CHEMISTRY OF LIPIDS

Dr. Abdulrahaman A. Momin

Associate Professor
Department of Biochemistry
Dr. Rajendra Gode Medical College,
Amravati
 SPECIFIC LEARNING OBJECTIVES (SLO’S)

CBME Competency No. 4.1

At the end of lectures, Phase-I MBBS students shall be able to…

• Describe biomedical importance, definition and classification of

lipids with suitable examples.
• Classify fatty acids and explain essential fatty acids with their
functions.
• Describe triglycerides with its function.
• Classify phospholipids and describe their functions.
• Describe the chemistry, functions and importance of cholesterol.
• Describe the structure, composition, functions and separation of
lipoproteins.
• Describe the amphipathic lipids and their applications.
• Correlate the Basic science of lipid chemistry with clinical context.
 DEFINITION

Lipids are They are relatively

heterogeneous group of insoluble in water and
organic compounds soluble in non-polar
related either actually or solvents such as ether,
potentially to fatty chloroform and
acids. benzene.
 GENERAL FUNCTIONS OF LIPIDS

1. Serve as an efficient source of energy.

2. 1 gm fat (Triacyl Glycerol -TAG) gives 9 Kcal of energy.
3. When present in subcutaneous tissue and around certain vital
organs, act as thermal and mechanical insulator. (TAG)
4. Act as electrical insulator allowing rapid propagation of nerve
impulse along myelinated nerves. (Cholesterol)
5. Structural components of biomembranes. (Phospholipids and
Cholesterol).
6. Act as surfactants, detergents & emulsifying agents.
(Phospholipids, Bile Salts)
7. Compounds synthesized from lipid are metabolic regulators.
(Steroid hormones & Prostaglandins).
 BIOMEDICAL IMPORTANCE
1. Excess deposition of TAG in adipose tissue leads to
obesity which is the risk factor for various diseases like
Diabetes mellitus, hypertension, cancer etc.
2. Excess deposition of TAG in liver leads to fatty liver.
3. Excess deposition of cholesterol and cholesterol esters
in arterial walls leads to atherosclerosis which is a risk
factor for coronary artery diseases, stroke etc.
4. The deranged metabolic processes during uncontrolled
diabetes mellitus and prolonged starvation leads to
excess breakdown of TAG leading to more oxidation of
fatty acids. This will result in ketosis (excess production
of ketone bodies that leads to decreased pH).
 CLASSIFICATION OF LIPIDS

Simple Complex Derived

E.g.: Fat (TAG) E.g: fatty acids,
Waxes, Glycerol, Steroids,
Oils 1) Phospholipids Cholesterol

G Glycerophospholipids
Sphingophospholipids
L Fatty acid - Phosphatidylcholine,
- Phosphatidylethanolamine, -sphingomyelin
Y
C - Phosphatidylserine,
Fatty acid - Phosphatidylinositol
E
R 2) Glycolipids
O e.g - Cerebrosides,
Fatty acid gangliosides
L
3) Other complex lipids
E.g.: Sulfolipids (sulfated cerebrosides), lipoproteins
FATTY ACIDS
• Derived lipid
• Definition:
These are linear carboxylic acids with
hydrocarbon chain (of 2 to 36 carbons)
and a terminal methyl group.
• General formula: CH3-(CH2)n-COOH
• Dietary sources of Fatty acids:
– Vegetable oils, nuts, fish are the
richest sources.
Classification of Fatty Acids

According to Number of Carbon Atoms

According to Saturation

Nutritional classification

Omega classification
Classification of Fatty Acids
According to Number of Carbon Atoms

Even Chain:

• Short chain(<10 ‘C’):

Acetic Acid C2 and Butyric acid C4
• Long chain (>10 ‘C’):
Palmitic acid C16 and Stearic Acid C18

Odd Chain:

• e.g.,: Propionic Acid C3

Classification of Fatty Acids
According to Saturation
Saturated (no double bond):
• e.g.,: Palmitic acid (C16), Stearic acid (C18)

Unsaturated (double bond present)

• Monounsaturated (MUFA): Single double bond
E.g.,: Oleic acid ( C18 : 1)
• Polyunsaturated Fatty Acids (PUFA): More than 1
double bond
E.g.,: Linoleic acid (C18: 2),
Linolenic acid (C18: 3),
Arachidonic acid (C20: 4)
Classification of Fatty Acids
Nutritional classification
Essential fatty acids/PUFAs
• Definition: They cannot be synthesized in the body,
hence must be supplemented in the diet.
• E.g.,: Linoleic acid, Linolenic acid, Arachidonic acid
• Sources: Sunflower, rice bran, soyabean
• Humans lack enzymes to introduce double bonds at
carbon beyond C9 in the fatty acid chain.
Non-essential fatty acids:
• Definition: Fatty acids which can be synthesized by the
body.
• E.g.,: Palmitic acid, Stearic acid.
Classification of Fatty Acids

Omega classification

Omega 3 fatty acids (ω3):

• E.g.,: Linolenic acid (3 Double bonds)

Eicosapentaenoic acid (EPA),
DHA (docosahexaenoic acid)
• Source: flax seed oil, fish oils are a rich source

Omega 6 fatty acids (ω6):

• E.g.,: Linoleic acid: vegetable oils are a rich source,

➢ Naturally occurring foods are rich in ω6 fatty acids
as compared to ω3, thus there is always a dietary
deficiency of ω3 and it must be consciously
supplemented in the diet.
➢ Optimal dietary ratio of ω6 to ω3 fatty acids
should be between 1:1 to 1:4 to decrease the risk of
cardiovascular diseases.
 FUNCTIONS OF ESSENTIAL FATTY
ACIDS AND OMEGA 3 FATTY ACIDS (ω3)

1. Arachidonic acid is the precursor for synthesis of

prostaglandins.
2. As a component of phospholipids, they maintain the
structural integrity & fluidity of cell membrane.
3. They act as lipotropic factors, thus prevent
formation of fatty liver.
4. Vital for development of nerve tissue, thus used in
treatment of Alzheimer’s disease, depression,
autism and brain development in infants.
5. Have anti-inflammatory role, decreased LDL, thus dietary
inclusion helps in prevention of atherosclerosis and
coronary artery diseases (CAD).

6. Anti-atherogenic effect: Cholesterol esters of PUFA’s are

easily metabolized, thus help to decrease serum cholesterol.

7. Higher concentration in reproductive tissue: role in

fertility.

Deficiency: Toad skin (Phrynoderma),

Scaly skin with eruptions

 CIS-TRANS ISOMERISM
• Describe the positions of the two hydrogen atoms located next
to the carbon atoms where the double bond exists.

• Fluidity of membrane is due to presence of cis fatty acids in

phospholipids.
 TRANS FATTY ACIDS
• During Hydrogenation, Cis → Trans
Trans F.As. are present in dairy products,
hydrogenated edible oils, fried and fast-food
preparations (they increase the shelf life of fried food).
• Trans F.As. are injurious to health causing
cardiovascular diseases.
• They increase the LDL levels leading to increased
deposition of cholesterol in the arterial walls leading to
atherosclerosis.
SIMPLE LIPIDS
 TRIACYLGLYCEROL (TAG)
• Triacylglycerols are the esters of fatty acid with
glycerol.
• Present in vegetable oils, dairy products, animal fat.
• Non-polar lipid.
• Stored in adipocytes.
• Rich Source of energy 9 Kcal/G
Simple: R1:R2:R3 are same.
Mixed: R1, R2 and R3 are different.
 PROPERTIES OF TRIACYLGLYCEROL

1. Hydrolysis: Important step in lipid digestion.

2. Rancidity:

3. Lipid peroxidation: Oxidation of lipids in living.

cell. to form peroxides and free radicals like O2 ,
OH which can damage various tissues.
Antioxidants: Vitamin E, C
Polar bear Pacific golden plover
Waxes:
• They are esters of higher fatty acids (having chain
of 60-100 carbon atoms) with high molecular
weight alcohol e.g., Cetyl Alcohol.
• They are used as base for preparation of cosmetics,
ointments, candles, polishes & lubricants.
Complex/
Compound
Lipids
 DEFINITION:
These are complex lipids
Phospholipids containing phosphoric acid and
nitrogen base in addition to
glycerol and fatty acids.
GLYCEROPHOSPHOLIPIDS
Ester linked Phospholipids

Ether Linked phospholipids:

Plasmalogens, Platelet Activating Factors (PAF)
Functions of
Phospholipids
 • Found in all cellular and subcellular
Phosphatidylcholine: organelle membranes.
(Lecithin) • Due to their amphipathic nature
maintain permeability and transport
across the membrane.
 Role as Lung Surfactant
• Dipalmitoyl lecithin derived
from phosphotidylcholine
acts as a lung surfactant.
• It prevents adherence and
collapse of alveoli by
reducing the surface tension
of alveolar fluid.
• Fetal lung development starts after 28 weeks of
gestation.
• Therefore, in prematurely born infants the risk of RDSN
(Respiratory Distress Syndrome of Newborns) is more.
• Assessment of fetal lung maturity is done by checking
Lecithin/Sphingomyelin (L/S) ratio in amniotic fluid:
• L/S of 2:1 indicates lung maturity.
• Low levels of lecithin leads to RDSN.
Treatment of
RDS of
newborn
Phosphatidyl serine & Phosphatidyl
ethanolamine (Cephalin)

-Helps in blood coagulation.

 Solubilizer of cholesterol in bile
• Cholesterol is surrounded by phosphatidylcholine to form bile
salt micelle.
• Bile salt (80 %) + phosphatidylcholine (15%) + cholesterol
(5%)
• Cholesterol is insoluble in aqueous medium like bile, through
which it is excreted out.
• Through the micelles, cholesterol is transported without
precipitation in bile
• If phospholipid concentration is decreased, cholesterol maybe
supersaturated or precipitated in bile as crystals.
• These crystals may grow to form Gall Stones.
 Phosphatidyl inositol
• Present in biomembranes.
• It plays a vital role in hormone action by acting as
second messenger.
Plasmalogens – Brain, cardiac and skeletal
muscles are rich in plasmalogens.
Platelet activating factor:
It causes platelets to aggregate & activate
thrombotic & inflammatory events.
Phospholipids are important for synthesis and
transport of lipoproteins.
Cardiolipin:
• Major lipid of mitochondrial membranes.
• Only phospholipid having antigenic property.
• also act as lipotropic factors, thus prevent formation of fatty
liver
• Detection of anticardiolipin and antiphospholipid antibodies
have a diagnostic role in autoimmune disorders.
Sphingomyelin:
• Found in large concentrations in brain and nerve tissue.
• Present in myelin sheath that insulates and protects nerve
fibre.
AMPHIPATHIC LIPIDS
 LIPOSOMES
• Liposomes are spherical vesicles varying in size from very
small (0.025 μ) to large (2.5 μ) consisting of one or more
phospholipid bilayers. This lipid bilayer enclose to form
liposomes.
• Prepared by sonication of mixtures of phospholipids and
cholesterol.
• Drugs, proteins, enzymes, genes may be encapsulated by the
liposomes which act as carriers for these substances to the
target organs.
• Important applications: Cancer chemotherapy, Antimicrobial
therapy, Gene therapy, Vaccines and Diagnostic imaging.
Advantages:
• Targeted delivery of drugs
• Overcome problem of gastric irritation
 GLYCOLIPIDS
• Include cerebrosides and gangliosides.
• Occurrence:
– Particularly nervous tissue.
– Cell membrane (cell surface cholesterol)
Cerebroside
Ganglioside:
- Concentrated in ganglion cells particularly nerve endings.

Sulfatide (Sulfo-lipid):
- Concentrated in brain especially white matter.

- High concentration in myelin

 Disorders of Sphingolipids
(Sphingomyelin, cerebrosides, gangliosides)
1. Niemann Pick Disease: Rare autosomal genetic defect in
lysosomal enzyme sphingomyelinase. Sphingomyelin
accumulates in brain ,spleen and liver. Evident in infants ,causes
early mental retardation and early death.

2. Gaucher’s Disease: lysosomal enzyme Beta glucosidase defect.

3. Tay Sach’s Disease: lysosomal enzyme hexosaminidase A defect.

4. Gullain Barre Syndrome: Autoimmune disorder in which our

body makes antibodies against own gangliosides. The resulting
inflammation damages peripheral nervous system leading to
paralysis.
DERIVED LIPIDS:
STEROIDS
 Derived Lipids: Steroids
• Steroids are highly important biological compounds
derived from cholesterol.
• Include adrenal cortical hormones, male and female
sex hormones, Vitamin D, bile acids and cardiac
glycosides like digitalis.

• All of them contain a CPP

ring
• (cyclopentano perhydro
phenanthrene ring).
CHOLESTEROL
 CHOLESTEROL
• Faint yellow crystalline solid
• Major sterol present in animals.
• It occurs exclusively animal in origin.
• Dietary Sources: Liver, Cheese, Meat (Red), Fish, Egg yolk.
• Free cholesterol is amphipathic lipid (polar group is OH at C3)
• Cholesterol ester is non-polar lipid.
• Normal range: Serum cholesterol: 150-200 mg %
70% → cholesterol esters; 30% → free cholesterol

Increased serum cholesterol levels leads to development of

atherosclerosis and myocardial infarction.
 FUNCTIONS OF CHOLESTEROL

1. Component of cell membrane: maintains fluidity of membrane.

• Cholesterol makes membrane fluidity less sensitive to

temperature changes.
• Free cholesterol being polar maintains membrane fluidity but
esterified cholesterol (cholesterol esters) being non-polar
decreases it.
2. Transmission of nerve impulse – As it is a poor conductor of
heat and electricity, it acts as a insulating cover for transmission
of electrical impulse.
3. Synthesis of vitamin D:
4. Source of bile acids and bile salts:
• Required for fat digestion and absorption.
5. Precursor of Steroid hormones:
• Glucocorticoids: Cortisol
• Mineralocorticoids: Aldosterone
• Sex hormones: androgens & estrogen, testosterone
 LIPOPROTEINS
• Conjugated proteins having non-protein prosthetic
group as lipids.
• Need for formation:
As lipids are water insoluble they are transported in aqueous
medium(blood) with the help of proteins.
Arrangement:
• Non polar Lipids (TG and cholesterol): Inner portion
(Core)
• Polar Lipids (PL and free cholesterol): Outer portion
(Periphery)
• Protein: Apolipoproteins
Transport of lipids in plasma is
facilitated by lipoproteins
 APO-LIPOPROTEINS
• The protein part of lipoprotein is called apolipoprotein.
• Some apolipoproteins are integral &cannot be removed
whereas others are bound to the surface & are free to
transfer to other lipoproteins.
Types:
1) Apo A-I: Activates LCAT
2) Apo B100: as it is component of LDL, binds to LDL
receptor on tissues.
3) Apo B48:Major structural apoprotein of chylomicron.
4) Apo C-II: Activates lipoprotein lipase
 Separation of Lipoproteins
1) Ultracentrifugation:
(As per density)

2) Electrophoresis:
(As per charge)
 Plasma Lipoprotein separation on
electrophoresis gel
Origin
-
Chylomicrons
(0.96)

LDL (<1.063) β-Lipoprotein

VLDL (<1.006) Pre-β-lipoprotein

HDL (>1.063) α-Lipoprotein