LECTURE NOTE

ON
LIPID CHEMISTRY
FOR
MBBS STUDENTS (200 LEVEL)
BY
ALHASSAN A. SIDDAN
BIOCHEMISTRY DEPARTMENT
GOMBE STATE UNIVERSITY
DECEMBER, 2021
 LIPIDS
• Lipids are bio-molecules that are:
 Hydrophobic in nature because of the high amount of
Hydrocarbons in their structure,
 Relatively insoluble in water but readily soluble in non-
polar solvents such as Chloroform, Benzene and Ether,
acetone, etc.
 Most lipids are chemically esters of fatty acids and
alcohols.
 In addition, some lipids contain phosphoric acid,
nitrogenous bases, protein, sulphate and sugar residues.
 Lipids are widely present in both animals and plants and
are fundamental structural component of cell.
 Triglycerides, phospholipids proteolipids, glycolipids,
cholesterol, eicosanoids, Fat-soluble Vitamins (Vitamins A,
D, E and K), etc are common examples of lipids
 CLASSIFICATION OF LIPIDS
Lipids are classified into 3 major
classes:
Simple lipids
Compound lipid
Derived lipids
Other classification of lipids is called
Miscellaneous lipids
 Simple lipids:

• Simple lipids: Esters that fatty acids

form with various alcohols. They have
been subdivided in to two groups:
i. Fats and oils,
ii. Waxes
• Fats and oils are esters of Fatty Acids
with glycerol(e.g TGs; simple and mixed)
• Waxes are esters of fatty acids with
alcohols other than glycerol)
 Complex or compound lipids
• Are esters of fatty acids and alcohols with
some additional groups.
• Complex lipids are subdivided in to:
• Phospholipids: composed of fatty acids,
glycerol or sphingosine, Pi and nitrogenous
bases. They have been subdivided in to:
 Glycerophospholipids (composed of fatty
acids, glycerol (alcohol, Pi and nitrogeneous
bases e.g lecithin, cephalin, etc.)
 Sphingophospholipids (composed of fatty
acids, sphingosine (alcohol), Pi and
nitrogenous bases
 Glycolipids/Glycosphingolipids
• Glycolipids composed of fatty acids,
sphingosine and sugar residues.
• They have been divided in to:
• Cerebrosides and
• Gangliosides
 Cerebrosides (simple glycolipids) composed of
fatty acids, sphingosine and glucose/galactose
residue, e.g cerebron, nervon, etc.
 Gangliosides (complex glycolipids): composed
of fatty acids, sphingosine, hexose residues
and sialic acid e.g GM1, GM2, etc
 Proteolipids

• Proteolipids are composed of lipids and

protein, e.g VLDL, LDL, HDL, etc

Sulpholipids
• Sulpholipids are sulphated glycolipids.
 Derived Lipids
• These are derived from simple and complex lipids.
e.g ketone bodies, eicosanoids, steroids, alcohols,
fatty acids, etc.
• Ketone bodies: acetoacetate, acetone and 3-
hydroxybutyrate( derived from fatty acids)
• Eicosanoids: Prostaglandins and Prostacyclins
(derived from arachidonic acid)
• Steroids: Compounds containing “steroids
nucleus”, e.g cholesterol, bile acids, vitamin D,
steroid hormones, etc.
• Alcohols: Glycerol and sphingosine
• Fatty acids: Saturated and Unsaturated fatty
acids e.g palmitic acid, oleic acid, linolenic acid,
etc.
 Miscellaneous Lipids
Example, vitamin K and E, carotenoids
 Simple Lipids (Fats and Oil)
• Fats and oils are fatty acid esters of glycerol, e.g Triacylglycerols
(also known as glycerides), diacylglycerols and monoacylglycerols.
• Triglycerides (TGs) are composed of one glycerol moeity and three
molecules of fatty acids, and are most abundant lipids in nature.
• Fats and oils are widely distributed as TGs in both plants (in seeds)
and animals (in adipose tissues)
• Fats and oils contain both saturated and unsaturated fatty acids.
 Simple and mixed TGs
• The are two types of TGS: Simple and mixed TGs.
• Simple TGs are composed of Glycerol and three identical
fatty acids, whereas
• Mixed TGs contain glycerol and two or three different
fatty acids

Example of Simple TGs.

• Triolein (Tri-oleoyl-glycerol) contains three molecules of
Oleic acid residues esterified to a molecule of Glycerol,
• Tri-stearin (Tri-stearoyl-glycerol) contains three Stearic
acid residues esterified to a molecule of glycerol.
Examples of mixed TGs:
• 1-palmitoleoyl-2-linoleoyl-3-stearoyl-glycerol;
• 1,3-dipalmitoleoylstearoyl-glycerol.
 Waxes
 Waxes are esters of long chain fatty acids
with high molecular weight monohydroxy
aliphatic alcohols.
 In contrast to fats and oils, waxes are
composed of only one molecule of fatty
acid and one molecule of alcohol (other
than glycerol) e.g triacontanoyl palmitate,
major component of bee wax, etc
 Compound or Complex Lipids

• These are esters of fatty acids and

alcohols with some additional groups such
as phosphoric acid, nitrogenous bases,
protein, sulphate and sugar residues. The
compound lipids have been subdivided into
four major groups:
• Phospholipids
• Glycolipids
• Proteolipids and
• Sulfolipids.
 PHOSPHOLIPIDS:
• Phospoholipids are composed of fatty
acids, alcohol (either glycerol or
sphingosine), phosphoric acid and
nitrogenous base. Depending on the type
of alcohol present, phospholipids have
been further classified in two two
groups:
1. Glycerophospholipids (or
phosphoglycerides) containing glycerol as
an alcohol.
2. Sphingophospholipid (or sphingomyelins)
containing sphingosine as an alcohol.
 Glycerophospholipids
• These are the most common phospholipids. A
phosphoglyceride molecule consists of two molecules of
fatty acids, a glycerol molecule, a phosphoric acid residue
(P) and a nitrogeneous base.

• The phosphoglycerides are derived from phosphatidic acid

by addition of a nitrogenous base to the phosphatidic acid
molecule, and are named on the basis of the type of
nitrogenous base present, e.g phosphoglycerides containing
nitrogenous base choline and ethanolamine are called
phosphatidylcholine and phosphatidylethanolamine
respectively.

• The 3 chief nitrogenous bases present in

glycerophospholipids are choline, ethanolamine and serine.
 Phosphatidic acid
 This is the simplest phospholipid. it does not occur in good
concentration in the tissues. Basically, phosphatidic acid is an
intermediate in the synthesis of triacylglycerol and phospholipids.
The other glycerophospholipids containing different nitrogenous
bases or other groups may be regarded as the derivatives of
phosphatidic acid.
 Phosphatidylcholine (Lecithin)
• Phosphatidylcholine is the choline derivative of phosphatidic acid and
is commonly known as lecithin. On hydrolysis, a lecithin molecule yields
two fatty acids, a glycerol, a phosphoric acid residue and a
nitrogenous base choline.
• Various combination of saturated and unsaturated fatty acids are
present in lecithin.
• Lecithin are widely distributed in animal tissues (liver, brain, nerves
etc).
 Phosphatidylethanolamine (Cephalin)
• Phosphatidylethanolamine is the ethanolamine derivative of
phosphatidic acid and is commonly known as cephalin. Thus,
lecithin and cephalin differ with regard to the base.
• On hydrolysis, a cephalin molecule yields two fatty acids, a
glycerol, a phosphoric acid residue and a nitrogenous base
ethanolamine.
• Cephalin are distributed in animal tissues and also in plant.
 Phosphatidylinositol
• The steroisomer myo-inositol is attached to phosphatidic
acid to give phosphatidyl inositol: This is an important
component of cell membranes. The action of certain
hormones (e.g. oxytocin, vasopressin) is mediated through
Pl.
 Phosphatidylserine
• The phosphatidylserine is the serine (amino acid)
derivative of phosphatidic acid.
• It found more in brain and nervous tissues. It represent
about 16% of the total phospholipids.
• Phosphatidylserine is essential for normal cognitive
function of human neurons. It is responsible for the
targeting and functioning of several intracellular
signaling proteins.
 Plasmalogens
Chemically, plasmalogen differ from glycerophospholipids at C-1 of
glycerol, where a fatty acid is replaced by a long-chain aliphatic
aldehyde.
• In plasmalogens, an ether linkage (in place of ester linkage) is
formed at c-1 of glycerol.
• On hydrolysis, a plasmalogen molecule yields a long-chain
aliphatic aldehyde, a fatty acid, a glycerol, a phosphoric acid
residue and a nitrogenous base.
• The N.B is usually ethanolamine; choline, serine or inositol may
replace ethanolamine.
• Plasmologens are predominantly present in heart muscles, and
constitute about 10% of the total phospholipids of brain and
muscles.
 Cardiolipin
• Cardiolipin is the major phospholipids of the
inner mitochondrial membrane, where it
constitute about 20% of the total lipids.
• The name ‘cardiolipin’ was given because it was
first of all isolated from cardiac muscles.
• It is a phosphatidyl-glycerol derivative of
phosphatidic acid; in place of N.B,
phosphatidyl-glycerol is present in cardiolipin
• On hydrolysis, a cardiolipin molecule yields
two molecules of phosphatidic acids and one
molecule of glycerol.
 Sphingophospholipids
• The sphingophospholipids ( also known as sphingomyelins) are
found in most membranes of animal cells but present in large
quantity in brain and nervous tissues. On the basis of the alcohol
present, the sphingophospholipids differ from
glycerophospholipids.
• In place of glycerol, the sphingomyelins contain an unsaturated
18 carbon amino-alcohol known as sphingosine.
• On hydrolysis, one molecule of sphingomyelin yields one molecule
of sphingosine, a fatty acid, a phosphoric acid residue and a
nitrogenous base (choline or ethanolamine)
 Glycolipids
• Glycolipids are sugar (e.g glucose, galactose,
sialic acid, etc,) containing lipids and are
widely distributed in almost all animal tissues
but predominantly in brain and nervous
tissues.
• These lipids are also known as
glycosphingolipids and are composed of fatty
acids, sphingosine and sugar.
• Unlike phospholipids, the glycosphingolipids do
not contain phosphoric acid residues.
• Glucolipids have been subdivided in to two
groups:
• (i) Cerebrosides
• (ii) Gangliosides
 Cerebrosides
• These are simple glycolipids. A cerebroside molecule is composed of
one molecule of high molecular weight fatty acid, a sphingosine and a
galactose or glucose residue.
• The cerebrosides containing glucose and galactose as sugar residue
are known as glucocerebroside (glucosylceramide) and
galactocerebrosides (galactosylceramide), respectively.
• Most of the cerebrosides are found in brain and peripheral nervous
tissues.
 Gangliosides
• Gangliosides are complex glycolipids containing sialic acid. These lipids
are composed of long chain fatty acids, sphingosine, hexose residues
and N-acetylneuraminic acid (NANA, also known as sialic acid).
• Gangliosides were first isolated from beef brain and are found in
large amount of grey matter of brain..
• The chemical structures of gangliosides are not well established.
• On hydrolysis, gangliosides yield a long chain fatty acid, a sphingosine,
hexose residues (glucose and/or galactose), N-acetylgalactosamine
and one or more sialic acid.
 Proteolipids
• Proteolipids (also known as lipoproteins) are
molecular complexes of lipids and proteins
(known as apoprotein).
• On the basis of their density, proteolipids are
of four major types:
 Chylomicrons
 Very Low Density Lipoprotein (VLDL)
 Low Density Lipoprotein (LDL)
 High Density Lipoprotein (HDL)
• The lipid components of lipoproteins are TGs,
cholesterol, cholesteryl ester and
phospholipids.
 Chylomicrons
• Chylomicrons: They are synthesized in the
intestine and transport exogenous (dietary)
triacylglycerol to various tissues. They
consist of highest (99%) quantity of lipid and
lowest (1%) concentration of protein. The
chylomicrons are the least in density and the
largest in size, among the lipoproteins.
 Very low density lipoproteins (VLDL):

• They are produced in liver and intestine

and are responsible for the transport of
endogenously synthesized
triacylglycerols.
• VLDL is composed of 95% lipids and 5%
protein
• The lipid component of VLDL is 15% PL
and 20% Ch.
 Low density lipoproteins (LDL):
• They are formed from VLDL in the blood
circulation. They transport cholesterol
from liver to other tissues.
• LDL is composed of 80% lipids and 20%
protein.
• The lipid component of LDL include 50% Ch,
22% PL and 8% TG.
 High density lipoproteins (HDL):

• They are mostly synthesized in liver.

HDL particles transport cholesterol
from peripheral tissues to liver (reverse
cholesterol transport).
• HDL has highest density among all
lipoprotein and composed of 60% lipids
and 40% proteins
 Sulfolipids
• This group includes sulfo-glycolipids containing
sulfated hexose residue, e.g galactocerebroside-
3-sulfate.
• Sulfolipids are found in brain, liver, kidney,
salivary glands, testicles etc.
• Sulfolipids are abundant in white matter of brain
and myelin sheath.
 Derived Lipids
• These are derived from simple and
complex/compound lipids.
• The derived lipids includes fatty acids,
Eicosanoids, steroids, alcohols (glycerol and
sphingosine), ketone bodies, etc.
 Fatty acids
• Fatty acids mainly occur as esters in various kinds
of lipids (triglycerides, phospholipids and
glycolipids).
• More than 90% of the fatty acids present in
blood exist as fatty acid esters contained in
plasma lipoproteins.
• Almost all natural lipids yield free fatty acids on
their hydrolysis.
• Chemically, fatty acids are monocarboxylic
organic acids with an aliphatic hydrocarbon chain
(alkyl chain) containing 4-36 carbon atoms.
• Most of the fatty acids present in natural lipids
have carbon atoms up to 24.
 Fatty acids…

• Fatty acids have been divided in three groups on

the basis of the length of hydrocarbon chain.
• Short chain fatty acids with less than or equal to
6 carbon atoms
• Medium chain fatty acids with 8-14 carbon atoms
and
• Long chain fatty acids with 16-24 carbon atoms.
 Types of fatty acids
• Fatty acids have been divided in two groups
on the basis of presence of double bond:
 Saturated fatty acids and
 Unsaturated fatty acids
• Both saturated and unsaturated fatty acids
occur in all natural lipids, but their proportion
varies in plant and animal fats
 Saturated fatty acids
• The Alkyl chain of saturated fatty acids contains
no double bond.
• The saturated fatty acids having carbon atoms ten
or less are liquid at room temperature and are
called ‘lower fatty acids. E.g butyric acid (4C),
caproic acid (6C), caprylic acid (8C), and capric acid
(10C).
• The saturated fatty acids having carbon atoms
more than ten are solid at room temperature and
are called ‘higher fatty acids’. E.g lauric acid (12C),
myristic acid (14C), palmitic acid (16C), stearic acid
(18C), arachidonic acid (20C), lignoceric acid (24C).
• The systematic name of a saturated fatty acid is
based on the hydrocarbon from which it is derived
and ends with a suffix –anoic. Eg butanoic acid
 Unsaturated fatty acids
• The Alkyl chain of unsaturated fatty acids contain one or more
double bonds.
• The systematic name of an usaturated fatty acid is based on
the hydrocarbon from which it is derived and ends with a
suffix –enoic, e.g palmitic acid.
• The unsaturated fatty acids have been further divided in two
major groups on the basis of the number of double bonds:
i. Monounsaturated fatty acids and
ii. Polyunsaturated fatty acids
• Monounsaturated fatty acids contain one double bond and is
present between C-9 and C-10. e.g Palmitoleic acid and oleic
acid.
• Polyunsaturated fatty acids (PUFA) contain two or more double
bonds (2-6).
• Linoleic acid, linolenic acid and arachidonic acid are the
examples of polyunsaturated fatty acids.
•
 Polyunsaturated fatty acids

 Polyunsaturated fatty acids are grouped into Three series or families

based on the Omega nomenclature. The groups are:
ω 9 or n-9 series:
 Fatty acids in which the first double bond is between C9 and C10
counting from the ω -carbon;
• Examples: Oleic acid and Gondoicacid

ω 6 or n-6 series:
 Fatty acids in which the first double bond is between C6 and C7
counting from the ω -carbon;
• Examples: Linoleic acid and Arachidonic acid

ω 3 or n-3 series:
 Fatty acids in which the first double bond is between C3 and C4
counting from the ω -carbon;
• Examples: α-Linolenic acid and Timnodonic acid
 Nomenclature of unsaturated fatty acid
• The systematic name of an unsaturated fatty acid
is based on the hydrocarbon chain from which it is
derived and ends with a suffix –enoic.
• The carbon numbering in a fatty acid chain start
from the carboxyl carbon (C-1)
• In fatty acid chain, carbon atom to which the –
COOH group is attached (i.e C-2) is called α-carbon,
C-3 is β-carbon and C-4 is γ-carbon.
• The carbon atom terminal methyl group (-CH3) is
called ω-carbon or n-carbon regardless of the chain
length.
• The position of a double bond can also be counted
from terminal –CH3 group, i.e, from ω-carbon or n-
carbon of fatty acid chain. For example, ω-6
indicates the presence of first double bond on C-6
counting from the ω-carbon of a fatty acid chain.
 cont’d
• The oleic acid, linoleic acid, linolenic acid and arachidonic acid
belong to three series of ω-fatty acids namely ω-3, ω-6 and ω-9
fatty acids.
• Abbreviations are used to show the total number of carbon
atoms, total number of double bonds and the position of double
bonds in unsaturated fatty acids, e.g, palmitic acid 16:1;9.

Examples:
 Oleic acid: ω 9, C18:1
– ω 9 means Oleic acid contains a double bond between C9 and
C10 counting from the ω -carbon atom (i.e., from the last
Carbon atom in the fatty acid molecule);
– C18:1, means 18C atoms, one double bond;
 Linoleic acid: ω 6, C18:2
– ω 6 means Linoleic acid contains a double bond between C6 and
C7 counting from the ω -carbon atom,
– C18:2, means 18C atoms, two double bonds, the first double
bond is between C6 and C7 counting from the ω -carbon;
– ω-C3 series fatty acids e.g linolenic acid
Omega Nomenclature
Schematic diagrams of Saturated and
Unsaturated Fatty Acids
 Essential fatty acids
 ESSENTIAL FATTY ACIDS are Unsaturated
fatty acids that cannot be biosynthesized in
tissues of some animals including humans, thus
they must be obtained in the diet. Examples:
• Linoleic acid (18:2;9,12) and
• α-Linolenic acid (18:3;9,12,15)
 Most of the essential fatty acids are members of
the ω 6 and ω 3 series;
 Some animals including humans can biosynthesize
Arachidonic acid from Linoleic acid obtained in
the diet;
 Thus, Linoleic acid is called True Essential Fatty
Acid;
 Eicosanoids
• Prostaglandins and related compounds like
prostacyclins, thromboxanes and leukotrienes
are collectively known as eicosanoids.
• Eicosanoids (Greek: Eikosi means Twenty) are
synthesized from arachidonic acid, a
polyunsaturated fatty acid with 20 carbon
atoms.
• For the synthesis of eicosanoids, arachidonic
acid is usually derived from the carbon-2 of
glycerol moiety of membrane-
glycerophospholipids by the action of enzyme
phospholipase A2.
• Arachidonic acid is also obtained from dietary
fats/oils.
 Eicosanoids…
• Eicosanoids are paracrine hormones;
eicosanoids serve as local hormones as they
act locally on tissues near the point of
their synthesis and need to be transported
in blood to act on distant tissues.
• Eicosanoids have been divide in two groups:
a. Prostanoids and
b. Leukotrienes and lipoxins
 STEROIDS
 A steroid is a biologically active organic compound with four rings
arranged in a specific molecular configuration. Steroids have two
principal biological functions: as important components of cell
membranes which alter membrane fluidity; and as signaling
molecules. Hundreds of steroids are found in plants, animals and
fungi.
 The steroid core structure is composed of seventeen carbon atoms,
bonded in four " fused" rings: three six-member cyclohexane rings
(rings A, B and C) and one five-member cyclopentane ring (the D
ring).
 Steroids…
• The steroids of biomedical importance are:
• Sterols (animal and plant sterols
• Vitamin D (vitamin D2 and D3)
• Bile acids and Bile salts
• Steroids hormones
• Plant glycosides
 Examples of steroids include:

 Testosterone, the principal male sex hormone

and an anabolic steroid
 Progesterone, a steroid hormone involved in
the female menstrual cycle, pregnancy.
 Types of Steroids
Corticosteroids:
 Corticosteroids are actually the most common type of steroid
currently in existence. They are produced above the kidneys
via the adrenal cortex and they include natural steroidal
hormones responsible for optimal health and function of the
body.
 Corticosteroids are divided into two classes:
Mineralocorticoids and Glucocorticoids.
Mineralocorticoids:
 Mineralocorticoids are a variant of corticosteroids which
function by helping to ensure everything internally remains as
it should. In particular, they help to ensure that sodium levels
within the body remain fully balanced.
Glucocorticoids:
 Glucocorticoids are also steroid hormones that play a vital
role in the active uptake of macronutrients within the human
body. Glucocorticoids also help to regulate a person’s
metabolism and influence how we process fats, proteins, and
carbohydrates.
 Sterols
 Sterols, also known as steroid alcohols, are a subgroup of the
steroids and an important class of organic molecules. They occur
naturally in plants, animals, and fungi, and can be also produced by
some bacteria (however likely with different functions). The most
familiar type of animal sterol is cholesterol, which is vital to cell
membrane structure, and functions as a precursor to fat-soluble
vitamins and steroid hormones.
 Sterols of plants are called phytosterols and sterols of animals are
called zoosterols.
 Vitamin D
• Vitamin D2 (ergocalciferol) and vitamin D3
(cholecalciferol) are steroids that are derived
from photolysis of B-ring of ergosterol
(provitamin D2) and 7-dehydrocholesterol
(provitamin D3) in presence of UV rays
respectively.
 BILE ACIDS
 Bile is a complex fluid containing water, electrolytes and
a battery of organic molecules including bile acids,
cholesterol, phospholipids and bilirubin that flows
through the biliary tract into the small intestine. There
are two fundamentally important functions of bile in all
species: Bile contains bile acids, which are critical for
digestion and absorption of fats and fat-soluble vitamins
in the small intestine.
 Many waste products, including bilirubin, are eliminated
from the body by secretion into bile and elimination in
feces.
 Types of Bile Acids
• Bile acids are conjugated with taurine or glycine in
the liver, and the sodium and potassium salts of these
conjugated bile acids are called bile salts. Primary
bile acids are those synthesized by the liver.
Secondary bile acids result from bacterial actions in
the colon.
 BILE SALTS
• Primary bile acids conjugate with glycine and
taurine, via amide linkage between the –COOH
group of bile acid and –NH2 group of glycine or
taurine, to yield glycocholic acid,
glycochenodeoxycholic acid, taurocholic acid and
taurochenodeoxycholic acid.
 PROSTAGLANDINS
 Prostaglandins (PG) contain a five-carbon ring originating
from the chain of arachidonic acid. Their name derives
from the prostate gland, the tissue from which they were
first isolated by Bengt Samuelsson and Sune Bergström.
Two groups of prostaglandins were originally defined: PGE,
for ether-soluble, and PGF, for phosphate ( fosfat in
Swedish) buffer–soluble. Each group contains numerous
subtypes, named PGE1, PGE2, and so forth.
 There are four principal bioactive prostaglandins
(taking place in living body):
 Prostaglandin (PG) E2 (PGE2),
 Prostacyclin (PGI2),
 Prostaglandin D2 (PGD2)
 and Prostaglandin F2α (PGF2α).
Prostaglandins