Neutral fats or triacylglycerol or triglycerides

These are esters of fatty acids with alcohol glycerol,

Lipids are a major source of energy for the body
e.g. tripalmitin. Because they are uncharged, they are
besides their various other biochemical function and
termed as neutral fat. The fat we eat are mostly
their role in cellular structure. Lipids are a
triglycerides. A fat in liquid state is called an oil, e.g.
heterogenous group of water insoluble (hydrophobic)
vegetable oils like groundnut oil, mustard oil, corn oil,
organic molecules. Lipids include fats, oils, steroids,
etc.
waxes and related compounds.
This chapter introduces the chemistry and Waxes
functions of lipids. True waxes
These are esters of fatty acids with higher molecular
DEFINITION, CLASSIFICATION AND weight monohydric long chain alcohols. These
FUNCTIONS OF LIPIDS compounds have no importance as far as human
metabolism is concerned. For example,
Definition of Lipids Lanolin (from larnb's wool) Bees—wax
Lipids may be defined as organic substances insoluble

Spermacetic oil (from whales).

in water but soluble in organic solvents like These are widely used in pharmaceutical, cosmetic
chloroform, ether and benzene. They are esters of fatty and other industries in the manufacture of lotions,
acids with ointments and polishes.
alcohol esters and are utilizable by the living organism.
Other waxes
Classification of Lipids These are esters of fatty acid with alcohol, e.g.
There are many different methods of classifying lipids. Cholesterol forms cholesterol ester
The most commonly used classification of lipids is Retinol (vitamin A) forms vitamin A ester
modified from Bloor as follows: Cholecalciferol (vitamin D) forms vitamin D ester.
1. Simple lipids
2. Complex or compound lipids Complex or Compound Lipids
3. Derived lipids. These are esters of fatty acids, with alcohol containing
Simple Lipids additional (prosthetic) groups. These are subclassified
These are esters of fatty acids with various according to the type of prosthetic group present in the
alcohols. Depending on the type of alcohols, these lipid as follows:
are sub- 1. Phospholipids
2. Glycolipids
classified as: 1. Neutral fats or triacylglycerol or 3. Lipoproteins.
triglycerides Phospholipids
2. Waxes.
28 ESSENTIALS OF BIOCHEMISTRY

Lipids containing, in addition to fatty acids and an Functions of Lipids

alcohol, a phosphoric acid residue. They also have
nitrogen containing bases and other substituents. Lipids serve as:
Phospholipids may be classified on the basis of the Storage form of energy: The fats and oils are used
type of alcohol present in them as: almost universally as stored forms of energy in
Glycerophospholipids
living organisms.
Sphingophospholipids.
Structural Lipids: Lipids are major structural
Glycerophospholipids components of membranes, e.g. phospholipids,
The alcohol present is glycerol. Examples of glycolipids and sterols.
glycerophospholipids are: Cholesterol, a sterol, is a precursor of many steroid
' Phosphatidyl choline (lecithin) hormones, vitamin D and is also an important
' Phosphatidyl ethenolamine (cephalin) Phosphatidyl component of plasma membrane.
serine Lipid acts as a thermal insulator in the subcutaneous
' Phosphatidyl inositol tissues and around certain organs.
' Lysophospholipid Nonpolar lipids act as electrical insulators in
Plasmalogens Cardiolipins. neurons.
Sphingophospholipids Lipids are important dietary constituents because of
The alcohol present is sphingosine, e.g. the fat soluble vitarnins and essential fatty acids
Sphingomyelins. which are present in the fat of natural foods. Lipids
Glycolipids help in absorption of fat soluble vitarnins (A,D,E
Lipids containing fatty acid, alcohol sphingosine and and K). They act as a solvent for the transport of fat
additional residue are carbohydrates with nitrogen base. soluble vitamins.
They do not contain phosphate group. These sugar
containing sphingolipids are also called glycosphingo
Fatty acids are carboxylic acids with hydrocarbon
lipids. For example: chains and represented by a
Cerebrosides Gangliosides. chemical formula R-COOH, where R stands for
Lipoproteins hydrocarbon chain. The fatty acids are amphipathic
Lipoproteins are formed by combination of lipid with a in nature, i.e. each has hydrophilic (COOH) and
prosthetic group protein, e.g. serum lipoproteins like: hydrophobic (hydrocarbon chain) groups in the
Chylomicrons structure.
Very low density lipoprotein (VLDL) Low density
lipoprotein (LDL)
High density lipoprotein (HDL).
Derived Lipids
Derived lipids include the products obtained after the
hydrolysis of simple and compound lipids which
possess the characteristics of lipids, e.g.
Fatty acids
Steroids
Cholesterol
Lipid soluble vitamins and hormones Ketone
bodies.
 CHEMISTRY OF LIPIDS 29

• Monoenoic acid (one double bond) 9

Palmitoleic acid 9
Oleic acid
16 1 15 0-7
Newonic acid 1
18 0-9
• Dienoic acids (two double bonds) 1 9, 12
24 0-9
Linoleic acid
• Trienoic acid (three double bonds) 9, 12, 15
Linolenic acid 18 2 0-6
• Tetraenoic acid (four double bonds)
Arachidonic acid 18 3 0-3
• Pentaenoic acid (five double
bonds) 4 7, 10,13, 16, 19 0-6
20

Clupandonic acid 22 5 0-3

• Docosa hexaenoic acid (DHA)
Cewonic acid 22 6 0-3
Table 3.1: Some naturally occurring fatty acids
Common name Carbon atoms Double bonds Position of double bond Unsaturated fatty acid class

Saturated fatty acids

Unsaturated fatty acid

Some naturally occurring fatty acids are given in Table Fatty acids, in which the carbons are arranged linearly,
3.1. are subclassified into two classes:
i. Saturated fatty acids ii.
Classification of Fatty Acids Unsaturated fatty acids.
Fatty acids are classified into four major classes (Figure 3.1).
Saturated fatty acids
There is no double bond in the hydrocarbon chain of
I . Straight chain fatty acids
these fatty acids. Saturated fatty acids are subclassified
2. Branched chain fatty acids into two classes:
3. Substituted fatty acids a. Even carbon acids carry even number of carbons,
4. Cyclic fatty acids. e.g. palmitic acid and stearic acid.
Straight Chain Fatty Acids b. Odd carbon acids carry odd number of carbons, e.g.
propionic acid.
30 ESSENTIALS OF BIOCHEMISTRY

Unsaturated fatty acids 16 14 13 12 10 9 8

These contain double bonds in their hydrocarbon Cerebronic acid and oxynervonic acids of brain
chains. glycolipids
These are subclassified according to the number of Ricinoleic acid of castor oil.
double bonds present in the structure as follows:
a. Monoenoic or monounsaturated fatty acid Cyclic Fatty Acids
b. Polyenoic or polyunsaturated fatty acid. Fatty acids bearing cyclic groups are present in some

Figure 3.1: Classification of fatty acids

Monoenoic or monounsaturated fatty acids carry a bacteria and seed lipids, e.g. hydnocarpic acid
single double bond in the molecule, e.g. oleic acid. (Chaulmoogric acid) of chaulmoogra seed.
Polyenoic or polyunsaturated fatty acids contain two
or more double bonds; for example: Functions of Fatty Acids
Dienoic acids have two double bonds, e.g. Fatty acids have three major physiological functions.
linoleic acid present in soyabean, 1. They serve as building blocks of phospholipids and
sunflower, saffola and groundnut oil. glycolipids. These amphipathic molecules are
important components of biological membranes.
Trienoic acids have three double bonds, e.g.
2. Fatty acid derivatives serve as hormones, e.g.
Linolenic acid present in poppyseed oil, prostaglandins.
linseed oil. 3. Fatty acids serve as a major fuel for most cells.
Tetraenoic acid with four double bonds, e.g.
arachidonic acid present in groundnuts. Numbering of Fatty Acid Carbon Atoms (Figure
Branched Chain Fatty Acids 3.2)
These are less abundant than straight chain acids in Fatty acid carbon atoms are numbered starting at the
anirnals and plants, e.g. carboxyl terminus.
Isovaleric acid
Isobutyric acid.

Substituted Fatty Acids

In substituted fatty acids one or more hydrogen atoms
have been replaced by another group, e.g.
Lactic acid of blood
 CHEMISTRY OF LIPIDS 31

CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-
COOH
(D

Palmitic acid
Figure 3.2: Numbering of fatty acid carbon
7 6 5 4 3 2 1 Fatty acids, that are required for optimal health and
Carbon atoms 2 and 3 are often referred to as oc and cannot be synthesized by the body and should be
respectively. supplied in the diet are called essential fatty acids.
They are polyunsaturated fatty acids, namely
The methyl carbon atom at the distal end of the chain
linoleic acid and linolenic acid. Arachidonic acid can be
is called omega (o) carbon.
synthesized from linoleic acid. Therefore, in deficiency
Representation of Double Bonds of Fatty Acids of linoleic acid, arachidonic acid also becomes essential
fatty acids.
Two systems are used to designate the position of
Humans lack the enzymes to introduce double bonds
double bond: at carbon atoms beyond C9 in the fatty acid chain.
C-system Hence,
' o- or n-system. humans cannot synthesize linoleic acid and linolenic
C-System acid having double bonds beyond C9. And thus, linoleic
In C-system (i.e. Cl being the carboxyl carbon) the and linolenic are the essential fatty acids.

position of double bond is represented by the symbol A Functions of Essential Fatty Acids (EFA)
(delta), followed by a superscript number. Synthesis of Eicosanoids
For example, oleic acid is a C18 fatty acid with
one double bond between carbon number 9 and 10
is Linoleic acid and linolenic acid supplied by the diet
represented as C: 18: 1: A9 (Figure 3.3). are the precursors for the synthesis of a variety of other
unsaturated fatty acids. Arachidonic acid, a fatty acid
o- or n-System derived from linoleic acid is an essential precursor of
In this system, or 'n' refers to the carbon of their terminal eicosanoids, which include:
methyl group in a fatty acid. In Œsystem or n-system, Prostaglandins
the oleic acid is denoted as C: 18:1:o-9 (Figure 3.3) to
Thromboxanes Prostacyclin
indicate that:
' 0-9 represents the double bond position which is found Leukotrienes.
between 9th and 10th carbon atoms, the first carbon
atom being that of the terrni_nal methyl group. This Maintenance of Structural Integrity
method is widely used by nutritionists.
Naturally occurring unsaturated fatty acids belong to EFAs are required for membrane structure and function.
0-9, 0-6 and 0-3 series. For example, These fatty acids are important constituents of
0-9 : Oleic acid phospholipids in cell membrane and help to maintain
the structural integrity of the membrane.
0-6 : Linoleic acid
Arachidonic acid Development of Retina and Brain
0-3 : Linolenic acid Docosahexaenoic acid (DHA: 0-3), which is
synthesized from linolenic acid is parficularly needed
ESSENTIAL FATTY ACIDS for development of the brain and retina during the
neonatal period.

Antiatherogenic Effect
32 ESSENTIALS OF BIOCHEMISTRY

Essenfial fatty acids increase esterificafion and cholesterol level. Thus, essential fatty acids help to
excretion of cholesterol, thereby lowering the serum prevent the atherosclerosis.
18 17 16 15 14 13
12 10 9 8 1
CH 3 — CH=CH— (CH2)7— COOH
9

Oleic acid (C: 18 : 1 : A) in C-system

OR
(D

1 2 3 4 5 6 7 8 9 7 18
CH3—CH2— CH2— CH2— CH2— CH2— CH2— CH2— CH=CH— (CH2h— COOH
Oleic acid (C: 18 : 1 : 0-9) in (D-system

Figure 3.3: Representation of double bonds of unsaturated fatty acid

Essential Fatty Acid Deficiency include vitamin E (tocopherol) and ß-carotene (provitamin A), which are lipid
soluble and vitamin C, which is water
Deficiency of EFAs is characterized by scaly skin, Rancidity
eczema (in children), loss of hair and poor wound
The unpleasant odor and taste, developed by natural fats
healing.
upon aging, is referred to as "rancidity". Rancidity may
Impaired lipid transport and fatty liver may occur
be due to hydrolysis or oxidation of fat.
due to deficiency of EFAs.
EFAs deficiency decreases efficiency of biological Rancidity due to hydrolysis: Naturally occurring fats,
oxidation. particularly those from animal sources, are
contarninated with enzyme lipase. The action of
lipase brings about partial hydrolysis of glycerides
REACTIONS OF LIPIDS of fat.
Rancidity may also be caused by various oxidative
Saponification processes. For example, oxidation at the double bonds of
unsaturated fatty acids of glycerides may form peroxides,
Hydrolysis of a fat by alkali is called saponification.
which then decompose to form aldehydes of unpleasant
The products are glycerol and the alkali salts of the fatty
odor and taste, this process is increased by exposure to light
acids, which are called soaps (Figure 3.4). Acid or heat.
hydrolysis of a fat yields the free fatty acids and Many natural vegetable fats and oils may contain
glycerol.
soluble.

o Hydrogenation
Hydrogenation of unsaturated fats in the presence of a
CH2—OH O catalyst (nickel) is known as "hardening". It is
Cid—OH commercially valuable as a method of converting these
liquid fats, usually of plant origin into solid fats as
margarines, vegetable ghee, etc.
CH1 2—01-1

Peroxidation
Triacylglycerol Glycerol Na-salt of fatty acid (a soap)
Peroxidation (auto-oxidation) of lipids exposed to
Figure 3.4: Saponification of fat oxygen is responsible not only for deterioration of foods
(rancidity) but also for damage to tissues in vivo, where
it may be a cause of cancer. Lipid peroxidation is a
chain reaction generating free radicals that initiate
 CHEMISTRY OF LIPIDS 33

further peroxidation. To confrol and reduce Butter = 26

peroxidation, humans make use of antioxidants. Coconut oil = 7.
Naturally occurring anfioxidants antioxidants like It is less than one for other edible oils. The
vitarnin E which prevent onset of rancidity. Therefore, adrnixture of certain fats may be used to prepare
vegetable fats can be preserved for a longer time than synthetic butter which may simulate butter in most of
animal fats. the constants except RM value and hence, can be
detected.
CHARACTERIZATION OF FAT (TESTS
FOR PURITY OF FAT)
Fats are characterized and their purity assayed by the
NEUTRAL FAT
following tests: TRIACYLGLYCEROLS OR
TRIACYLGLYCERIDES OR
Saponification Number
It is defined as, number of mgs of KOH required to These are esters of fatty acids with glycerol.
saponify one gm of fat. It is inversely proportional to Triacylglycerol consists of three fatty acids, which are
the molecular weight of fat. This value is high in fats esterified through their carboxyl groups, resulting in a
containing a short chain fatty acids. For example, the loss of negafive charge and formafion of neutral fat.
saponification nurnber of: (Figure 3.5).
Butter = 220 Triacylglycerols containing the same kind of fatty
acid in all three positions are called simple
Coconut oil = 260
triacylglycerols. Mixed triacylglycerols contain
Iodine Number two or more different fatty acids. The fatty acid on
carbon 1 is usually saturated. That on carbon 2 is
The number of gms of iodine required to saturate 100 usually unsaturated and that on carbon 3 can be
gms of a given fat is known as iodine nurnber. Since either of the two. The stereospecific numbering (sn)
iodine is taken up by the double bonds, a high iodine of the glycerol carbon atom is shown in Figure 3.5.
number indicates a high degree of unsaturation of the
As the polar hydroxyl groups of glycerol and polar
fatty acids in fat, e.g.
carboxyl groups of the fatty acids are bound in ester
Butter fat = 27
Coconut oil = 8 O
Linseed oil = 200.
Iodine number is important in the idenfificafion of
1 CH2—01-1
the fat or oil as well as is used for idenffication of
HOOC— RI
adulteration of oils.
Acid Number 2 CH —OH
Number of mg of KOH required to neutralize the free HOOC—2 + 31- 120 3
fatty acids present in one gm of fat is known as acid CH2—OH
number. The acid number indicates the degree of HOOC—R3
rancidity of the given fat. Acid number is directly
proportional to the rancidity. The edibility of a fat is
inversely proportional to the acid nurnber. Glycerol Fatty acids Triacylglycerol
Refined oil should not contain free fatty acids. The Figure 3.5: Glycerol and triacylglycerol
presence of free fatty acids in any oil indicates that it is linkages, triacylglycerols are nonpolar, hydrophobic
not pure. and neutral (in charges) molecules, essentially
insoluble in water.
Reichert Meissl Number The presence of the unsaturated fatty acid(s) in
The number of ml of 0.1 N alkali, required to neutralize triacylglycerol decreases the melting temperature of
the volatile fatty acids distilled from 5 gm of fat, e.g. the lipid and remains in liquid form (oil).
the Reichert Meissl value for:
34 ESSENTIALS OF BIOCHEMISTRY

Vegetable oils such as corn and olive oil are

composed largely of triacylglycerols with
unsaturated fatty acids and thus are liquids at room
temperature.
Triacylglycerols containing only saturated fatty
acids, such as beef fat, are white greasy solids at
room temperature.
Nonpolar,
Triacylglycerols are highly concentrated storage
hydrophobic region
form of metabolic energy.
Head
Polar, hydrophilic region
cPHOSPHOLIPIDS

Nonpolar tail
These are made up of fatty acid, glycerol or other
Polar head
alcohol, phosphoric acid and nitrogenous base.
Phospholipids are the major lipid constituents of cell Figure 3.6: Diagrammatic representation of amphipathic
membranes. phospholipid
Like fatty acids, phospholipids are amphipathic in
nature, i.e. each has a hydrophilic or polar head Classification of Phospholipids
There are two classes of phospholipids (Figure 3.7):
O
1 1. Glycerophospholipids or phosphoglycerides,
that contain glycerol as the alcohol.
Fatty acid 2. Sphingophospholipids that contain sphingosine
as the alcohol.
Glycerophospholipids or Phosphoglycerides
Glycerol Phospholipids derived from glycerol are called
(phosphate group) and a long hydrophobic tail
phosphoglycerides or glycerophospholipids.
(containing two fatty acid chains) (Figure 3.6).
Figure 3.7: Phospholipid

Glycerophospholipid or phosphoglyceride, e.g. Sphingophospholipid, e.g.

• Phosphatidylcholine (lecithin) • Sphingomyelins

• Phosphatidylethanolamine (Cephalin)

• Phosphatidylserine

• Phosphatidylinositol

• Plasmalogens
• Lysophospholipids

• Cardiolipin
 CHEMISTRY OF LIPIDS 35

Classification of phospholipids

is necessary for normal lung function. It reduces surface tension in the alveoli, thereby prevents alveolar collapse
(adherence of the inner surfaces of the lungs).
Acute Pulmonary Respiratory Distress Syndrome (RDS)
RIDS in infants is associated with insufficient surfactant dipalmitoyl phosphatidylcholine production.
Phosphoric acid ' The lungs of immature infants do not have enough type Il epithelial cells to synthesize
sufficient amounts Phosphatidic acid of dipalmitoyl phosphatidylcholine (DPPC).
' In its absence, the lungs tend to collapse and this
Figure 3.8: Structure of glycerol and phosphatidic acid
condition is known as respiratory distress syndrome.
In glycerophospholipid, the hydroxyl groups at Cl and Phosphatidylethanolanine (Cephalin)
C2 of glycerol are esterified with two fatty acids. The They differ from lecithin in having nitrogenous base
ethanolarnine in place of choline (Figure 3.9).
C3 hydroxyl group of the glycerol is esterified to Thromboplastin (coagulation factor Ill), which is
phosphoric acid and resulting compound called, needed to initiate the clotting process, is composed
phosphatidic acid (Figure 3.8). mainly of cephalins.
Phosphatidic acid is a key intermediate in the
biosynthesis of other glycerophospholipids.
In glycerophospholipid, phosphate group of phosphatidic
acid becomes esterified with the hydroxyl group of one of the
several niftogen base or other groups. Different types of
glycerophospholipids are discussed below.
Phosphatidylcholine (lecithin)
These are glycerophospholipids containing choline
(Figure 3.9). These are most abundant
phospholipids of the cell membrane having both
structural and metabolic functions.
Dipalmitoyl lecithin is an important
phosphatidylcholine found in lungs, secreted by pulmonary
type Il epithelial cell. It acts as a lung surfactant and
Phosphatidylserine
It contains the amino acid serine rather than
ethanolarnine and is found in most tissues (Figure
3.9).
Phosphatidy/inosito/
• In
phosphatidylinosit
ol, inositol is
present as the
stereoisomer
myoinositol
(Figure 3.9).
36 ESSENTIALS OF BIOCHEMISTRY

Phosphatidylinositol is a second messenger for the

action of hormones like oxytocine and vasopressin.
Plasmalogens
Plasmalogens are generally similar to other

Phosphatidylethanolamine

phospholipids but the fatty acid at Cl of glycerol is

linked through an ether, rather than an ester bond
(Figure 3.9).
• 0— CH2
Myoinositol
0— CH2 O—CH R2—c—O—CH CH
O CH2—O—
 CHEMISTRY OF LIPIDS 37

OH
Phosphatidylcholine (Lecithin)
Phosphatidylinositol

O Ether linkage

0— CH2
O—CH O
O CH Ethanolamine o-
Plasmalogen

oO
Lysophospholipid (lysolecithin) o

O CHEO—C— RI
O CH —
o Glycerol
CHž-O—P— O-CHrCHOH-CH2-O-P-O—Cl-12
o- o
Phosphatidylserine
Cardiolipin or diphosphatidyl glycerol

Figure 3.9: Structure of different phospholipids

There are three major classes of from glycerophospholipid. The most
plasmalogens: common of these are
i. lysophosphatidylcholine
Phosphatidylcholines (lysolecithin) (Figure 3.9) and
ii. lysophosphatidylethanolarnine.
Phosphatidylethanolam
Cardiolipin (Diphosphatidylglycerol)
ines iii.
Phosphatidylserines. Cardiolipin is composed of two
These are found in myelin and in molecules of phosphatidic acid
cardiac muscle. connected by a molecule of
glycerol.
Plasmalogen is a platelet
activating factor (PAF) and Two molecules of phosphatidic acid
involved in platelet aggregation esterified through their phosphate
and degranulation. groups with a molecule of glycerol
are called cardiolipin (Figure
Lysophospholipids
3.9).
Lysophospholipids are produced when
one of the two fatty acid is removed
38 ESSENTIALS OF BIOCHEMISTRY

Cardiolipin is a major lipid of Phospholipids are of importance in insulating the newe

mitochondrial membrane and is impulse (like the plastic or rubber covering around an
necessary for optimum function of electric wire) from the surrounding structures, e.g.
the electron transport process. sphingomyelins act as eletrical insulators in the myelin
sheath around nerve fibers. Phospholipids are
This is only human glycerophospholipid that possess important constituents of lipoproteins.
antigenic properties.
Phospholipids act as a lipotropic factor. Lipotropic
factor is the component that prevents fatty liver,
Sphingophospholipids i.e. accumulation of fat in the liver.
Phospholipids derived from alcohol sphingosine instead of These are good emulsifying agents that help in
glycerol are called sphingophospholipids, e.g. sphingomyelin
intestinal absorption of lipids.
Sphingomyelin Thromboplastin (coagulation factor Ill), which is
Sphingomyelin is the only phospholipid in needed to initiate the clotting process, is composed
mernbranes that is not derived from glycerol. mainly of cephalins.
Instead, the alcohol in sphingomyelin is Phospholipid (lecithin) acts as lung surfactant,
sphingosine, an amino alcohol. which prevents alveolar collapse.
In sphingomyelin, the amino group of the Lecithin represents a storage form of lipotropic
sphingosine is linked to a fatty acid to yield factor choline.
ceramide (sphingosinefatty acid complex). Phosphatidylinositol acts as a second messenger for
In addifion, the primary hydroxy group of
sphingosine is esterified with phosphorylcholine
the activity of certain hormones.
(Figure 3.10). Sphingomyelin is one of the
principal structural lipids of membranes of nerve In mitochondria, cardiolipin is necessary for
tissue. optimum fuctions of the electron transport process.
Plasmalogens (platelet activating factor) involved
Ceramide (Fatty acid + sphingosine) in platelet aggregation and degranulation.

GLYCOLIPIDS (GLYCOSPHINGOLIPIDS
)
Glycolipids as their name implies, are sugar
containing lipids. Glycolipids consist of alcohol
Fatty acid
sphingosine.
CH2 The arnino group of sphingosine is esterified by a
fatty acid and one or more sugar units are attached
o to the hydroxyl group of sphingosine.
Glycolipids are widely distributed in every tissue of
the body, particularly in nervous tissue such as
brain.
Phosphorylcholine
(Phosphoric acid + Choline) Classification of Glycolipids
Four classes of glycolipids have been distinguished:
Figure 3.10: Structure of sphingomyelin
1. Cerebrosides
2. Sulfatides
Functions of Phospholipids
3. Globosides
Phospholipids are the major lipid constituents of cell
4. Gangliosides.
membranes.
They regulate permeability of membranes as well as Cerebrosides (Ceramide + Monosaccharides)
activation of some membrane bound enzymes. Cerebroside is the simplest glycolipid in which there is
 CHEMISTRY OF LIPIDS 39

only one sugar residue, either glucose or galactose Ganglioside contains oligosaccharides and one or
linked to ceramide and narned as glucocerebroside and more molecules of sialic acid, which is usually
galactocerebroside respectively. Nacetylneuraminic acid (NANA) attached to ceramide.
Galactocerebroside is found in nerve tissue Several types of gangliosides such as GMI, GM2,
membrane. whereas glucocerebroside is the GM3, etc. have been isoloted from brain and other
predominant glycolipid of extraneural (non-neural) tissues. The simplest ganglioside found in tissues is
tissues, where it acts as a precursor for the synthesis GM3. G represents Ganglioside, M represents mono
of more complex glycolipids, e.g. gangliosides. which indicate presence of one residue of NANA and
subscript number assigned on the basis of
Ceramide chromatographic migration of ganglioside.
Sphingosine - Fatty
Ceramide
acid
Sphingosine - Fatty acid

Glucose or Galactose
Glucose - Galactose - NANA
Cerebroside
Sulfatides (Ceramide + Monosaccharide + Sulfate) GM3 - Ganglioside
Sulfatides are cerebrosides in which the GMI is a more complex ganglioside derived from
monosaccharide contains a sulfate ester. GM3.
Ceramide Ceramide
Sphingosine - Fatty Sphingosine - Fatty acid
acid

Glucose - galactose - N - acetylgalactosamine - galactose

Monosaccharide - Sulfate

Sulfatide NANA

GMI _ Ganglioside
Globosides (Ceramide + Oligosaccharide)
Globosides contain two or more sugar molecules
attached to ceramide. Functions of Glycolipids
These glycolipids are important constituents of the Glycolipids are important constituents of the
RBC-membrane and are the deterrninants of the nervous tissue, such as brain and outer leaflet of all
cell membrane.
A,B,O blood group system They play a role in the regulation of cellular
interactions, growth and development.
Ceramide
Glycolipids serve as cell surface receptors for
Sphingosine - Fatty certain hormones and a number of drugs. They also
acid serve as receptors for cholera and tetanus toxins.
Glycolipids are antigenic and they have been
identified as a source of blood group antigens.
Oligosaccharide

Globoside CHOLESTEROL (ANIMAL STEROL)

Gangliosides: (Cerebroside + Oligosaccharides + N-
acetylneuraminic acid, NANA)
Cholesterol is the major sterol in anirnal tissues.
Gangliosides are complex glycolipids, derived from Sterols are a class of steroids containing hydroxyl
glucocerebroside.
40 ESSENTIALS OF BIOCHEMISTRY

group. It consists of steroid nucleus namely Cholesterol is amphipathic, with a polar head the
phenanthrene containing 19-carbon atoms (Figure hydroxyl group at C3 and a nonpolar, the steroid
3.11). It consists of methyl side chains at position nucleus and hydrocarbon side chain at C17.
CIO and C13 which are shown as single bonds. Most of the cholesterol in the body exists as a
Cholesterol, a 27-carbon compound, has an 8- cholesterol ester, with a fatty acid attached to
carbon side chain attached to the D ring at C17 and the hydroxyl group at Q.
a hydroxyl group attached to C3 of the A ring, with
one double Cholesterol is widely distributed in all the cells of
bond between carbon atoms 5 and 6 (Figure 3.12). the body but particularly in nervous tissue.
It occurs in animal fats but not in the plant fats.

Functions of Cholesterol
It is a major structural constituent of the cell
membranes and plasma lipoproteins. Cholesterol

Figure 3.11: The steroid nucleus, phenanthrene (ring A, B and C),

to which cyclopentane D ring is attached
serves as the precursor for a variety of biologically
important products, including:
1. Steroid hormones: Cholesterol is the precursor
of the five steroid hormones, e.g.
i. Progesterones ii. Glucocorticoids
iii. Mineralocorticoids iv.
22
21 CH3 Androgens (male sex hormones) vi.
26 Estrogen (female sex hormones).
4—Nonpolar tail 2. Bile acids: Bile acids, derived from cholesterol,
27 (hydrophobic act as a detergent in the intestine, emulsifying
group)
dietary fats to make them readily accessible to
digestive enzyme lipase.
OH 3. Vitamin D: It is derived from cholesterol and is
4 6 essential in calcium and phosphate metabolism.
18
LIPOPROTEINS
16

Lipoproteins are large water soluble complexes

15
formed by a combination of lipid and protein that
2
transport insoluble lipids through the blood between
different organs and tissues.
3
Lipoproteins consist of a lipid core containing
4 6 14 nonpolar triacylglycerol and cholesterol ester
15
14 surrounded by a single layer of amphipathic
phospholipids and free cholesterol molecules with
some proteins, (apoprotein) (Figure 3.13).
The protein components are referred to as an
Polar head (hydrophilic group) apoprotein or apolipoprotein. There are four major
types of apolipoproteins designated by letters A, B,
Figure 3.12: The structure of cholesterol
C and E with subgroups given in Rornan numerals
1, 11, 111, etc.
 CHEMISTRY OF LIPIDS 41

Peripheral apoprotein proporfional to triacylglycerol content. As the

Monolayer of amphipathic lipid density increases, the diarneter of the particle
(phospholipid and free decreases as shown in Figure 3.14.
cholesterol)
Phospholipid Chylomicrons containing about 1 percent
Free cholesterol protein and 99 percent triacylglycerol have the
Core of nonpolar lipids lowest density.

Variable Chylomicron VLDL LDL HDL

Diameter (nm) 70 to 1200 25 to 70 20 to 25 5 to 10
Density (g/ml) < 0.95 0.95 to 1 .006 1.019 to 1.063 1.063 to 1.210
Lipid-Protein ratio 99:1 90:10 80:20 50:50

Major lipids Triacylglycerol Triacylglycerol Cholesterol Phospholipids

Apolipoproteins B-48 B-lOO A, C and E
Lipid components (0/0)
Triacylglycerol 86 55 6 5
Cholesterol 5 20 50 20
(free and ester)

Phospholipid 7 18 22 25
Very large Eicosanoids are synthesized from arachidonic acid. A polyunsaturated fatty acid containing
20-carbon atoms from which they take their
general name (Greek: eikosi means twenty).

Prostaglandins
(cholesterol ester and triacylglycerol) While HDL containing 50 percent of protein and 50
percent of lipid have the highest density.
Triacylglycerol is the predominant lipid in
Figure 3.13: Structure of lipoprotein where,
TG: triacylglycerol, CE: cholesterol ester chylomicrons and VLDL. Cholesterol is the
predominant lipid in LDL, whereas
phospholipid is the predominant lipid in HDL.
Percentage of three major lipid classes, i.e.
triacylgly cerol, cholesterol and phospholipids
Classes of Lipoproteins present in lipoproteins are shown in Table 3.2.
Lipoproteins have been categorized into four major Large
Smallest
classes according to their physical and chemical

O
properties (Table 3.2). These are .
1. Chylomicrons HDL
2. Very low density lipoproteins (VLDL)
Density increases
3. Low density lipoprotein (LDL)
4. High density lipoprotein (HDL).
% Protein increases
These lipoprotein complexes contain different
proportions of lipids and proteins (Table 3.2). The
density of these lipoproteins is inversely Diameter decreases
42 ESSENTIALS OF BIOCHEMISTRY

Figure 3.14: Diagrammatic representation of lipoprotein with now known to be present in almost all tissues.
increasing densities
Chemically, the prostaglandins are derivatives of the
Site of Synthesis and Functions of Lipoproteins
The site of synthesis of the four main lipoproteins and hypothetical parent compound prostanoic acid, having
their functions are summarized in Table 3.3. cyclopentane (5 carbon) ring and two aliphatic side
chains RI and R2 (Figure 3.15).
Prostanoic acid does not occur naturally but is

EICOSANOIDS regarded as the parent compound of the

prostaglandins and thromboxanes for the purpose of
Prostaglandins and the related compounds
classification and carbon numbering.
thromboxanes and leukotriens, are collectively
In addition to cyclopentane ring, each of the
known as Prostaglandins are a group of 20-carbon
biologically active prostaglandin has a hydroxyl group
compounds derived from arachidonic acid (Figure
at carbon 15, a double bond between carbons 13 and
3.15).
They derive their name from the tissue in which they 14, and various substituents on the ring.
were first recognized (the prostate gland) but they are
eicosanoids.

main lipoproteins of
Site of synthesis Function

Chylomicrons Intestine Transport of dietary lipids from intestine to peripheral tissues

VLDL Liver Transport of triacylglycerol from liver to peripheral tissues
LDL Plasma VLDL Transport of cholesterol from liver to peripheral tissues
HDL Liver and intestine Transport of free cholesterol from peripheral tissues to the liver
(Reverse cholesterol transport)
Table 3.3: The four and their site synthesis and function
 CHEMISTRY OF LIPIDS 43

CooH the action of many hormones, the prostaglandins affect a wide range
of cellular and tissue functions. Some of these are:
Arachidonic acid Smooth muscle contraction and relaxation: For example, in pregnancy
1 PGF2Πare produced in COOH response to oxytocin and act to promote
uterine contraction. Because of this effect, they have been 0 used to terminate
unwanted pregnancies. PGE2 are involved in relaxation of bronchial smooth
11 13 15 17 19
muscle.
Prostanoic acid
Inflammatory response: PGs are involved in
O inflammatory response causing pain, edema, Cool-I swelling and prolonged erythema
(abnormal flushing of skin) by increasing capillary permeability.
aggregation and are thus, involved in the blood CooH clotting.

OH OH Platelet aggregation: Prostaglandins have an

PGE2 effect on platelet aggregation. PGE2 promote
Regulation of Blood pressure: PGE2 decrease blood pressure.
It can lower systemic arterial OHI pressure through their vasodilator effect.
Body temperature: Prostaglandins elevate body
O
temperature producing fever and cause inflam-
Cool-I
mation, resulting in pain.
Gastric secretion: PGE2 suppress gasfric secretion.
LTA4in Na and water retention by PGs are involved kidney tubules.
Figure 3.15: The structure of arachidonic acid, prostanoic acid, Prostaglandins and other eicosanoids have hormone
common prostaglandin (PGE2), thromboxane (TXA2) and like actions.
leukotrienes (LTA4)
Prostaglandins in many tissues act by regulating the
synthesis of cyclic AMP (cAMP). As cAMP
Classification of prostaglandins mediates
By convention, prostaglandins are abbreviated as Thromboxanes
PG. They are classified into groups designated by
a capital letter (A, B, C, D, E, F, G, H and 1) Thromboxanes were first isolated from blood platelets,
depending on the substituents on the cyclopentane thrombocytes—hence the name. They have six
ring. membered oxane ring (Figure 3.15) that includes an
These are subclassified by a subscript number 1, 2, oxygen atom.
or 3 corresponding to the number of double bonds in
the side chains but not in the cyclopentane ring.
Nomenclature of thromboxanes
Sixteen naturally occurring prostaglandins have
been described but only seven are found commonly Thromboxanes are abbreviated as TX.
throughout the body. These are PGEI, PGE2, Different capital letters are used to designate
PGFIŒ, different substituents of the ring (like
PGF2Œ, PGG2, PGH2, PG12. prostaglandins).
Prostaglandins are not stored, instead the precursor A subscript, if present, denotes the number of
C20 arochidonic acids are stored in tissues. unsaturated bonds (double bonds), e.g. the most
Functions of prostaglandins
 ESSENTIALS OF BIOCHEMISTRY

common thromboxane TXA2 having two charged hydrophilic heads are exposed on the surface
double bonds. facing the aqueous medium (Figure 3.16).

Functions of thromboxanes is produced by Lipid Bilayer

platelets, promotes platelets aggregation. Platelet Phospholipids also readily and spontaneously form a
aggregation initiates thrombus formation at sites of very thin bilayer separating two aqueous compartments.
vascular injury. In these structures, the hydrocarbon tails of the
causes contractions of the smooth muscles of phospholipid molecules extend inward from the two
the arterial wall and therefore, raises blood pressure. surfaces to form a
Leukotrienes (LT) continuous inner
hydrocarbon
Leukotrienes were so narned because they were initially core and the hydrophilic
described in leucocytes and are characterized by a heads face outwards
conjugated triene system but no such ring structure that extending into the
is found in prostaglandins and thromboxanes. aqueous phase
Nomenclature of leukotrienes (Figure 3.16).
Nonpolar
All leukotrienes are abbreviated as LT.
phase
These are grouped into five classes (A to E) based
Aqueous
on the type of substituents attached to the parent
Aqueous phasephase
compound.
The LTs found in humans have a subscript four to
denote that they contain four double bonds (Figure
3.15).
Functions of leukotrienes Liposome
The LTs facilitate chemotaxis, inflammation and
allergic reactions.
LTC4, LTD4 induce contraction of muscle of the lung Hydrophilic
and constrict pulmonary airways. Overproduction of region
LT causes asthmatic attacks.
Aqueous
LTD4 has been identified as the slow reacting phase
substance of anaphylaxis (SRS-A) which causes
smooth muscle contraction.
LTB4 attracts neutrophils and eosinophils to sites of Hydrophobic region
inflarnmation. Micelle

MICELLES, LIPID BILAYER AND LIPOSOMES

Aqueous phase
Micelles
The polar lipid like phospholipid is amphipathic in
nature. It has a hydrophilic or polar head (phosphate
Hydrophobic
Aqueous phase
group attached to choline, ethanolamine, inositol, etc.)
and a long hydrophobic tail containing two fatty acid A phospholipid bilayer
chains (Figure 3.16). In aqueous systems the polar
phospholipid spontaneously disperse to form micelles, Figure 3.16: Formation of micelle, a phospholipid
in which the hydrocarbon tails of the phospholipid are bilayer and liposome
hidden from the aqueous environment and electrically
 CHEMISTRY OF LIPIDS 45

Liposome (Artificially Formed Phospholipid Cholesterol, a sterol is a precursor of many steroids

Vesicles) and is also an important constituent of plasma
membranes of the cell.
Liposomes are artificially formed aqueous vesicles Lipoproteins are macromolecular complexes that
enclosed by a lipid bilayer. fransport insoluble lipids in the blood. The proteins
In the laboratory, liposomes (lipid bilayer) are of the lipoprotein are referred to as apoprotein or
formed by suspending phospholipid in an aqueous apolipoprotein
medium and then sonicating, i.e. agitating by high
Prostaglandins, thromboxanes and leukotrienes are
frequency sound waves to give a dispersed closed
derived from PUFA arachidonic acid. Liposomes
vesicles. Vesicles formed by these methods are
are artificially formed phospholipid vesicles.
nearly spherical in shape (Figure 3.16) and have a
diameter of about 5 nm. Detergents are amphipathic molecules, and are not
natural membrane constituents.
Liposomes can be used to study membrane
permeability or to deliver drugs to cells.

DETERGENTS

Detergents are amphipathic molecules and are not

natural membrane constituents. In aqueous
solutions, they form micelles, with the hydrophilic
42

regions on the outside, interacting with the water,

and the hydrophobic regions inside.
The bile acids and bile salts are powerful naturally
occurring detergents which emulsify fats in the
digestive tract; they can also be used to solubilize
membrane proteins.
Lysophospholipids also have detergent like action.

SUMMARY
Lipids are water insoluble components of cells.
Some lipids serve as structural component of
membrane and others as storage form of fuel.
Triacylglycerols contain three fatty acid molecules
esterified to the three hydroxyl groups of the
glycerol and are storage fats.
The polar lipids (phospholipids, glycolipids and
cholesterol), which have polar heads and
nonpolar tails, are amphipathic and major
components of membranes.
Sphingolipids, i.e. sphingomyelins, cerebrosides
and gangliosides are also membrane components
and contain sphingosine but no glycerol.

Cerebrosides and gangliosides are glycolipids which

contain various sugar components.