Lecture 5 - Lipids
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Transcript of Lecture 5 - Lipids
Introduction• Definition: water insoluble compounds
• Most lipids are fatty acids or ester of fatty acid• They are soluble in non-polar solvents such as petroleum
ether, benzene, chloroform
• Functions• Energy storage• Structure of cell membranes• Thermal blanket and cushion• Precursors of hormones (steroids and prostaglandins)
• Types:• Fatty acids• Neutral lipids• Phospholipids and other lipids
Fatty acids• Carboxylic acid derivatives of long chain
hydrocarbons– Nomenclature (somewhat confusing)
• Stearate – stearic acid – C18:0 – n-octadecanoic acid
– General structure:
(CH2)nCH3 COOH
n is almost always even
n = 0 : CH3COOH n = 1 : propionic acid
Fatty acids
• Common fatty acidsn = 4 butyric acid (butanoic acid)n = 6 caproic acid (hexanoic acid)n = 8 caprylic acid (octanoic acid)n = 10 capric acid (decanoic acid)
Fatty acids
• common FA’s: n = 12: lauric acid (n-dodecanoic acid; C12:0)n = 14: myristic acid (n-tetradecanoic acid; C14:0)
n = 16: palmitic acid (n-hexadecanoic acid; C16:0)
n = 18; stearic acid (n-octadecanoic acid; C18:0)
n = 20; arachidic (eicosanoic acid; C20:0)
n= 22; behenic acidn = 24; lignoceric acidn = 26; cerotic acid
Types of Lipids
• Lipids with fatty acidsWaxesFats and oils (trigycerides)PhospholipidsSphingolipids
• Lipids without fatty acidsSteroids
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Fatty Acids
• Long-chain carboxylic acids• Insoluble in water• Typically 12-18 carbon atoms (even number)• Some contain double bonds
corn oil contains 86% unsaturated fatty acids and
14% saturated fatty acids
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Fatty acids
• Fatty acids can be classified either as:– saturated or unsaturated– according to chain length:
• short chain FA: 2-4 carbon atoms• medium chain FA: 6 –10 carbon atoms• long chain FA: 12 – 26 carbon atoms• essential fatty acids vs those that can be biosynthesized
in the body:– linoleic and linolenic are two examples of essential fatty acid
Saturated and Unsaturated Fatty Acids
Saturated = C–C bondsUnsaturated = one or more C=C bonds
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COOH
COOH
palmitoleic acid, an unsaturated fatty acid
palmitic acid, a saturated acid
Structures
Saturated fatty acids• Fit closely in regular pattern
Unsaturated fatty acids• Cis double bonds
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COOHCOOHCOOH
C CH H
COOHcis double bond
Properties of SaturatedFatty Acids
• Contain only single C–C bonds
• Closely packed
• Strong attractions between chains
• High melting points
• Solids at room temperature
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Properties of UnsaturatedFatty Acids
• Contain one or more double C=C bonds• Nonlinear chains do not allow molecules to pack
closely• Few interactions between chains• Low melting points• Liquids at room temperature
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Stearic acid is saturated and would have a higher melting point than the unsaturated fatty acids.
Linoleic has two double bonds, it would have a lower mp than oleic acid, which has one double bond.
stearic acid mp 69°Coleic acid mp 13°C
linoleic acid mp -17°C
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Neutral lipids
• Glycerides (fats and oils) ; glycerides– Glycerol
– Ester of glycerol - mono glycerides, diglycerides and triglycerides
• Waxes – simple esters of long chain alcohols
CH2OH
CH2OH
OHH OH
OH
OH
glycerol is a prochiral molecule
GLYCERIDES
O
OH
OH
R
O
O
OH
O
R
O
R
O
O
O
R
O
R
O
OR
O
MONOGLYCERIDE DIGLYCERIDE TRIGLYCERIDE
Function: storage of energy in compact form and cushioning
Fats and Oils
Formed from glycerol and fatty acids
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+
HO C (CH2)14CH3
O
HO C (CH2)14CH3
O
HO C (CH2)14CH3
O
glycerol palmitic acid (a fatty acid)
CH
CH2 OH
OH
CH2 OH
Triglycerides (triacylglcerols)
Esters of glycerol and fatty acids
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CH
CH2
CH2 O
O
O
C (CH2)14CH3
O
C (CH2)14CH3
O
C (CH2)14CH3
O
ester bonds
+
+
+
H2O
H2O
H2O
Stereospecific numbering
• Carbon 2 of triglycerides is frequently asymmetric since C-1 and C-3 may be substituted with different acyl groups
• By convention we normally draw the hydroxyl group at C-2 to the left and use the designation of sn2 for that particular substituent
• C-1 and C-3 of the glycerol molecule become sn1 and sn3 respectively
Fatty acid reactions
• salt formation
• ester formation
• lipid peroxidation
RCO2H RCO2-Na+NaOH
(a soap)
R'OH + RCO2H RCO2R'-H20
R
R'
H H
R R'
OOH
O2
non-enzymatic
very reactive
Lipid peroxidation
• a non-enzymatic reaction catalyzed by oxygen• may occur in tissues or in foods (spoilage)
– the hydroperoxide formed is very reactive and leads to the formation of free radicals which oxidize protein and/or DNA (causes aging and cancer)
• principle is also used in drying oils (linseed, tung, walnut) to form hard films
Properties of Triglycerides
Hydrogenation• Unsaturated compounds react with H2
• Ni or Pt catalyst• C=C bonds C–C bonds
Hydrolysis• Split by water and acid or enzyme catalyst• Produce glycerol and 3 fatty acids
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Hydrogenated fats
• hydrogenation leads to either saturated fats and or trans fatty acids
• the purpose of hydrogenation is to make the oil/fat more stable to oxygen and temperature variation (increase shelf life)
• example of hydrogenated fats: Crisco, margarine
Hydrogenation
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CH
CH2
CH2 O
O
O
C
O
(CH2)5CH CH(CH2)7CH3
C
O
(CH2)5CH CH(CH2)7CH3
C
O
+
(CH2)5CH CH(CH2)7CH3
H23Ni
Product of Hydrogenation
Hydrogenation converts double bonds in oils to single bonds. The solid products are used to make margarine and other hydrogenated items.
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CH
CH2
CH2 O
O
O
C (CH2)14CH3
O
C (CH2)14CH3
O
C (CH2)14CH3
O
Hydrolysis
Triglycerides split into glycerol and three fatty acids (H+ or enzyme catalyst)
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CH
CH2
CH2 O
O
O
C (CH2)14CH3
O
C (CH2)14CH3
O
C (CH2)14CH3
O H2O+3
3+ HO C (CH2)14CH3
O
CH
CH2 OH
OH
CH2 OH
H+
Saponification and Soap
• Hydrolysis with a strong base• Triglycerides split into glycerol and the salts of fatty
acids • The salts of fatty acids are “soaps”• KOH gives softer soaps
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Saponification
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3+ Na+ -O C (CH2)14CH3
O
CH
CH2 OH
OH
CH2 OH
CH
CH2
CH2 O
O
O
C (CH2)16CH3
O
C
O
(CH2)16CH3
(CH2)16CH3C
O
+ 3 NaOH
salts of fatty acids (soaps)
Analytical methods to evaluate lipids
• saponification number• iodine value (Hanus method)• free fatty acids• acetyl number• Reichert-Meissl number• HPLC/GC (for more precise analysis)
Saponification number
• gives some clue as to the average size of fatty acids in a given sample of fat
• defined as the number of milligrams of KOH needed to neutralize the fatty acids in 1 Gm of fat
• butter (large proportion of short chain FAs) sap. no. 220 – 230
• oleomargarine (long chain FAs) sap. No is 195 or less
Iodine number
• measures the degree of unsaturation in a given amount of fat or oil
• the iodine number is the number of grams of iodine absorbed by 100 grams of fat
• Cottonseed oil: 103 –111• Olive oil: 79 – 88• Linseed oil: 175 –202
• frequently used to determine adulteration of commercial lots of oils
HHI I
HHI2
Acetyl number• some fatty acids have hydroxyl groups
(CH2)21H3C CH
OH
COOH
cerebronic acid
(CH2)5H3C CH CH2
OH
CH CH (CH2)7 COOH
ricinoleic acid
The acetyl number gives the proportion of these hydroxyl-containing fatty acids in a given sample of fat or oil
fatty acid
OH
acetic anhydridefatty acid
O C
O
CH3
fatty acid
OH
+
COOHH3C
titrate with standardizedKOH
acetylated fatty acid
Acetyl number
• the acetyl number is the number of milligrams of KOH needed to neutralize the acetic acid of 1 Gm of acetylated fat– examples:
• castor oil – 146 –150• cod liver oil – 1.1• cottonseed oil – 21 – 25• olive oil – 10.5• peanut oil – 3.5
Reichert – Meissl number
• Measures the amount of volatile fatty acids (low MW and water soluble FAs)
• R-M number is the number of milliliters of 0.1N alkali required to neutralize the soluble fatty acids distilled from 5 Gm of fat
• Butter fat has a high R-M number
WAXES• simple esters of fatty acids (usually saturated with long
chain monohydric alcohols)
H3C (CH2)14 C
O
O CH2 (CH2)28-CH3
long chain alcohol
fatty acid
Beeswax – also includes some free alcohol and fatty acidsSpermaceti – contains cetyl palmitate (from whale oil) –useful forPharmaceuticals (creams/ointments; tableting and granulation)Carnauba wax – from a palm tree from brazil – a hard wax used oncars and boats
Waxes
(CH2)14H3C CH2-OH cetyl alcohol
(CH2)24H3C CH2-OH hexacosanol
(CH2)28H3C CH2-OH triacontanol (myricyl alcohol)
Examples of long chain monohydric alcohols found in waxes
Phospholipids
• the major components of cell membranes– phosphoglycerides
O R
O R'
O
P
O
O
O
O-
X
Ofatty acids (hydrophobic tail)
glycerol
phosphate
Phospholipids are generally composed of FAs, a nitrogenous base, phosphoricacid and either glycerol, inositol or sphingosine
O R
O R'
O
P
O
O
O
O-
X
Ofatty acids (hydrophobic tail)
glycerol
phosphate
X = H (phosphatidic acid) - precursor to other phospholipids
X = CH2-CH2-N+(CH3)3 phosphatidyl choline
X = CH2-CH(COO-)NH3+ phosphatidyl serine
X = CH2-CH2-NH3+ phosphatidyl ethanolamine
Sphingolipids
OH
NH2
OH
NH2
OH
HO R long chain hydrocarbon
attach fatty acid here
attach polar head group here
sphingosine
Based on sphingosine instead of glycerol
Sphingomyelin
NH
O
HO R
PO
O-
O
N(CH3)+
R'
O
usually palmitic acid
phosphatidyl choline (also can be ethanolamine)
Ether glycerophospholipids
• Possess an ether linkage instead of an acyl group at the C-1 position of glycerol– PAF ( platelet activating factor)
– A potent mediator in inflammation, allergic response and in shock (also responsible for asthma-like symptoms)
– Plasmalogens: cis ,-unsaturated ethers
Ether glycerophospholipids
H2C CH
O
CH2
O
O
P
O
-O O
C O
CH3
CH2 CH2 N
CH3
CH3
CH3
platelet activating factor or PAF
H2C CH
O
CH2
O
O
P
O
-O O
C O
CH2 CH2 N
CH3
CH3
CH3
A choline plasmalogen
H
H
glycolipids
NH
O
HO R
R'
O
SUGAR polar head is a sugar
beta linkage
There are different types of glycolipids: cerebrosides, gangliosides,lactosylceramides
GLYCOLIPIDSGLYCOLIPIDS• Cerebrosides
• One sugar molecule– Galactocerebroside – in neuronal membranes– Glucocerebrosides – elsewhere in the body
• Sulfatides or sulfogalactocerebrosides• A sulfuric acid ester of galactocerebroside
• Globosides: ceramide oligosaccharides• Lactosylceramide
– 2 sugars ( eg. lactose)
• Gangliosides• Have a more complex oligosaccharide attached• Biological functions: cell-cell recognition; receptors for
hormones
Gangliosides
• complex glycosphingolipids that consist of a ceramide backbone with 3 or more sugars esterified,one of these being a sialic acid such as N-acetylneuraminic acid
• common gangliosides: GM1, GM2, GM3, GD1a, GD1b, GT1a, GT1b, Gq1b
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)
Cardiolipids
C
H2C O
O
H2C O P
O
OH
O
C
O
R1
C
O
R2
CH2 C
OH
H
CH2 O P O
OH
O
CH2
C OH
CH2O
C
O
R3
C
O
R4
H
glycerolglycerol
glycerol
A polyglycerol phospholipid; makes up 15% of total lipid-phosphoruscontent of the myocardium – associated with the cell membrane
Cardiolipids are antigenic and as such are used in serologic test forsyphilis (Wasserman test)
Sulfolipids
• also called sulfatides or cerebroside sulfates• contained in brain lipids• sulfate esters of cerebrosides• present in low levels in liver, lung, kidney,
spleen, skeletal muscle and heart• function is not established
Lipid storage diseases
• also known as sphingolipidoses• genetically acquired• due to the deficiency or absence of a catabolic
enzyme• examples:
• Tay Sachs disease• Gaucher’s disease• Niemann-Pick disease• Fabry’s disease
Blood groups
• determined by various glycolipids on RBCs
• A antigens
• B antigens
• H antigens
AcN Gal
L-Fucose
AcN Glu-sphingosine
Gal Gal NAc-Glu-sphingosine
L-Fucose
Gal NAc--Glu-sphingosine
L-Fucose
not recognized by anti-A or anti-B antibodies
(found on type O blood cells)
Cholesterol and cholesterol esters
CH3
CH3
H
OH
H3C
HH
hydrophillic
hydrophobic
R
O
usually palmitate
drawn this way
Cholesterol sources, biosynthesis and degradation
• diet: only found in animal fat• biosynthesis: primarily synthesized in the liver from acetyl-
coA; biosynthesis is inhibited by LDL uptake• degradation: only occurs in the liver
Cholesterol and cholesterol esters
HO
HH
Functions: -serves as a component of membranes of cells (increases or moderates membrane fluidity -precursor to steroid hormones -storage and transport – cholesterol esters
Prostaglandins and other eicosanoids
• local hormones, unstable, key mediators of inflammation
• derivatives of prostanoic acid
COOH
20
8
12
prostanoic acid
Functions of eicosanoids
• Prostaglandins – particularly PGE1 – block gastric production and thus are gastric protection agents
• Misoprostol (Cytotec) is a stable PGE1 analog that is used to prevent ulceration by long term NSAID treatment
• PGE1 also has vasodilator effects– Alprostadil (PGE1) – used to treat infants with congenital
heart defects– Also used in impotance (Muse)
C5H11
H S
Cys
gGlu
OH
COOH
LEUKOTRIENE F4 (LTF4)
C5H11
H S
Cys
OH
COOH
Gly
gGlu
LEUKOTRIENE C4 (LTC4)
Leukotrienes are derived from arachidonic acid via the enzyme 5-lipoxygenase which converts arachidonic acid to 5-HPETE (5-hydroperoxyeicosatetranoic acid) and subsequently bydehydration to LTA4
peptidoleukotrienes
Leukotrienes
Lipid-linked proteins
• Lipid-linked proteins (different from lipoproteins)– lipoproteins that have lipids covalently attached to
them– these proteins are peripheral membrane proteins
Lipid-linked proteins
• 3 types are most common:– Prenylated proteins
• Farnesylated proteins (C15 isoprene unit)• Geranylgeranylated proteins (C20 isoprene unit)
– Fatty acylated proteins• Myristoylated proteins (C14)• Palmitoylated proteins (C16)
Lipid-linked proteins
• glycosylphosphatidylinositol-linked proteins (GPI-linked proteins)– occur in all eukaryotes, but are particularly
abundant in parasitic protozoa– located only on the exterior surface of the plasma
membrane
Lipoproteins
• particles found in plasma that transport lipids including cholesterol
• lipoprotein classes• chylomicrons: take lipids from small intestine through
lymph cells• very low density lipoproteins (VLDL)• intermediate density lipoproteins (IDL)• low density lipoproteins (LDL)• high density lipoproteins (HDL)
Lipoprotein class
Density (g/mL)
Diameter (nm)
Protein % of dry wt
Phospholipid %
Triacylglycerol % of dry wt
HDL 1.063-1.21 5 – 15 33 29 8
LDL 1.019 – 1.063
18 – 28 25 21 4
IDL 1.006-1.019 25 - 50 18 22 31
VLDL 0.95 – 1.006 30 - 80 10 18 50
chylomicrons < 0.95 100 - 500 1 - 2 7 84
Composition and properties of human lipoproteins
most proteins have densities of about 1.3 – 1.4 g/mL and lipid aggregates usuallyhave densities of about 0.8 g/mL