Chemistry of

Lipids
 Lipids
• Lipids constitute a heterogeneous group of compounds of
biochemical importance.
• Lipids may be defined as compounds which are relatively
insoluble in water, but freely soluble in nonpolar organic
solvents like benzene, chloroform, ether, hot alcohol,
acetone, etc.
• They are esters of fatty acids with alcohol esters and
are utilizable by the living organism
 Functions of Lipids
• 1. Storage form of energy (triglycerides)
• 2. Structural components of biomembranes (phospholipids and cholesterol)
• 3. Metabolic regulators (steroid hormones and prostaglandins)
• 4. Act as surfactants, detergents and emulsifying agents (amphipathic
lipids)
• 5. Act as electric insulators in neurons
• 6. Provide insulation against changes in external temperature
(subcutaneous fat)
• 7. Give shape and contour to the body
• 8. Protect internal organs by providing a cushioning effect (pads of fat)
• 9. Help in absorption of fat soluble vitamins (A, D, E and K)
• 10. Improve taste and palatability of food.
 CLASSIFICATION OF LIPIDS
1 . Simple lipids : Esters of fatty acids with alcohols. These are
mainly of two types
(a) Fats and oils (triacylglycerols:) These are esters of fatty
acids with glycerol. The difference between fat and oil is only
physical. Thus, oil is a liquid while fat is a solid at room
temperature.
(b) Waxes: Esters of fatty acids (usually longchain) with alcohols
other than glycerol. These alcohols may be aliphatic or alicyclic.
Cetyl alcohol is most commonly found in waxes
2. Complex (or compound) lipids:
These are esters of fatty acids with alcohols containing
additional groups such as phosphate, nitrogenous base,
carbohydrate, protein etc. They are further divided as
follows
(a)Phospho lipids: They contain phosphoric acid and
frequently a nitrogenous base. This is in addition to
alcohol and fatty acids.
(i) Glycerophospholipid: These phospholipids contain
glycerol as the alcohol e.g., lecithin, cephalin.
(ii) Sphingophospholipids: Sphingosine is the alcohol in this
group of phospholipids e.g., sphingomyelin
(b) Glycolipids:
• These lipids contain a fatty acid, carbohydrates and
nitrogenous base. The alcohol is sphingosine hence they
are also called as glycosphingolipids. Glycerol and
phosphate are absent e.g., cerebrosides, gangliosides.
(c) Lipoproteins:
• Macromolecular complexes of lipids with proteins.
(d) Other complex lipids:
• Sulfolipids, aminolipids and lipopolysaccharides are
among the other complex lipids.
3. Derived lipids:
• These are the derivatives obtained on the hydrolysis of
group 1 and group 2 lipids which possess the
characteristics of lipids. These include fatty acids, glycerol
and other alcohols, mono- and diacylglycerols lipid (fat)
soluble vitamins, steroid hormones, hydrocarbons and
ketone bodies.
4. Miscellaneous lipids:
• These include a large number of compounds possessing
the characteristics of lipids e.g., carotenoids, squalene,
hydrocarbons such as pentacosane (in bees wax), terpenes
etc.
 FATTY ACIDS
• Fatty acids are carboxylic acids with hydrocarbon chains
(–CH2–CH2–CH2) and represented by a chemical formula
R-COOH, where R stands for hydrocarbon chain.
• It is the most common component of lipids in the body.
They are generally found in ester linkage in different
classes of lipids. In the human body free fatty acids are
formed only during metabolism.
• The fatty acids are amphipathic in nature, i.e. each has
hydrophilic (COOH) and hydrophobic (hydrocarbon chain)
groups in the structure.
 Classification of Fatty Acids
• Fatty acids are classified into four major classes
1. Straight chain fatty acids
2. Branched chain fatty acids
3. Substituted fatty acids
4. Cyclic fatty acids.
1. Straight Chain Fatty Acids
• Fatty acids, in which the carbons are arranged linearly, are
subclassified into two classes:
i. Saturated fatty acids
ii. Unsaturated fatty acids.
i. Saturated fatty acids
• There is no double bond in the hydrocarbon chain of these fatty
acids. Saturated fatty acids are subclassified into two classes:
a. Even carbon acids carry even number of carbons, e.g. palmitic
acid and stearic acid.
b. Odd carbon acids carry odd number of carbons, e.g. propionic
acid.
ii. Unsaturated fatty acids
• These contain double bonds in their hydrocarbon chains.
subclassified according to the number of double bonds present in
the structure as follows:
a. Monoenoic or monounsaturated fatty acid
b. Polyenoic or polyunsaturated fatty acid.
• Monoenoic or monounsaturated fatty acids carry a single
double bond in the molecule, e.g. oleic acid.
• Polyenoic or polyunsaturated fatty acids contain two or
more double bonds; for example:
– Dienoic acids have two double bonds, e.g. linoleic acid
present in soyabean, sunflower, saffola and groundnut oil.
– Trienoic acids have three double bonds, e.g. Linolenic
acid present in poppyseed oil, linseed oil.
– Tetraenoic acid with four double bonds, e.g. arachidonic
acid present in groundnuts.
Polyunsaturated fatty acids (PUFA)
Branched Chain Fatty Acids
• These are less abundant than straight chain acids in animals and plants,
e.g.
• 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
• Cerebronic acid and oxynervonic acids of brain glycolipids
• Ricinoleic acid of castor oil.
Cyclic Fatty Acids
• Fatty acids bearing cyclic groups are present in some bacteria and seed
lipids, e.g. hydnocarpic acid (Chaulmoogric acid) of chaulmoogra seed.
 Numbering of Fatty Acid Carbon Atoms
• Fatty acid carbon atoms are numbered starting at the
carboxyl terminus.
• Carbon atoms 2 and 3 are often referred to as α and β
respectively.
• The methyl carbon atom at the distal end of the chain is
called omega (ω) carbon.
Representation of Double Bonds of Fatty Acids
• Two systems are used to designate the position of double bond:
• C-system
• ω- or n-system.
C-System
• In C-system (i.e. C1 being the carboxyl carbon) the position of
double bond is represented by the symbol Δ (delta), followed by a
superscript number. For example, oleic acid is a C18 fatty acid with
one double bond between carbon number 9 and 10 is represented
as C: 18:1: Δ9
ω– or n-System
• In this system, ‘ω’ or ‘n’ refers to the carbon of their terminal
methyl group in a fatty acid. In ω-system or n-system, the oleic acid
is denoted as C: 18:1:ω-9
ESSENTIAL FATTY ACIDS
• Fatty acids, that are required for optimal health and
cannot be synthesized by the body and should be supplied
in the diet are called essential fatty acids.
• They are polyunsaturated fatty acids, namely linoleic acid
and linolenic acid. Arachidonic acid can be synthesized
from linoleic acid. Therefore, in deficiency of linoleic acid,
arachidonic acid also becomes essential fatty acids.
• Humans lack the enzymes to introduce double bonds at
carbon atoms beyond C9 in the fatty acid chain. Hence,
humans cannot synthesize linoleic acid and linolenic acid
having double bonds beyond C9. And thus, linoleic and
linolenic are the essential fatty acids.
Functions of Essential Fatty Acids (EFA)
• Synthesis of Eicosanoids
• Linoleic acid and linolenic acid supplied by the diet are
the precursors for the synthesis of a variety of other
unsaturated fatty acids. Arachidonic acid, a fatty acid
derived from linoleic acid is an essential precursor of
eicosanoids, which include:
• • Prostaglandins
• • Thromboxanes
• • Prostacyclin
• • Leukotrienes.
Maintenance of Structural Integrity
• EFAs are required for membrane structure and function.
These fatty acids are important constituents of phospholipids
in cell membrane and help to maintain the structural integrity
of the membrane.
Development of Retina and Brain
• Docosahexaenoic acid (DHA: ω-3), which is synthesized from
linolenic acid is particularly needed for development of the
brain and retina during the neonatal period.
Antiatherogenic Effect
• Essential fatty acids increase esterification and excretion of
cholesterol, thereby lowering the serum cholesterol level.
Thus, essential fatty acids help to prevent the atherosclerosis.
Representation of double bonds of unsaturated fatty acid
 Essential Fatty Acid Deficiency
• Deficiency of EFAs is characterized by scaly skin,
eczema (in children), loss of hair and poor wound
healing.
• Impaired lipid transport and fatty liver may occur
due to deficiency of EFAs.
• EFAs deficiency decreases efficiency of biological
oxidation.
 REACTIONS OF LIPIDS/FATTY ACIDS
Saponification
• Hydrolysis of a fat by alkali is called saponification. The
products are glycerol and the alkali salts of the fatty acids,
which are called soaps. Acid hydrolysis of a fat yields the
free fatty acids and glycerol.
Hydrogenation
• Hydrogenation of unsaturated fats in the
presence of a catalyst (nickel) is known as
“hardening”. It is commercially valuable
as a method of converting these liquid fats,
usually of plant origin into solid fats as
margarines, vegetable ghee, etc.
Halogenation
• When treated with halogens under mild
conditions, the unsaturated fatty acids can
take up two halogen atoms, at each double
bond to form the halogenated derivative of
the fatty acid. For example,
Oleic acid + I2 → Di-iodo oleic acid
• The number of halogen atoms taken up will
depend on the number of double bonds and
is an index of the degree of unsaturation.
Ester Formation
• Both saturated and unsaturated fatty acids
form esters with alcohols, especially with
glycerol. Fatty acids can form mono-, di- or
tri- esters with alcohol groups of glycerol.
Triglycerides or triacyl glycerols are also
known as neutral fat
Rancidity
• The unpleasant odor and taste, developed by natural fats
upon aging, is referred to as “rancidity”. Rancidity may
be due to hydrolysis or oxidation of fat.
• Rancidity due to hydrolysis: Naturally occurring fats,
particularly those from animal sources, are contaminated
with enzyme lipase. The action of lipase brings about
partial hydrolysis of glycerides of fat.
• Rancidity may also be caused by various oxidative
processes. For example, oxidation at the double bonds of
unsaturated fatty acids of glycerides may form peroxides,
which then decompose to form aldehydes of unpleasant
odor and taste, this process is increased by exposure to
light or heat.
• Many natural vegetable fats and oils may contain
Peroxidation
• Peroxidation (auto-oxidation) of lipids
exposed to 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 further peroxidation. To control and
reduce peroxidation, humans make use of
antioxidants.
CHARACTERIZATION OF FAT (TESTS FOR PURITY OF
FAT)
• Fats are characterized and their purity assayed by the
following tests:
Saponification Number
• It is defined as, number of mgs of KOH required to saponify
one gm of fat. It is inversely proportional to the molecular
weight of fat.
• This value is high in fats containing a short chain fatty acids.
For example, the saponification number of:
• Butter = 220
• Coconut oil = 260
Iodine Number
• The number of gms of iodine required to saturate 100
gms of a given fat is known as iodine number. Since
iodine is taken up by the double bonds, a high iodine
number indicates a high degree of unsaturation of the
fatty acids in fat, e.g.
• Butter fat = 27
• Coconut oil = 8
• Linseed oil = 200.
• Iodine number is important in the identification of the
fat or oil as well as is used for identification of
adulteration of oils.
Acid Number
• Number of mg of KOH required to neutralize the free
fatty acids present in one gm of fat is known as acid
number.
• The acid number indicates the degree of rancidity of
the given fat. Acid number is directly proportional to
the rancidity.
• The edibility of a fat is inversely proportional to the
acid number.
• Refined oil should not contain free fatty acids. The
presence of free fatty acids in any oil indicates that it
is not pure.
 TRIACYLGLYCEROLS OR
TRIACYLGLYCERIDES OR NEUTRAL FAT
• These are esters of fatty acids with glycerol.
Triacylglycerol consists of three fatty acids,
which are esterified through their carboxyl
groups, resulting in a loss of negative
charge and formation of neutral fat.
• •Triacylglycerols containing the same kind
of fatty acid in all three positions are called
simple triacylglycerols.
• Mixed triacylglycerols contain two or more
different fatty acids. The fatty acid on carbon 1 is
usually saturated. That on carbon 2 is usually
unsaturated and that on carbon 3 can be either of
the two.
• As the polar hydroxyl groups of glycerol and polar
carboxyl groups of the fatty acids are bound in ester
linkages, triacylglycerols are nonpolar, hydrophobic and
neutral (in charges) molecules, essentially insoluble in
water.
• The presence of the unsaturated fatty acid(s) in
triacylglycerol decreases the melting temperature of the
lipid and remains in liquid form (oil).
• 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.
• Triacylglycerols are highly concentrated
storage form of metabolic energy.
 PHOSPHOLIPIDS
• These are made up of fatty acid, glycerol or
other alcohol, phosphoric acid and
nitrogenous base.
• Phospholipids are the major lipid constituents of
cell membranes.
• Like fatty acids, phospholipids are
amphipathic in nature, i.e. each has a
hydrophilic or polar head (phosphate group)
and a long hydrophobic tail (containing two
fatty acid chains)
Classification of Phospholipids
There are two classes of phospholipids
1. Glycerophospholipids or
phosphoglycerides, that contain glycerol as
the alcohol.
2. Sphingophospholipids that contain
sphingosine as the alcohol.
 GLYCEROPHOSPHOLIPIDS OR
PHOSPHOGLYCERIDES
• Phospholipids derived from glycerol are
called phosphoglycerides or
glycerophospholipids.
• In glycerophospholipid, the hydroxyl groups at C1
and C2 of glycerol are esterified with two fatty
acids. The C3 hydroxyl group of the glycerol is
esterified to phosphoric acid and resulting
compound called, phosphatidic acid
 PHOSPHATIDYLCHOLINE (LECITHIN)
• These are glycerophospholipids containing choline.
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 II epithelial cell.
• It acts as a lung surfactant and 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).
 PHOSPHATIDYLETHANOLANINE
(CEPHALIN)
• They differ from lecithin in having nitrogenous
base ethanolamine in place of choline
• Thromboplastin (coagulation factor III),
which is needed to initiate the clotting process,
is composed mainly of cephalins.
PHOSPHATIDYLSERINE
• It contains the amino acid serine rather than
ethanolamine and is found in most tissues
 PHOSPHATIDYLINOSITOL
• In phosphatidylinositol, inositol is present as the
stereoisomer myoinositol.
• Phosphatidylinositol is a second messenger for
the action of hormones like oxytocine and
vasopressin.
PLASMALOGENS
• Plasmalogens are generally similar to other
phospholipids but the fatty acid at C1 of glycerol
is linked through an ether, rather than an ester
bond
• There are three major classes of
plasmalogens:
i. Phosphatidylcholines
ii. Phosphatidylethanolamines
iii. Phosphatidylserines.
• These are found in cardiac muscle.
• Plasmalogen is a platelet activating factor
(PAF) and involved in platelet aggregation
and degranulation.
 Lysophospholipids
• Lysophospholipids are produced when one
of the two fatty acid is removed from
glycerophospholipid.
• The most common of these are
lysophosphatidylcholine (lysolecithin) an
lysophosphatidylethanolamine.
 CARDIOLIPIN
(DIPHOSPHATIDYLGLYCEROL)
• Two molecules of phosphatidic acid
esterified through their phosphate groups
with a molecule of glycerol are called
cardiolipin
• Cardiolipin is a major lipid of mitochondrial
membrane and is necessary for optimum
function of the electron transport process.
 SPHINGOPHOSPHOLIPIDS
• Phospholipids derived from alcohol sphingosine instead of
glycerol are called sphingophospholipids, e.g. sphingomyelin.
Sphingomyelin
• Sphingomyelin is the only phospholipid in membranes that is
not derived from glycerol. Instead, the alcohol in sphingomyelin
is sphingosine, an amino alcohol.
• In sphingomyelin, the amino group of the sphingosine is linked
to a fatty acid to yield ceramide (sphingosinefatty acid
complex).
• In addition, the primary hydroxy group of sphingosine is
esterified with phosphorylcholine
• Sphingomyelin is one of the principal structural lipids of
membranes of nerve tissue.
 Functions of Phospholipids
• Phospholipids are the major lipid constituents of cell
membranes.
• They regulate permeability of membranes as well as
activation of some membrane bound enzymes.
• Phospholipids are of importance in insulating the nerve
impulse (like the plastic or rubber covering around an electric
wire) from the surrounding structures, e.g. sphingomyelins act
as electrical insulators in the myelin sheath around nerve
fibers.
• Phospholipids are important constituents of lipoproteins.
• Phospholipids act as a lipotropic factor. Lipotropic factor is
the component that prevents fatty liver, i.e. accumulation of
fat in the liver.
• These are good emulsifying agents that help in intestinal
absorption of lipids.
• Thromboplastin (coagulation factor III), which is needed to
initiate the clotting process, is composed mainly of cephalins.
• Phospholipid (lecithin) acts as lung surfactant, which
prevents alveolar collapse.
• Lecithin represents a storage form of lipotropic factor choline.
• Phosphatidylinositol acts as a second messenger for the
activity of certain hormones.
• In mitochondria, cardiolipin is necessary for optimum fuctions
of the electron transport process.
• Plasmalogens (platelet activating factor) involved in platelet
aggregation and degranulation.
 CHOLESTEROL (ANIMAL STEROL)
• Cholesterol is the major sterol in animal tissues. Sterols
are a class of steroids containing hydroxyl group.
• It is the most important animal steroid from which other
steroid compounds are formed.
• Cholesterol is widely distributed in animal tissues. It is
absent in prokaryotes.
• In plants, cholesterol is absent, but other plant sterols
are present.
• In bacteria and plants, compounds similar to steroids
exist, known as hopanoids.
 Structure of Cholesterol
1. All steroids have cyclopentano perhydro phenanthrene ring
system. It is a fused ring system made up of 3 cyclohexane rings
designated as A, B and C and a cyclopentane ring D.
2. Total 27 carbon atoms.
3. One hydroxyl group at third position which is characteristic
of all sterols. The OH group is betaoriented, projecting above the
plane of ring.
4. Double bond between carbon atoms 5 and 6.
5. An eight carbon side chain, beta-oriented, attached to 17th
carbon.
6. Cholesterol is amphipathic, with a polar head the hydroxyl
group at C3 and a nonpolar, the steroid nucleus and hydrocarbon
side chain at C17.
Structure of cholesterol
 Functions of Cholesterol
1. Cell membranes: Cholesterol is a component of membranes and has
a modulating effect on the fluid state of the membrane.
2. Bile acids: Bile acids, derived from cholesterol, act as a detergent in
the intestine, emulsifying dietary fats to make them readily accessible to
digestive enzyme lipase.
3. Vitamin D: It is derived from cholesterol and is essential in calcium
and phosphate metabolism.
4. Steroid hormones: Cholesterol is the precursor of the five steroid
hormones, e.g.
• i. Progesterones
• ii. Glucocorticoids
• iii. Mineralocorticoids
• iv. Androgens (male sex hormones)
• vi. Estrogen (female sex hormones).
5. Esterification: The OH group of cholesterol is esterified
to fatty acids to form cholesterol esters. This esterification
occurs in the body by transfer of a PUFA moiety by lecithin
cholesterol acyl transferase.
6. Nerve conduction: Cholesterol has an insulating effect
on nerve fibers.
 LIPOPROTEINS
• Lipoproteins are large water soluble complexes formed by
a combination of lipid and protein that transport insoluble
lipids through the blood between different organs and
tissues.
• Lipoproteins consist of a lipid core containing nonpolar
triacylglycerol and cholesterol ester surrounded by a
single layer of amphipathic phospholipids and free
cholesterol molecules with some proteins,
• The protein components are referred to as an
apoprotein or apolipoprotein.
Structure of lipoprotein where, TG: triacylglycerol, CE: cholesterol ester
 Classes of Lipoproteins
• Lipoproteins have been categorized into four major
classes according to their physical and chemical
properties . These are :
• 1. Chylomicrons
• 2. Very low density lipoproteins (VLDL)
• 3. Low density lipoprotein (LDL)
• 4. High density lipoprotein (HDL)
• These lipoprotein complexes contain different proportions of
lipids and proteins.
• The density of these lipoproteins is inversely proportional to
triacylglycerol content. As the density increases, the diameter of
the particle decreases,
• Chylomicrons containing about 1 percent protein and
99 percent triacylglycerol have the lowest density.
• While HDL containing 50 percent of protein and 50
percent of lipid have the highest density.
• Triacylglycerol is the predominant lipid in
chylomicrons and VLDL. Cholesterol is the
predominant lipid in LDL, whereas phospholipid is the
predominant lipid in HDL.
LDL and Clinical Applications
• LDL concentration in blood has positive correlation with
incidence of cardiovascular diseases.
• LDL infiltrates through arterial walls, and is taken
up by macrophages or scavenger cells. This is the
starting event of atherosclerosis leading to
myocardial infarction.
• Since LDL-cholesterol is thus deposited in tissues,
the LDL (low density lipoprotein) variety is called
“bad cholesterol” and LDL as “Lethally
Dangerous Lipoprotein”
Clinical Significance of HDL
• The level of HDL in serum is inversely related to the
incidence of myocardial infarction. As it is
“antiatherogenic” or “protective” in nature, HDL is
known as “good cholesterol” in common parlance. It is
convenient to remember that "H" in HDL stands for
"Healthy". HDL level below 35 mg/dl increases the risk,
while level above 60 mg/dl protects the person from
coronary artery diseases.
Micelles
• The polar lipid like phospholipid is amphipathic in nature.
It has a hydrophilic or polar head (phosphate group
attached to choline, ethanolamine, inositol, etc.) and a
long hydrophobic tail containing two fatty acid chains.
• In aqueous systems the polar phospholipid spontaneously
disperse to form micelles, in which the hydrocarbon tails
of the phospholipid are hidden from the aqueous
environment and electrically charged hydrophilic heads
are exposed on the surface facing the aqueous medium
Liposome (Artificially Formed Phospholipid Vesicles)
• Liposomes are artificially formed aqueous vesicles enclosed by a
lipid bilayer.
• In the laboratory, liposomes (lipid bilayer) are formed by
suspending phospholipid in an aqueous medium and then
sonicating, i.e. agitating by high frequency sound waves to give
a dispersed closed vesicles.
• Vesicles formed by these methods are nearly spherical in shape
and have a diameter of about 5 nm.
• Drugs, proteins, enzymes, genes, etc. may be encapsulated by
the liposomes which could act as carriers for these substances
to target organs.
• Liposome-entrapped drugs exhibit superior pharmacological
properties than those observed with conventional formulations.