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CHEMISTRY OF LIPIDSDefinition of lipids:
Lipids are heterogeneous group of compounds that are highly insoluble in water, but are
soluble in non-polar solvents like Benzene, Chloroform, ether, alcohol e.t.c.
Biological Roles of Lipids
Lipids perform several important functions
1. Lipids are the concentrated fuel reserves of the body (Triglycerides)
2. Lipids involves in the construction of all biological membranes.
3. Lipids are the sources of the fat soluble vitamins (A, D, E, K)
4. Some lipids acts as cellular metabolic regulators
(steroid hormones and prostaglandins)
5. Lipids act as the thermal insulators and maintain the body temperature
6. Lipids act as electrical insulators and help the neuronal transmissions.
7. Lipids make diet palatable (tasty)
CLASSIFICATION OF LIPIDS
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1. FATTY ACIDS
Fatty Acids are carboxylic acids with aliphatic hydrocarbon side chain.
These are the simplest Lipids.
Fatty acids mainly occur in the esterified form as major constituents of various lipids,
they are also present in free form
Based on presence of single or double covalent bonds fatty acids are divided in to
Saturated Fatty acids: Do not contain double bonds
Unsatur(ated Fatty acids: Contain double bonds
Mono unsaturated fatty acids: Contains one single double bond
Poly unsaturated fatty acids: Contains two or more double bonds
Numbering of carbon atoms in Fatty acids
There are different types of numbering systems
10 9 8 7 6 5 4 3 2 1 Delta numbering system
CH3CHCH =CH2CH2CH2CH2CH2CH2COOH
Greek letters
1 2 3 4 5 6 7 8 9 10 Omega numbering system
Counting carbons with Greek alphabets
The first CH2 adjacent to the carboxyl group is named as , and so on
The last carbon with CH3 group is called as omega () carbon
Delta ( ) system:
Carbons are numbered from COOH end to CH3
Carboxyl carbon (COOH) is counted as 1, and carbon with CH3 as the last
Above fatty acid is 10: 1 or 10:1;7
(Total 10 carbons: 1 double bond between 7&8 carbons)
Omega () system:
Carbons are numbered from CH3 to COOH
CH3 is counted as 1 and COOH as the last
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Above fatty acid is 10:17 (10 carbons: 1 double bond between 3&4carbons)
Length of Fatty acids:
Short chain fatty acids: with less than 6 carbons
Medium chain Fatty acids: with 8-14 carbons
Long chain Fatty acids: with 16-24 carbons
List of Important saturated fatty acids
Common name Numbering
Acetic acid 2:0
Propionic acid 3:0
Butyric Acid 4:0
Valeric Acid 5:0
Caproic acid 6:0
Capric acid 10:0
Palmitic acid 16:0
Stearic acid 18:0
Arachadic acid 20:0
List of Important Unsaturated Fatty acids
Common name ngmberig- girebmgn- Palmitoleic acid cis16: 1; 9 16:1 7
Oleic acid cis18:1;9 18:19
Linoleic acid All cis18: 2;9,12 18:2 6,9
Linolenic acid All cis18:3;9,12,15 18:3 3,6, 9
Arachidonic Acid All cis20:4; 5,8,11,14 20: 4 6,9,12,15
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Even and Odd Carbon Fatty acids:
Most of the fatty acids that occur in natural lipids are even carbons.
Most common even carbon fatty acids: Palmitic acid (16C) and Stearic acid (18C)
Most common odd carbon fatty acids: Propionic acid (3C) and valeric acid (5C)
Isomerism in unsaturated fatty acids
Unsaturated fatty acids shows geometric isomerism depending on the orientation of the
groups around the double bond
Cis configuration:
Similar groups are present on the same side of the double bond.
Trans configuration:
Similar groups are present on the opposite side of the double bond.
Essential fatty acids:
The fatty acids that cannot be synthesized by the body and therefore should be supplied
in the diet are known as essential fatty acids.
Essential fatty acids are chemically poly unsaturated fatty acids. They are
Linoleic aicd ( 18:2;9,12)
Linolenic acid( 18:3; 9,12,15)
Arachidonic acid (20:4;5,8,11,14) becomes essential when its precursor linoleic acid is
not supplied in diet.
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Essential fatty acids are present in vegetable oils, and fish oils
Functions of essential fatty acids:
Normal growth of the body
Formation of cell membrane
Transport of cholesterol
Formation of lipoproteins
Formation of eco sanoids
Protects against atherosclerosis
Non essential fatty acids: These can be synthesized by the body
These are saturated and mono unsaturated fatty acids
Synthesized from acetyl-CoA which is derived from glucose oxidation
2. SIMPLE LIPIDS
Esters of Fatty acids with alcohol
There are two types of simple lipids
i. Triacylglycerols (Fats & Oils), ii. Waxes
i. Triacylglycerols (Fats & Oils)
Esters of 3 fatty acids with a glycerol
COOH group of fatty acids condenses with OH of glycerol and forms ester link
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Triacylglycerol = 3 fatty acids are esterified to glycerol
Also known as Triglycerides and neutral fats
Insoluble in water and soluble in non-polar solvents
They are fuel reserves of animal, stored in the adipose tissue
The fat stored in normal men 20% women 25% of the body weight
Triglycerides are not found in biological membranes.
Triglyceride up on hydrolysis gives diacylglycerols and monoacylglycerols
Based on the type of fatty acids present triglycerides are divided in to
Simple triglycerides: Contains the same type of fatty acids at all the three carbons
Mixed triglycerides: Contains 2 or 3 different types of fatty acids
Mixed triglycerides are more common in nature.
Oil: triglyceride with one or more unsaturated fatty acids exists as liquid at room
temperature termed as oil
Plant triglycerides are having higher content of unsaturated fatty acids compared to thatof animals.
Hence animal fat will be solid and plant fat is liquid at room temperature
Properties of Triglycerides:
a) Hydrolysis:
Triglyceride +3 H2O Lipase 3 Fatty acids + Glycerol
This reaction helps the digestion and absorption of the fat from the intestine
Also helps the mobilization of fat from the adipose tissue.
b) Saponification:
Triglyceride + 3 NaOH 3 Fatty acidsNa (Soap) + Glycerol
The alkali can be sodium hydroxide (NaOH), or Potassium Hydroxide (KOH).
In the intestine soaps are formed with bile salts known as emulsification
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Emulsification process helps the easy absorption of fats from the intestine
c) Rancidity:
Oxidation of fat due to air, moisture, light, Bacteria is known as rancidity
Oxidation takes place at double bonds of the free fatty acids
Fats will be spoiled due to rancidity, the taste and smell will be unpleasant
Steps and types in rancidity
Hydrolytic rancidity:
Triglycerides are hydrolysed by bacterial lipase to produce glycerol + free fatty acids
Free fatty acids undergo further oxidative and ketonic rancidity.
Hydrolysis increases in presence of moisture and warm temperature
Oxidative rancidity: oxidation at double bonds forms peroxides
Ketonic rancidity: peroxidesat double bond decomposes to form aldehydes & ketones
Enhancers of rancidity:
Oxidizing agents like nascent oxygen (O), Pb2+
, Cu2+
, Fe2+
(Heme), Lipoxygenase
Detection of rancidity: Copper acetate reacts with free fatty acids
Prevention of rancidity:
Prevention of fat for the exposure to light and moisture
Addition of antioxidants like Vit-C, E and molecules withSH group (cystine)
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ii) Waxes: Esters of long chain fatty acids with long chain monohydric alcohols.
Eg: Bee wax, sebaceous secretion, cuticles of leaves
Waxes are not hydrolysed by lipase, hence animals cannot digest the wax
Waxes are solids at room temperature, highly hydrophobic
3. COMPLEX OR COMPOUND LIPIDS
Alcohol + Fatty acid + Some other molecule
There are three major types of complex (compound) lipids are present
i. Phospho Lipids ii. Glyco Lipids iii. Lipoproteins
They are further divided in to
i. Phospho Lipids
A) Glycero Phospho Lipids
a) Phosphatidic acid
b) Lecithin
c) Cephalin
d) Phosphotidyl Inositole) Phosphotidyl serine
f) Plasmalogen
g) Cardio Lipin
B) Phospho Sphingo lipids
a) Sphingomylin
ii. Glyco Lipids ( Glycosphingo lipids)
a) Cerebrosides
b) Gangliosides
iii. Lipoproteins
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i. Phospho Lipids: These lipids contain alcohol + Fatty acids + phosphoric acid.
There are two classes of phospho lipids
A) Glycerophospholipids (Phosphoglycerides): contain glycerol as the alcohol
B) Sphingophospholipids: Contains shingosine as the alcohol.
A) Glycerophospholipids (Phosphoglycerides):
a) Phosphatidic acid:
Glycerol esterified with a
Saturated fatty acid at carbon 1,
Unsaturated fatty acid at its carbon 2
Phosphoric acid at carbon 3
b) Lecithins ( Phosphotidyl Choline)
Choline attached to phosphate of phosphatidic acid
Carbon:1 = Saturated fatty acid
Carbon: 2 = Unsaturated fatty acid
Carbon 3: phosphoric acid + choline
Functions of lecithin
Construction of cell membrane Formation of lecithin cholesterol esters
Lecithin + Cholesterol
Lecithin cholesterol acyltransferase (LCAT)
Cholesterol ester (Cholesterol-Fatty acid) + Lysolecithin
Cholesterol esters are taken to liver, mixed in bile and excreted
Absence of lecithin increases cholesterol in the blood, leads to atherosclerosis
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Lecithin in bile prevents formation of gall stones (cholesterolstones) Storage of choline: lecithin acts as store for choline
Choline involves in neurotransmissions (forms acetyl choline)
Choline prevents accumulation of fat in liver (lipotropicfactor)
Choline gives methyl group for methylation reactions
Dipalmitoyl lecithin: Is a surfactant (decreases surfacetension)found in lungs and prevents the adherence of inner surfaces of lungs due to the
surface tension
dipalmitoyl lecithin is less produced in premature infants causing respiratory failure
this condition is known as respiratory distress syndrome.
c) Cephalin ( Phosphotidyl Ethanolamine):
Ethanolamine attached to phosphatidic acid is termed as cephalin or phosphatidyl
ethanolamine
Involves in blood coagulation mechanism
d) Lipositol (Phosphotidyl Inositol) : Inositol attached to the phosphatidic acid.
This is an important component of cell membranes.
Acts as a second messenger in Ca2+
dependent hormonal actions
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e) phosphotidyl Serine The aminoacid serine is attached to phosphatidic acid
found in brain, blood and other tissues
f) Plasmalogens
Fatty aldehyde attached at C1 of glycerophospholipids by ether link known as
plasmalogens.
Lecithin with fatty aldehyde at C1 = phosphatidal choline
Cephalin with fatty aldehyde at C1 = phosphatidal ethanolamine
Present in brain and muscle
g) Cardiolipin: Two molecules of phosphotidic acids attached to a glycerol through
their phosphoric acid groups is called cardiolipin.
Cardiolipin is an important component of inner mitochndrial membrane.
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B) Sphingo Phospho Lipids:
Sphingo lipids contain sphingosine as alcohol, they do not contain glycerol
Sphingo lipids are found in brain and nervous tissue.
a) Ceramide: Fatty acid + Sphingosine
Fatty acid attached to Sphingosine through
amide link in ceramide
b) Sphingomyelin: Fatty acid+ Sphingosine+ Phosphric acid+ Choline
Choline is attached to the phosphate of ceramide through ester link
Present in nervous tissue and brain
Niemann picks disease
Accumulation of sphingomyelin in liver,spleen and brain
Caused by the deficiency of an enzyme sphingomyelinase
Clinical findings are enlargement of liver & spleen, and mental retardation
Functions of Phospholipids:
Construction of cell membranes and regulates the cell permeability.
Helps the absorption of fat from the intestine,
Involves in the synthesis of lipoproteins
Acts as surfactants, eg: Dipalmitoyl lecithin in lungs.
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Prevents the accumulation of fat in liver
Involves in cholesterol metabolism
Cephalin participates in blood clotting.
Phosphatidyl inositol participates in signal transduction across the cell membrane.
ii. Glycolipids:
Present in cell membranes and nervous tissue,
Contains sphingosine + fatty caid + carbohydrate,
There are two important classes of glycolipids.
a) Cerebrosides b) Gagliosides
a) Cerebrosides:
These are the simplest glycolipids contains
Sphingosine + Fatty acid (ceramide) + sugar (galctose or glucose).
Present in brain, nervous tissue
Acts as insulators for neurotransmissions
Gauchers disease:
Cerebrosides accumulate in liver, spleen and bone marrow.
Because of the deficiency ofenzyme glucocerebrosidase
Spleen and liver will be enlarged
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b) Gangliosides: These are complex glycosphingolipids
Ceramide attached to N-acetyl neuramnic acid (sialic acid) and other mono saccharides.
The important gangliosides present in the brain are GM1, GM2, GD, GT
Also present in membrane receptors
Where: G= Ganglioside; M= Mono sialic acid residue
D= Di sialic acid residues T=Tri sialic acid residues
Tay sachs disease: accumulation of GM2 gangliosides in brain, spleen
Because of deficiency of an enzyme hexosaminidase A
Leads to mental retardation, blindness and muscular weakness
iii. Lipoproteins: = Lipid + apolipoprotein
Lipids combined with proteins are termed as lipoproteins
The proteins present in lipoproteins are known as apolipoproteins
Apolipoproteins are mostly globulins in nature
Lipids present in lipoproteins are triglycerides, phospholipids, cholesterol, cholesterol
esters and free fatty acids
Lipoprotein helps the transport of lipids in the blood, and in and out of the cells
Lipoproteins involves in the construction of cell membrane
If lipid concentration increases the density of lipoprotein decreases
If the lipid concentration decreases the density of lipoprotein increases
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Classification of lipoproteins based on centrifugation
Lipoproteins can be separated by centrifugation based on their relative densities
They are mainly divided in to 4 classes
Type Lipids present Important
Apolipoproteins present
Chylomicrons Triglycerides apo-A-I,A-II,C-I,C-II
VLDL Triglycerides, cholesterol apo-B-100,C-I,C-II,E
IDL Less TG & cholesterol apo-B-100,C-I, C-II,E
LDL Cholesterol
Cholesterol esters
Phospholipids
apo-B-100,C-I, C-II,E
HDL Cholesterol
Cholesterol esters
Phospholipids
apo- A-I, A-II,E,D
Free fatty acids-Albumin Free fatty acids Albumin
Functions of apo-lipoproteins
Transport of lipids (gives hydrophilic covering for lipids)
Binds membrane receptors
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Regulates enzyme activities (Activates /inhibits)
Electrophoretic separation of lipoproteins
Proteins present in the lipoproteins shows charge (ve & +ve)
During electrophoresis lipoproteins will separate based on their charge
4. DERIVED LIPIDS
Hydrolysis or chemical modification of simple or complex lipids gives derived lipids
Some of important derived lipids are
Fatty acids
Ecosanoids
Glycerol
Steroids & Sterols (Cholesterol, Vitamin-D, Bile acids & Salts, Sex hormones)
Separation
basedo
n
density
Centrifugation Electrophoresis
Separation
basedo
n
charge
CM CM
VLDL LDL ( lipoproteins)
LDL VLDL (pre lipoproteins)
HDL HDL ( lipoproteins)
FFA-albumin Free fatty acids-Albumin +
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i) ECOSANOIDS
Cyclic compounds that are derived from arachidonic acid (20 C poly unsaturated)
Note: Ecosa = 20
Ecosanoids acts like local hormones
They are derived in to two types
A) Prostanoids
Prostaglandins (PG)
Prostacyclines (PGI)
Thromboxanes (Tx)
B) Leukotriens (LT)
A) Prostanoids
a) Prostaglandins
There are four main groups of prostaglandins are present A, B, E, and F
Recently some more groups are identified like, C,D,H,G,I,X
Causes vasodilatation, and contraction of uterus & intestine,
b) Prostacyclines
Causes vasodilatation
Prevents platelet aggregation
c) Thromboxanes
Causes vasoconstriction
Enhances platelet aggregation
B) Leukotriens
Are present in leukocytes
Causes chemo taxis of leukocytes towards the site of inflammation
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a)Cholesterol:
Structure:
Steroid nucleus attached with an aliphatic side chain at carbon 17
Aliphatic side chain contains 8 carbons; hence cholesterol contains total 27 carbons
Hydroxyl group (-OH) is present at carbon 3
Double bond between carbons 5-6
Cholesterol contains five methyl (CH3) groups ( C18, C19, C21, C26, C27).
Properties and functions of cholesterol
Cholesterol is a yellowish crystalline solid in nature Cholesterol is the most abundant animal sterolCholesterol is found only in animals.
Cholesterol is present cell membranes (increases fluidity of cell membrane)
Cholesterol is a poor conductor of heat and electricity hence functions as insulator for
nervous tissue.
Cholesterol involves in the synthesis of Bile acids, steroid hormones and Vitamin-D.
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b) Vitamin D: Is synthesized from cholesterol in animals
Ergosterol (Fungi) Cholesterol (Animals)
U.V light U.V light (In skin)
Vitamin D2 (ergocalciferol) Vitamin D3 (cholecalciferol)
By enzyme 25,Hydroxylase
in Intestine
25,hydroxy cholecalciferol (Calcidiol)
1- Hydroxylase
in Kidneys
1,25 dihydroxy cholecalciferol (Clacitriol) is the active form of vitamin-D
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Bile salts: Sodium salts of conjugated bile acids
Eg: sodium glycocholate, Sodium tauro cholate
Functions of bile salts
Helps in digestion and absorption of lipids from the intestine (emulsification)
Stimulates liver to secrete more bile (choleretic effect)
Prevents formation of cholesterol stones
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d) Steroid Hormones:
There are two major classes of steroid hormones
All the steroid hormones are derived from cholesterol
i) Sex Hormones:
a) Estrogens (Female sex hormones)
Estrone Estradiol Estriolb) Progestins (Female sex hormones)
Progesteronc) Androgens (Male sex hormones)
Testosterone Dihydrotestosterone
ii) Adrinocortical hormones
a) Gluco corticoids
Corticosterone Cortisol Dehydrocorticosterone Cortisoneb) Mineralo corticoids
Aldosterone 11-deoxy corticosterone
i) Sex hormones:
a) Estrogen: Is a female sex hormone
There are three types of estrogens Estrone (E1), Estradiol (E2), Estriol (E3)
Estradiol (E2) is the most active estrogen
Structure:
Ring A is unsaturated
-OH group at C3
Hydroxyl group at C17
Methyl group (C18) at C13
Site of production:
Females: Ovary, Placenta, Adrenal cortex (minor amounts)
Males: Testes, Adrenal cortex (minor amounts)
Functions: Development of female secondary sexual characters
Anabolic effect on bones and cartilage
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Stimulates spermatogenesis, Shows anabolic effect on proteins
ii. Adrenal cortical hormones:
Adrenal cortical hormones are mainly divided in to two types
Are produced from adrenal cortex
a) Glucocorticoids: Corticosterone, Dehydrocorticosterone, Cortisol , Cortisone
They regulates the carbohydrates, Fat and protein metabolisms
Shows catabolic effect on fat and protein metabolisms
Shows anabolic effect on carbohydrate metabolism
b) Mineralcorticoids: Aldosterone, 11-deoxy corticosterone
Regulates the mineral metabolism
Acts on kidneys stimulates secretion of K+, H
+and reabsorption of Na
+
All adrenal cortical hormones are derived by slight modifications of corticosterone
Corticosterone structure
Keotne group at C3
Double bond between C4& C5
-OH at C11
Methyl groups at C10,C13
Ketol group at C17
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5. FREE RADICALS AND ANTIOXIDANTS
Free Radical:
a molecule or atom that contains one or more unpaired electrons, and is capable of
independent existence.
Different types of free radicals produced in the body
O (singlet oxygen / nascent oxygen)
O2-
(Super Oxide radical)
OH-
( Hydroxyl Radical)
HOO-
( Hydro Peroxy Radical)
ROO-
(Lipid Peroxy Radical)
Free radicals are formed during the normal metabolism in presence of oxygen or metal
ions ( Cu++
, Fe++
) they are highly reactive.
Free radicals can generate new free radicals by chain reaction
Free radicals damages the cell membranes and biomolecules
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Antioxidants:
The molecules that can stop or slow down the oxidation of lipids and other
biomolecules are termed as anti oxidants.
i) Natural anti oxidants: These are of two types:
a) Preventive antioxidants:
Reduces the rate of chain initiation (first step of lipid peroxidation)
Eg: Catalase, Glutathione peroxidase, selenium
EDTA( Ethylene Diamine Tetra Acetate)
DTPA ( Diethylene Triamine Penta Acetate)
b) Chain Breaking Anti Oxidants:
They stops the chain elongation, (second step of the lipid peroxidation)
eg: Super oxide desmutase ( SOD)
Vitamin-E, Vitamin-C
ii. Artificial antioxidants : These are chemically synthesized
Added in lipid based foods to prevent the oxidation of lipids ( Rancidity) in the food.
Eg: Propyl Gallate,
Butylated Hydroxy anisole (BHA)
Butylated Hydroxy Toluene (BHT)