more sialic acid (n-acetylneuraminic acid NANA)bull The 60+ known gangliosides differ mainly in the position and number of
NANA residues
Locationbull on cell surfaces with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the extracellular surface
bull They are found predominantly in the nervous system where they constitute 6 of all phospholipids
bull Function ( پیوند (ردbull Gangliosides glycosphingolipids and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition (signal transduction) and cell-to-cell communication
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Ganglioside nomenclature
bull common gangliosides GM1 GM2 GM3 GD1a GD1b GT1a GT1b Gq1b
bull letter G refers to the name ganglioside
bull the subscripts M D T and Q indicate mono- di- tri and quatra(tetra)-sialic-containing gangliosides
bull the numerical subscripts 1 2 and 3 designate the carbohydrate sequence attached to ceramide
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Ganglioside nomenclaturebull Numerical subscripts
bull 1 Gal-GalNAc-Gal-Glc-ceramidebull 2 GalNAc-Gal-Glc-ceramidebull 3 Gal-Glc-ceramide
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
O
CH2OH
H OH
H
OH
OH
O
O
CH2OH
H NH
H
OH
O
CH2OH
H OH
H
H
O
CH2OH
H OH
H
H
OH H
O
H
O
O
CH2HC
HC
NH
C O
R
HO
C
C
O
O
C O
CH3
NH
H
CHOH
CHOH
OH
CH2OH
H
H
COO-C
O
H3C
H
H
H
H
D-Galactose
N-Acetyl-D-galactosamine D-galactose D-glucose
N-acetylneuraminidate (sialic acid)
A ganglioside (GM1)
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Gangliosidoses (Lipid Storage Diseases)
bull Mutations in genes coding for enzymes of ganglioside metabolism
bull Tay-sachs disease (deficiency of beta galactosidase)
bull Sandhoff disease (Deficiency in hexoseaminidase)
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Waxes
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
SteroidsSterolsCholesterol StigmasterolSitosterol
Steroid Hormonesprogesterone cortisol Aldosterone testosteroneEstradiolcalcitriol
Bile acidsprimary bile acidsCholic acidChenodeoxycholic acid
secondary bile acidslithocholic aciddeoxycholic acid
Vitamin D
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Cholesterol
o Component of cell membranesoCan be made by the bodyo Not an essential nutriento Forms the major parts of the plaques that narrow arteries in atherosclerosiso The underlying cause of heart attacks and strokeso Exclusively synthesized by animalso Not readily catabolized for energyo Present in all tissueo Converted in liver to bile acidso Converted by gonads and adrenals into steroid hormones
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
مانند bull گیاهی منشا کلسترول شبهsitosterol-stigmastrol
انرا bull ومیتوانند نیازداشته کلسترول به سلولها تمامغذایی رژیم از را ان میدهند ترجیح ولی بسازند
بگیرنداستفاده bull انرژی تامین عنوان به بدن در کلسترول
نمیشودbull( ) میشود حیوانی سلول غشای غشا سیالیت باعث
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
OR
O
usually palmitate
drawn this way
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Bile Acids
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Steroids Hormones
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
ProgesteroneIt is synthesized in the corpus luteum of the ovaries
The hormone prepares the uterus for a possible pregnancy
The development of the mammary glands is also stimulated by progesterone
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
EstradiolEstradiol is the most important of the estrogens
Like progesterone it is synthesized by the ovaries and during pregnancy by the placenta as well
Estradiol controls the menstrual cycle
It promotes proliferation of the Uterine mucosa and is also responsible for thedevelopment of the female secondary sexual characteristics (breast fat distribution)
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
CortisoleCortisol the most important glucocorticoid is synthesized by the adrenal cortex
It is involved in regulating protein and carbohydrate metabolism by promoting protein degradation and the conversion of amino acids into glucose
As a result the blood glucose level rises
Synthetic glucocorticoids (e g dexamethasone) are used in drugs due to their anti-inflammatory and immunosuppressant effects
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
TestosteroneTestosterone is the most important of the male sexual steroids (androgens)
It is synthesized in the Leydig intersitial cells of the testes and controls the development and functioning of the male gonads
It also determines secondary sexual characteristics in men (muscles hair etc)
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
AldosteroneAldosterone a mineralocorticoid is also synthesized in the adrenal gland In the kidneys
it promotes Na+ resorption by inducing Na+K+ ATPase and Na+ channels
At the same time it leads to increased K+ excretion In this way aldosterone indirectly increases blood pressure
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
CalcitriolCalcitriol is a derivative of vitamin D
Calcitriol itself is synthesized in the kidneys
Calcitriol promotes the resorption of calcium in the intetine and increases the Ca2+ level in the blood
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Vitamin D
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
bull Eicosanoid horomones are synthesized from arachadonic acid (204)ndash Prostaglandinsndash Prostacyclinsndash Thromboxanesndash Leukotrienes
Eicosanoid Hormones
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Eicosanoid Hormonesbull Eicosanoids are oxygenated derivates of polyunsaturated 20-carbon fatty acidsbull Most cells except red blood cells produce eicosanoidsbull Have profound physiological effects at extremely low concentrations
bull They have specific effects on target cells close to their site of formation
bull They are rapidly degraded so they are not transported to distal sites within the body
bull Effects
-Inflammatory response to damaged tissue- Production of pain and fever- Regulation of blood pressure-Induction of blood clotting- Control of reproduction functions- Regulation of sleepwake cycle
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Eicosanoid
Prostaglandins all have a cyclopentane ring A letter code is based on ring modifications (eg hydroxyl or
keto groups) A subscript refers to the number of double bonds in the two
side-chains
Prostacyclin= Prostaglandin I2 (PGI2)
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
O
R1
R2
O
R1
R2
PGA PGB
O
R1
R2
PGC
R1
R2
HO
OPGD
R1
R2
O
HO
R1
R2
HO
HO
R1
R2
O
O
PGE PGFa PGG and PGHR2
HO
O
R1
R1
R2
O
PGJ
R1
R2
O
O
PGK
PGI
O
O
R1
R2 O
R1
R2HO
OH
TXA TXB
SUBSTITUTION PATTERN OF PROSTANOIDS
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
EICOSANOIDS
Physiological functions of eicosanoids
EicosanoidFunctions
prostaglandinsشاخمهم صه
ضلعی 5حلقهعفونت درمان به کمک
inflammation fever production prevent platelet aggregation (prevent clotting) induce labor
thromboxanesproduced by platelets to promote their aggregation (blood clotting)
leukotrienesallergic reactions درفرایندالتهابمیشود ازاد ازلوکوسیت
Eicosanoids act via membrane receptors in the immediate vicinity of their site of synthesis both on the synthesizing cell itself (autocrine action) and on neighboring cells (paracrine action)
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
93
Eicosanoid Hormones
inhibited by aspirin ibuprofen
inhibited by glucocorticoids
Or Cyclooxygenase (COX)
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
متعلقات
دارد bull حفاظتی نقش معده در پروستوگالندیناسیدمعده bull تا میشود باعث پروستوگالندین
موکوز+
bullIbuprofen کاهش سبب شود مصرف زیاد اگرباال فلشهای شدن برعکس وبا شده پروستوگالندین
معده میکند زخم ایجاد
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Prostaglandin H2 Synthase catalyzes the committed step in the ldquocyclic pathwayrdquo
PGH2 Synthase is a heme-containing dioxygenase bound to ER membranes
(A dioxygenase incorporates O2 into a substrate)
PGH2 Synthase exhibits 2 activities cyclooxygenase amp peroxidase
PGH2 Synthase (expressing both cyclooxygenase amp peroxidase activities) is sometimes referred to as Cyclooxygenase abbreviated COX
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibit cyclooxygenase activity of PGH2 Synthase
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Effects of Prostaglandins
bull Stimulate or inhibit smooth-muscle contractionStimulate or inhibit smooth-muscle contraction
bull Inhibit HCl secretion in the stomach particularly PGEInhibit HCl secretion in the stomach particularly PGE11
bull Promote mucus secretion which protects the gastric mucosa against the acidPromote mucus secretion which protects the gastric mucosa against the acid
bull In the immune system prostaglandins attract leukocytes to the site of infectionIn the immune system prostaglandins attract leukocytes to the site of infection
bull PGFPGF22 ndash causes constriction of the uterus ndash causes constriction of the uterus
bull PGEPGE22 is applied locally to help induce labor at term is applied locally to help induce labor at term
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
NSAIDs (Non steroid anti-inflammatory drugs)
Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase and consequently the synthesis of most eicosanoids
Aspirin acetylates a serine hydroxyl group near the active site preventing arachidonate binding The inhibition by aspirin is irreversible
Most other NSAIDs such as indomethacin and ibuprofen inhibit cyclooxygenases by competing with arachidonate
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
bull Side effects of NSAIDsbull Impairing hemostasis because of inhibiting synthesis of
thromboxanes by thrombocytes
bull Increasing HCl secretion and inhibiting the formation of protective mucus
bull Long-term NSAID use damages the gastric mucosa
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Selective COX inhibitors
bull Celecoxibbull Rofecoxibbull Because COX-2 is usually specific to inflamed tissue there is much less
gastric irritation associated with COX-2 inhibitors with a decreased risk of peptic ulceration
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Lipid transport in the circulationLipids are insoluble in plasma In order to be transported they are combined with specific proteins to form lipoproteins
Non polar lipids in core (TAG and cholesterol ester)
Proteins (apoproteins)
Cholesterol
Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class Apoproteins have various functions including bull Structural role bull Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism
HO
HO
O
R
HOHO
O
R
HOHO
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Physiological Function
bull Transport lipid from exogenous (diet) or endogenous (de novo synthesis) sources for delivery to cells and tissues for energy storage or building block components
bull Transport fat-soluble vitamins
bull Transport fat-soluble drugs
bull Delivery of cholesterol to steroid hormone producing tissues
bull They have a critical role in atherosclerosis
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Functions of Apoproteins (Apo)
bull Structuralndash Serve to stabilize and maintain the molecular structure of the molecule
bull Regulatoryndash Cofactors for enzymes involved in lipoprotein metabolism
bull Mediationndash Serve as ligands for lipoprotein interactions with receptors
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Apoproteins of human lipoproteins
bull A-I (28300)- principal protein in HDLbull 90 ndash120 mg in plasma activates LCAT
bull A-II (8700) ndash occurs as dimer mainly in HDL30 ndash 50 mg enhances hepatic lipase activity
bull B-48 (240000) ndash found only in chylomicron lt5 mg derived from apo-B-100 gene by RNA editing lacks the LDL
receptor-binding domain of apo-B-100
bull B-100 (500000) ndash principal protein in LDL80ndash 100 mg binds to LDL receptor
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
bull C-I (7000) ndash found in chylomicron VLDL HDLbull 4 ndash 7 mg may also activate LCAT
bull C-II (8800) - found in chylomicron VLDL HDLbull 3 ndash 8 mg activates lipoprotein lipase
bull C-III (8800) - found in chylomicron VLDL IDL HDLbull 8 15 mg inhibits lipoprotein lipase
Apoproteins of human lipoproteins
bull D (32500) - found in HDL8 ndash 10 mg also called cholesterol ester transfer protein
(CETP)
bull E (34100) - found in chylomicron VLDL IDL HDL3 ndash 6 mg binds to LDL receptor
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Classification of Lipoproteins
bull Based on Electrophoresisbull Paper chylo beta prebeta alphabull PAGE chylo prebeta beta alpha
bull Density in centrifugationbull chylomicronsbull very low density lipoproteins (VLDL)bull intermediate density lipoproteins (IDL)bull low density lipoproteins (LDL)bull high density lipoproteins (HDL)
Chylomicron remains at origin in electrophoretic field
VLDL IDL Lpa in Prebeta
LDL BetaHDL Alpha
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
The five classes of lipoprotein(all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids
and apoproteins)
ClassDiameter
(nm)Source and functionMajor apoliproteins
Chylomicrons(CM)
500Intestine Transport of dietary TAGA B48 C(IIIIII) E
Very low density lipoproteins
(VLDL)
43Liver Transport of endogenously synthesised TAG
B100 C(IIIIII) E
Low density lipoproteins(LDL)
22Formed in circulation by partial breakdown of IDL Delivers cholesterol to peripheral
tissues
B100
High density lipoproteins(HDL)
8Liver Removes ldquousedrdquo cholesterol from tissues and
takes it to liver Donates apolipoproteins to CM and
VLDL
A C(IIIIII) D E
Incr
easi
ng d
ensi
ty
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Lipoprotein class
Density (gmL)
Diameter (nm)
Protein of dry wt
Phospholipid
Triacylglycerol of dry wt
HDL1063-1215 ndash 1533298
LDL1019 ndash 106318 ndash 2825214
IDL1006-101925 - 50182231
VLDL095 ndash 100630 - 80101850
chylomicronslt 095100 - 5001 ndash 2784
Composition and properties of human lipoproteins
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Isoprenoids
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Cholesterolbull Cholesterol is an essential component of biomembranesand imparts stability to the fluid structurebull Cholesterol is a steroid All steroids have the same basicstructure consisting of 4 hydrocarbon rings linkedtogetherbull Cholesterol has a ndashOH group which provides the polarityand a hydrocarbon group at the other end which adds toits hydrophobic naturebull In biomembranes the ndashOH of cholesterol is aligned withthe head group (phosphate) of phospholipidsbull Steroids are important metabolically (cholesterol) fordigestion (bile salts) as hormones (human sex hormones)
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Sphingolipids
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
Glc-Gal
OHO
CH=CH(CH 2)12CH3
CH
HC
H2C
N H
O
C(CH2)22CH3
OHO
CH=CH(CH 2)12CH3
Glc Gal Neu5Ac
GalNAc
S
General Structure Cer Sm
PC
GlcCb)neutral GL(
LacCer)Gb(
Gan)ie blood groups(
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Phospholipidsbull These are lipids that contain one or more phosphate groupsbull PL are the primary components of biomembranes Other lipidsin biomembranes are glycolipids and cholesterol Surfactantsare phopsholipids mostly phosphatidylcholinebull PL are subclassified based on their parent lipidphopshoglycerides or sphingomyelinsbull Phosphatidic acid basic glycerophopholipid 12-diacylglycerol joined to phosphoric acid by an ester link Thisphosphate can form another ester linkage with an alcoholSerine phosphatidylserine Choline phosphatidylcholineEthanolamine phosphatidylethanolamine Inositolphosphatidylinositol Glycerol diphosphatidylglycerol(cardiolipin)
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Diglyceride esterified with phosphoric acidwhich is bound as ester to nitrogencontainingbase or serine Named based on nature of ldquoheadrdquo Essential components of cell membranes Align themselves between water phase andlipid phase
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Phospholipids
bull Phospholipids (lecithin)ndash Are composed ofbull Glycerol backbonebull 2 fatty acidsbull Phosphatendash Are partially soluble in waterndash Are manufactured in our bodies so they arenot required in our diet
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Phospholipids1048708 At least one fatty acid and one phosphoruscompound attached to glycerol1048708 Includes lecithin (phosphotidylcholine) andsphingomyelins1048708 Synthesized by the body as needed
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Functions of phospholipids1048708 Are amphipathic so can act as emulsifiers1048708 Important component of cell membranes1048708 Present on the outer surface of lipoproteinsallowing them to float freely in the blood1048708 Especially important for insulation of nerves(in the myelin sheath as sphingomyelins)
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Sphingolipids
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Glycosphingolipids as determinants of bloodgroups
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Phospholipids
1- Glycerophospholipids
2-Sphingolipids
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Sphingolipidsbull Sphingosine is a derivative of glycerol but it has ndashNH2instead of -OH at C2 and has a -OH as well as a longchain hydrocarbon on C3bull The ndashNH2 forms an amide bond with a long chain FA toform a ceramidebull sphigomyelin is formed when a phosphodiester bridgelinks the C1 -OH of ceramide to ethanolamine or cholinebull Sphingomyelins are found abundantly in the myelinsheath that surrounds the nerve fibers
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Glycolipidsbull Glycolipids are lipids that contain carbohydratesbull Cerebrosides have a monosaccharide attached to theC1 -OH of ceramidebull Gangliosides have an oligosaccharide attached to theC1 -OH of ceramidebull Cerebrosides and gangliosides are found in the brainand nervous tissuebull In biomembranes glycolipids are orientedasymmetrically with the sugar units always on theextracellular side of the membrane
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Types of Fats(See figure 5-6)bull Saturated fats are composed of triglycerides in which most ofthe fatty acids are ldquosaturatedrdquondash Saturated fats are high in saturated fatty acids eg beef fatcheese milk fat butter etcndash Exceptions poultry and fish (less saturated)bull Unsaturated fatsMono and polyunsaturated fatsndash Most vegetable fats are high in polyunsaturated fatty acidseg corn oil safflower oil etcndash Exceptions coconut oil palm oilndash Coconut oil and palm oils are (also called tropical oils) highin saturated fatty acids
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Hydrogenation of fatty acids1048708 Process used to solidify an oil toincrease resistance to oxidationincrease shelf-life spreadabilityincreased smoke point1048708 Addition of H to C=C double bonds1048708 Formation of -trans fatty acids
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Minimize intake of trans- fatty acids1048708 Limit use of processed grain products1048708 Limit deep-fried foods1048708 Limit high fat baked goods1048708 Limit use of non-dairy creamers1048708 Ingredient to watch for partiallyhydrogenated vegetable oil
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Olive and canola oils are high inmonounsaturated fatty acidsbull Fish oils are high in ω3 PUFA
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Properties1048708 melting points of even-numberedcarbonfatty acids increase with chainlength and decrease according tounsaturation1048708 saturated long-chain fatty acids aresolid at body temperature (high meltingpoint)1048708 polyunsaturated fatty acids are liquid at0degC (low melting point)
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Which Ones Are Essential1048708 Linoleic acid (182 ω-6)1048708 Alpha-Linolenic acid (183 ω-3)1048708 Arachidonic acid (204 ω-6) (not)1048708 EPA (205 ω-3) (most likely)1048708 DHA (226 ω-3) (most likely)
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
1048708 Fatty acids can be saturated or unsaturated1048708 saturated fatty acids (SFA) contain themaximum amount of hydrogens possible - allC-C bonds are single1048708 monounsaturated fatty acids (MUFA) have 1point of unsaturation1048708 polyunsaturated fatty acids (PUFA) have 2 ormore points of unsaturation1048708 A variety of the three fatty acids are found infoods1048708 Foods high in SFA tend to be solid at roomtemperature MUFA tend to be solid atrefrigerator temps PUFA liquid at room andrefrigerator temps
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Fatty Acids1048708 Fatty acids are the simplest of the lipidscomponents of more complex lipids
1048708 Hydrocarbon chain with a methyl groupat one end and an acid group at theother end
1048708 Differ from each other in chain lengthand degree of saturation
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Sources1048708 Generally fats from fish andvegetables are less saturated fatsfrom animal products are moresaturated
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
The Role of Fatbull Essential fatty acidsndash Two fatty acids cannot be synthesized inthe body and must be obtained in the dietndash Alpha-linoleic acid (omega-3 fatty acid)bull Found in canola oil soybean oil flax seedand oil some nutsndash Linoleic acid (omega-6 fatty acid)bull Found in green leafy vegetables vegetableoils and whole grainsThe Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
The Role of Fatbull Essential fatty acidsndash Three fatty acids can be synthesized in thebody but may have to be obtained in thedietndash EPA and DHA (omega-3 fatty acid)bull Found in oily fish and fish oil supplementsndash Arachidonic acid (omega-6 fatty acid)bull Found in meats dairy eggs and poultry
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Essential Fatty Acidsbull Cannot be synthesized in the body must be providedfrom the dietbull Human body cannot make Linoleic acid (182)Linolenic acid (183)Humans do not have enzymes to make any of theomega-6 or omega-3 fatty acids from scratch nor canthey convert an omega-6 to omega-3 fatty acid or viceversabull Because these two fatty acids are indispensable to bodyfunction they must be supplied by the diet(Linoleic acid is omega 6 and Linolenic acid is an omega 3 fatty acid)
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Omega 3 fatty acids The first double bond is on C 3counting from the methyl end of the fatty acidEx linolenic acid (183)Omega 6 fatty acids The first double bond is on C 6counting from the methyl end of the fatty acidEx linoleic acid (182)The members of a given family or series have differentlengths and different number of double bonds but the first doublebond occurs at the same point
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Food Sources of Omega 3 Fatty Acids1 Linolenic acid18 carbon and 3 double bonds (18 3)Ex seeds nuts grains soybeans and veg oils2 Eicosapentaenoic Acid (EPA)20 carbons and 5 double bonds (205)Ex fish shellfish3 Docosahexaenonic Acid (DHA)22 carbons and 6 double bonds (226)Ex fish shellfish
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Sources of Essential FattyAcids1048708 Vegetable oils meats dairy eggs- ω6 fatty acids dominant1048708 Marine and seafood some vegetableoils- ω3 fatty acids dominant
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Common fatty acids and shorthand descriptionShort chain 4-8 C in milk fatButyric acid = 40 = ButanoicMedium chain 10-14 C in coconut palm kernelLauric acid = 120 = DodecanoicTypical 16-18 C in plants and animalPalmitic = 160 = hexadecanoicStearic = 180 = octadecanoicOleic =181 ω9 or 181 c9 = octadecenoicLinoleic = 182 ω6 or 182 c9 12 = octadecadienoicLinolenic = 183 ω3 or 183 c9 12 15 = octadecatrienoicLong chain 20-22 C in fish oilEPA = 205 ω3 = eicosapentaenoicDHA = 226 ω3 = docosahexaenoic
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Polyunsaturated Fatty Acids are EssentialFatty AcidsLinoleic (182Δ912) ω6Linolenic (183Δ91215) ω3Arachidonic (204Δ581114) ω6
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Systematic naming of International Union ofPure and Applied Chemistry (IUPAC)bull - ane ltlt - anoicbull - ene ltlt - enoicbull - diene triene tetraene ltlt - dienoic -trienoic tetraenoicbull omega (ω) counting from - CH3 end
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Chain length of fatty acids1048708 Long chain FA gt 12 carbons1048708 Medium chain FA 6 - 11 carbons1048708 Short chain FA lt 6 carbons1048708 can be released directly from theintestinal cell into the blood unlikelonger chain fatty acids1048708 Longer chain fatty acids tend to besolid at room temperature
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Lehninger 343
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Molecular biology of the cell 239
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
The degree of saturation of Fatty acids(a) Saturated fatty acids carry maximum of H atomsand have no double bondsEx Stearic acid (18 carbons no double bond or 180 )Palmitic acid has 16 Cs and no double bonds ( 160)(b) Monounsaturated fatty acids lost 2 H atoms andhave one double bondEx Oleic acid 18 C one double bond ( 181)(c) Polyunsaturated fatty acids(PUFA) two or moredouble bondsEx Linoleic(18 carbons 2 double bonds or 182)and linolenic) acid (183)
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Rule of thumb for determining degree of saturationfor fats isndash How hard the lipid is at room temperaturendash The more saturated a fat harder it is at roomtemperaturendash Vegetables and fish oils are liquid at roomtemperature (high in PUFA)ndash Most animal fats are solid at room temperature(high in saturated fatty acids) eg beef fat lardndash Polyunsaturated fats have lower melting pointdue to the carbon double bonds
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
The Location of Double BondsPoly unsaturated fatty acids also differ in the locationof double bondsThere are two families of polyunsaturated fatty acidsThese depend on the location of first double bond counting fromthe methyl end of the carbon chain1 Omega 3 (ω3)2 Omega 6 (ω6The Omega number indicates the position of the firstdouble bond in a fatty acid from the methyl (CH3) end ofthe fatty acid
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Triglyceridesbull Hydrogenation (Full and Partial) Theaddition of hydrogen atoms to unsaturatedfatty acidsndash Coverts liquid fats (oils) into a more solidformndash Used to create margarine from plant oilndash Partial often creates trans unsaturated fattyacidsndash Full creates saturated fatty acids
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
90 of dietary fat intake and 95 of fatstored in tissues Plant sources ndash high in polyunsaturated fattyacids (oils) Animal sources ndash high in saturated fatty acids(fats) Increased levels ndash increased risk forarteriosclerosis Indicated in blood by ldquocreamyrdquo plasma layer
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
Functions of triglycerides1048708 In the body1048708 Primary form of stored energy virtually unlimitedstorage1048708 adipose (fat) cells secrete hormones andsynthesizes enzymes that affect food intake andenergy use1048708 why isnrsquot glucose the primary storage form ofenergy1048708 Provide fuel for muscles during rest and lightactivity1048708 Insulation against shock and temperature extremes1048708 Contain fat-soluble vitamins and essential fattyacids
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
GlycerophospholipidsH2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O X
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O H
General Structure PA
PC PI45BP
Net ChargepH 7 = -1
Net ChargepH 7 = 0
Net ChargepH 7 = -4
G3P
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O CH2CH2N(CH3)2
H2C
HC
H2C
O
O
O
C(CH2)14CH3
C(CH2)7CH=CH(CH 2)7CH3
P
O
O
O
O-
O
H
H
OPO32-
OH
HH
OH
OPO32-H
HO H
- Slide 1
- Introduction
- در انتهاي درس دانشجويان بايستي قادر به پاسخ به سوالات زير باشند
- Slide 4
- Lipid Components
- Slide 6
- متعلقات
- Function of Fatty Acids
- Slide 9
- Nomenclature
- Slide 11
- متعلقات
- Slide 13
- Slide 14
- Fatty Acids
- ω 3 and ω6 Fatty acids
- Slide 17
- Palmitic acid
- Arachidonic acid
- Why are these essential
- Slide 21
- Slide 22
- Slide 23
- Slide 24
- Slide 25
- Slide 26
- Lipid peroxidation
- Slide 28
- Slide 29
- Slide 30
- Slide 31
- Sterol
- Sphingosine
- Classification of Lipids
- Slide 35
- Triglycerides
- Slide 37
- Slide 38
- Phospholipids
- General Structure of Glycerophospholipid
- Slide 41
- Slide 42
- Slide 43
- Phosphatidylcholine
- Therapeutic Uses
- Slide 46
- Slide 47
- Slide 48
- Ether Lipids (Plasmalogen [phosphatidal]amp Platelete activating factor [PAF])
- Slide 50
- Slide 51
- Slide 52
- Phosphatidyl Glycerol
- Slide 54
- Cardiolipin
- Slide 56
- Clinical significance
- Slide 58
- Phospholipases
- Slide 60
- Sphingolipids
- Slide 62
- Slide 63
- Sphingophospholipid Sphingomyelin
- Sphingoglycolipid Cerebrosides
- Gangliosides Complex Cerebroside
- Ganglioside
- Ganglioside nomenclature
- Slide 69
- Slide 70
- Gangliosidoses (Lipid Storage Diseases)
- Waxes
- Steroids
- Cholesterol
- Slide 75
- Cholesterol and cholesterol esters
- Slide 77
- Bile Acids
- Steroids Hormones
- Slide 80
- Progesterone
- Estradiol
- Cortisole
- Testosterone
- Aldosterone
- Calcitriol
- Vitamin D
- Eicosanoid Hormones
- Slide 89
- Eicosanoid
- Slide 91
- Slide 92
- Eicosanoid Hormones
- Slide 94
- Slide 95
- Effects of Prostaglandins
- NSAIDs (Non steroid anti-inflammatory drugs)
- Slide 98
- Selective COX inhibitors
- Slide 100
- Slide 101
- Physiological Function
- Functions of Apoproteins (Apo)
- Apoproteins of human lipoproteins
- Slide 105
- Classification of Lipoproteins
- The five classes of lipoprotein (all contain characteristic amounts TAG cholesterol cholesterol esters phospholipids and apoproteins)
- Slide 108
- Isoprenoids
- Slide 110
- Slide 111
- Slide 112
- Slide 113
- Slide 114
- Slide 115
- Slide 116
- Slide 117
- Slide 118
- Slide 119
- Slide 120
- Slide 121
- Slide 122
- Glycosphingolipids as determinants of blood groups
- Slide 124
- Phospholipids
- Slide 126
- Slide 127
- Slide 128
- Slide 129
- Slide 130
- Slide 131
- Slide 132
- Slide 133
- Slide 134
- Slide 135
- Slide 136
- Slide 137
- Slide 138
- The Role of Fat
- The Role of Fat
- Slide 141
- Slide 142
- Slide 143
- Slide 144
- Slide 145
- Slide 146
- Slide 147
- Slide 148
- Slide 149
- Slide 150
- Slide 151
- Slide 152
- Slide 153
- Slide 154
- Slide 155
- Slide 156
- Slide 157
- Slide 158
- Slide 159
- Slide 160
- Slide 161
- Slide 162
- Slide 163
- Slide 164
- Slide 165
- Slide 166
- Slide 167
- Slide 168
- Slide 169
- Glycerophospholipids
-
