Lipid- Classification, Structure

and Function
Dr . Rajesh Kumar T
Dept. of Biochemistry
 Food

LIPIDS

PROTEINS

CARBOHYDRATES
 LIPIDs
Lipids (greek: Lipos, fat) are chemically diverse
group of compounds
– Made of hydrocarbons chains
– Characteristic- Insoluble in water but soluble in
organic solvents (chloroform, methanol, benzene,
acetone etc)
Biological Functions of Lipids:
– Stored Energy fuel
– Structural components
– Signaling Molecules, Co-factors and pigments
 Functions of Lipids
1. Storage form of energy fuel (TG)
2. Structural components of cell membrane
3. Hormones (steroid hormones)
4. Signaling molecules, co-factors
5. Surfactants, detergents and emulsifying agents
6. Insulators (subcutaneous fat protect from external
temperature, electric signals (Myelin sheath on
neurons)
7. Help in absorption of fat soluble vitamins (A D E and
K)
8. Minor functions- protect internal organ s by providing
cushioning effect, shape and contour to the body.
METABOLISM

ATP
Grizzly Bear
Camel
Obesity in humans
 Classification of Lipids
LIPIDS Fats (Triglycerides)
(esters of fatty acid and
Simple glycerol)
Esters of fatty acids with
à
Lipids glycerol or other higher alcohols
Waxes- Esters of long
chain fatty acids
and long chain alcohols

Phospholipids (contains
Compound à Esters of fatty acids with phosphoric acid)
Lipids alcohol containing additional gp
Non-Phosphorylated
lipids

Derived Compounds derived from lipids or precursor of lipids

à (e.g., Fatty acids, Steroid hormones, Prostaglandins)
Lipids
 Short-chain Fatty Acid
I. Fatty Acids (less than 6 carbons)

• Carboxylic acids with

hydrocarbon chains ranging
from 3-36 carbon long; Mostly
found as esterified
Medium-chain Fatty Acid
• Insoluble in water (6-10 carbons)
Classification based on length
of carbon chain
• Long-chain, medium-chain,
short-chain
- Commonly occurring FA are Long-chain Fatty Acid
(12 or more carbons)
12-24 carbon atoms and even
number (because usually
synthesized by concatenation
of C2 units)
10
2. Classification based on the Degree of
Unsaturation
 
1. Saturated (C-C)
(All single bonds between
carbons)

2. Unsaturated (C=C)
-Monounsaturated
(one double bond)

-Polyunsaturated
(Two or more
double bond)
Standard Nomenclature:
1) Specifies chain length; 2) number of double bonds, separated
by colon (:) 3) position of double bond
How to assign position of double bond:
- Assign number 1 to carboxyl carbon (C-1) and α (alpha) to the
carbon next to it.
- Position of the double bond is indicated by Δ followed by a
superscript number indicating the lower numbered carbon in the
double bond
- In most monounsaturated fatty acids- double bond located between
C9-C10 (Δ9).
- Double bonds of the PUFA are never conjugated )-CH=CH-CH=CH);
always they are separated by methylene group (CH=CH-CH2-
CH=CH-)
Alternative Nomenclature- PolyUnsaturated Fatty
Acid (PUFA)

- Assign the number 1 to the methyl carbon at the other

end of the chain. This carbon is also designated as
omega (ω)

- If PUFA has first double bond between C3 and C4 it is

called as Omega (ω-3 or n-3) fatty acid-
• Between C6-C7 are called from methyl end=omega-6
(ω-6 or n-6) FA
• The C16 (palmitic acid) and C18 (stearic acid) are most abundant
in body fat.
• Each animal species will have characteristic pattern of fatty acid
composition. Human body fat contains 50% oleic acid(18:1), 25%
palmitic acid, 10% linoleic (18:2) and 5% stearic acid (18:0).
 Omega-3 Fatty Acids-Benefits
• Associated with:
– Anti-inflammatory, Antithrombotic, Antiarrhythmic,
Hypolipodemic, Vasodilatory Properties
• Imbalance of omega-3 and omega-6 (arachidonic
acid) in the diet increases risk of CVD
• Optimal dietary ratio of omega-6 and omega is
between 1:1 to 4:1.
• North American diet- 10:1 to 30:1
• Mediterranean diet rich in leafy vegetable, nuts, fish,
moderate meat is richer in omega-3 fatty acids
Recommended for prevention of Inflammatory
conditions: Ulcerative colitis, Crohn’s; Cardiovascular
disease; Type 2 diabetes; Mental function; Renal
disease; Growth and development
 Your body cannot form Your body can form
C=C double bonds C=C double bonds
before the 9th carbon after the 9th carbon

Omega-3
Fatty acids with
double bond before
the 9th carbon are
ESSENTIAL

Omega-6

Fatty acids with NO

bond before the 9th
carbon are
NONESSENTIAL
 Essential Fatty Acid Deficiency
• Classical symptoms include:
– growth retardation, reproductive failure, skin
lesions, kidney and liver disorders, subtle
neurological and visual problems
• People with chronic intestinal diseases
• Depression
• Attention Deficit Hyperactivity Disorder
– lower levels of omega-3--more behavioral
problems
Structures
Saturated fatty acids
• Fit tightly in regular pattern like crystal structure;
• Strong Van der waal forces between the molecules;
• More thermal energy to disrupt the structure;
• Have high melting point and are solid (waxy);

COOH
COOH
COOH

18
 H H
Unsaturated fatty acids C C
- Cis double bonds introduces kink
- Prevent tight packing of fatty acids
- Needs less thermal energy to disrupt the
structure cis double bond COOH
- Liquid at room temperature

Cis form (bent)

2. Classification
based Saturation

FATTY ACIDS

Saturated FA (C-C) Unsaturated FA (C=C)

Polyunsaturated FA Monunsaturated (FA)

Omega-3 (n-3) FA Omega-6 (n-3) FA

Omega-9 (n-3) FA
Physical Properties of Fatty Acids
• The  most  common  fa-y  acids.  
Carbon Atoms: Common Melting Point
Double Bonds Name (°C)
Saturated Fatty Acids
12:0 Lauric acid 44
Higher mp
14:0 Myr istic acid 58
16:0 Palmitic acid 63
18:0 Stearic acid 70
20:0 Arachidic acid 77
Unsaturated Fatty Acids
Lower mp 16:1 Palmitoleic acid 1
18:1 Oleic acid 16
18:2 Linoleic acid -5
18:3 Linolenic acid -11
20:4 Arachidonic acid -49
Baked food contain hydrogenated fats
 Simple Lipids- Triglycerides
• Triacylglycerols (TAG) or Triglycerides (TG) are neutral
fats and are esters of glycerol with fatty acids

O
ester bonds
CH 2 OH HO C (CH 2)14CH3 Tripalmitin
O O
CH OH + HO C (CH 2)14CH3 CH 2 O C (CH 2)14CH 3 + H 2O
O
O
CH2 OH HO C (CH2)14CH3
CH O C (CH 2)14CH 3 + H 2O
glycerol palmitic acid (a fatty acid) O
CH 2 O C (CH 2)14CH 3 + H 2O

Simple TGs- contain same

1-Stearoyl, 2-Oleoyl, 3-myristoyl glycerol three Fatty acids
O
1 CH
2 O C (CH2)16CH3 Stearic acid Mixed TGs contain- two or
O
three different FA
2
CH O C (CH2)7CH CH(CH2)7CH3
O Oleic acid
3 CH O C (CH2)12CH3 Myristic acid
2
 Physical properties of TGs
- Hydrophobic and insoluble in water

- Oils are liquids at 20oC; They are TG with high

proportion of unsaturated FA; generally plant in
origin.

- Fats are TGs containing high proportion of saturated

FA and are solid or soft solid; Generally animal origin

- TGs containing saturated fatty acids of higher chain

lengths form ‘hard fat’ e.g, Pig fat

- Fat/ TGs containing medium chain triacylglycerols or

unsaturated fatty acids are soft fats e.,g butter,
coconut oil.
 Triglycerides
• Food sources
– fats and oils
• butter, margarine, meat, baked goods,
snack foods, salad dressings, dairy
products, nuts, seeds
– Sources of omega-3 fatty acids
• Soybean, canola, walnut, flaxseed oils
• Salmon, tuna, mackerel
– Sources of omega-6 fatty acids
• Vegetable oils
Fatty Acids in Common Food Fats
 Triglycerides
• Functions: Energy source; Insulation and protection;
Carrier of fat-soluble vitamins
• TGs stored in adipocytes are hydrolyzed into
Fatty acids (FA) and glycerol which are used
a metabolic fuels
• Free fatty acids occur only in trace amounts
in cells
TRIACYLGLYCEROLS ARE HIGHLY
CONCENTRATED ENERGY STORES
•Triacylglycerols (TGs) and glycogen -
two major forms of stored energy
TGs which are more efficient energy stores
because:
(1) They are stored in an anhydrous form
(2) Their fatty acids are more reduced than
monosaccharides.
• 1 g of triacylglycerols stores more than six times as
much energy as a 1 g of glycogen
• Glycogen reserves are depleted in 12 to 24 hours
after eating, triacylglycerols within several weeks.

•Fat breakdown
~50 % of energy in liver, kidney and skeletal muscles
~up to 95 % of energy cardiac muscle
•Fats are the major source of energy:
during fasting as well as in diabetic patient
Storage of Energy as Fat and Obesity

• The triacylglycerols are the storage form of lipids in the

adipose tissue. In a 70 kg normal person, body stores
contain about 11 kg of triacylglycerol, which is roughly
equivalent to 100,000 kcal.

If the same calories were stored as hydrated glycogen,

the total weight of this alone would have been 65 kg!

When stored as TAG, water molecules are repelled and

space requirement is minimal. Excess fat in the body
leads to obesity.
 Chemical Properties: 1. Saponification
• A process by which TGs are hydrolyzed by alkali ( KOH or
NaOH) is known as saponification. The products are glycerol
and Soap (sodium or potassium salt of Fatty acid)
KOH & Heat/Reflux
Fat + water ----------------------------à Fatty acid + Alcohol
Fatty acid + KOH = Potassium Salt of fatty acid + alcohol

e.g. Tristearin (C3H5(OOCC17H35)3 + 3KOHà 3H5(OH)3 + 3C17H35COOK

• Saponification number is defined as the number of milligrams
of potassium hydroxide required to neutralize the fatty acids
formed by complete hydrolysis (saponify) of 1gram of fat.
• It also give indication of molecular weight of fat and is
inversely proportion to Mol weight. i.e., larger saponification
number, the shorter the chains in the fatty acids
– Human fat has saponification number – 194-198
– Butter- 210-230
– Coconut oil- 253-262
 Iodine Number
• Iodine number of fat is defined as the number
of grams of Iodine taken up by 100gm of fat
• Index of degree of unsaturation and directly
proportional to unsaturated fatty acids
• R-CH=CH-R’ + I2------à R-CHI-CHI-R’
• Higher the iodine number- higher is the
unsatuation
• Eg., Iodine number of butter- 28
– Iodine number of sunflower - 130
 Rancidity
• Rancidity refers to unpleasent smell and
tastes of fats and oils
• It is a result of partial hydrolysis of TGs due
to presence traces of hydrolytic enzymes or
oxidation of unsaturated fatty acids.
• Oxidation of unsatuated fatty acids (PUFA)
results in volatiles epoxides and peroxides of
small molecular weight fatty acids.
• Repeated heating of oils lead to to formation
and polymerization of cyclic hydrocarbons.
 Partial Hydrogenation of cooking oils

• To improve shelf life vegetable oil used in cooking, to

increase stability in high temperature, vegetable oil is
subjected to partial hydrogenation
• Partial hydrogenation will increase the melting point.
• Unsaturated fatty acids can be converted to saturated fatty
acids
• Unsaturated compounds react with H2, in presence of Ni or
Pt catalyst : C=C bondsà C–C bond

Unsaturated fatty acid

Hydrogenated fatty
acid (now saturated)
Partial hydrogenation converts Cis To Trans
• Cis double bond to trans double
bound
Cis-fatty acid: H’s on same
side of the double bond; fold into
a U-like formation; naturally
occurring;
Trans-fatty acid: H’s on
opposite side of double bond; more
linear; occur in partially
hydrogenated foods;
 Health effects of Trans fatty acid

• Dietary intake of Trans fatty acid have adverse

effects on health
– Increase risk for cardiovascular diseases
– Increases bad cholesterol

• Deep fried foods such as chips, French fries in

partially hydrogenated oil will have high levels of
trans fatty acid
• Laws to limits the levels of trans fatty acid
 Waxes
• Waxes are the secretion of insects ( bees),
leaves and fruits of plants.
• E.g- Bee wax, whalesperm oil, wool fat
• They are esters of higher fatty acids with
higher monohydroxy aliphatic alcohols.
Long straight chains of 60-100 carbon
atoms.
• Mainly used in ointments, polishes,
cosmetics and candles.
 Compound Lipids-
Phospholipid and Non-phosphorylated lipids

MEMBRANE LIPIDS (POLAR)

Storage Lipids
Phospholipids Glycolipids

Glycero- Sphingolipids Sphingolipids Galactolipids

Triacylglycerols
phospholipids

Fatty Acid Fatty Acid

Fatty Acid
Sphingosine
Sphingosine
Glycerol

Glycerol
Glycerol

Fatty Acid Fatty Acid Fatty Acid Fatty Acid

Fatty Acid
Mono or Mono or
PO4 Alcohol PO4 Choline SO4
Fatty Acid oligosaccharide oligosaccharide
 Phospholipids
Phosphatidic acid
- Derivatives of the parent compound-
Fatty Acid
Phosphatidic acid ( simplest

Glycerol
phospholipid)
Fatty Acid
- Phosphatidic acid is made of Glycerol
X
+ 2 fatty acids esterified to carbon PO4 (polar head
atom 1 & 2 + phosphate group Group)

- Phospholipids are amphipathic have phosphodiester

hydrophobic and hydrophilic portion
Non-polar
Saturated Fatty Acid end
e.g palmitic acid
Glycerol

unsaturated Fatty Acid

e.g Oleic acid

Polar end
 i. Phosphatidylcholine or Lecithin
• Nitrogen containing phospholipid
• The alpha (C1) and beta (C2) carbon position are esterified with
fatty acid; C2 is often esterified with a PUFA; Phosphate on the C3
position is esterified with nitrogen base- called choline
• Phosphatidylcholine is present on inner and outer leaflet of cell
membrane; Specific Phospholipases hydrolyze specific bonds in
Lecithin.

*Lysolecithin- is detergent and hemolytic agent; PLA2 is present viper snake venom
Dipalmitoyl Lecithin - Lung surfactant
• Normal lung function depends on
constant production of lung surfactant
• It prevents of collapse of alveoli by
decreasing surface tension
• Lung surfactant consist of-
– Dipalmitoyl Lecithin
– Phosphatidyl glycerol
– Cholesterol
– Surfactant proteins
• Low surfactant or defect in
biosynthesis of dipalmitoyl lecithin
could lead to respiratory distress
syndrome, major cause of neonatal
morbidity
Phosphatidylethanolamine or cephalin:
– Contains a nitrogen base ethanolamine
– Present in biomembranes and plays a role in blood cephalin
coagulation
Phosphatidylinositol
– Phosphatidic acid is esterified with inositol
– Phosphatidyl inositol bisphosphate or PIP2 is present in
cell membrane and plays vital role as second messenger.
Plasmalogens
Phosphatidylinositol
– Contains alpha-beta unsaturated alcohol (C12 to C18
chain length) linked onto C1 of glycerol
– C2 is esterified to a Fatty acid Plasmalogen
– Phosphoric acid is attached to choline or ethanolamine
– Mainly present in Brain and Muscle
Phosphotidylglycerol
– Two molecules of phosphatidic acid linked with glycerol is
called as cardiolipin, a major mitochondrial membrane.
– Decreased cardiolipin leads to mitochondrial dysfunction
and associated with heart failure, hypothyroidism
Phosphotidylserine
– Contains nitrogen base serine
– Present in inner leaflet of membrane
 Micelles
• Phospholipids are
dispersed in water, their
hydrophobic part keep
away from water forming
molecular aggregates
called micelle.
• This helps in solubilization
of lipids in water and helps
in digestion and absorption
of lipids

• Liposomes: Are spherical

vesicles formed of bilayer
phospholipid .
• It is formed when
phospholipid is mixed with
water under certain
conditions.
• Useful for drug delivery
Cell membranes are phospholipid bilayers
 Spingolipids
- Backbone is spingosine- long aliphatic amino alcohol
- One long chain fatty acids attached to amide linkage to form ceramide
- A polar head (either phosphodiester or glycosidic linkage
Spingosine

Fatty acid

GlycoPhosphospingolipid

Sphingosine
Sphingosine

Phosphospingolipid
Fatty Acid Fatty Acid

Mono or
PO4 Choline oligosaccharide
 Sphingomyelin
• Sphingomyelin is only
Spingosine
sphingophospholipid
Fatty acid
• contain
phosphocholine – a
common sphingolipid
that is prominent in
the myelin sheaths of
neurons.
• The sheath surrounds
and insulates the
axons of neurons.
 1. Glycospingolipids (non-
Glycolipids- phosphorylated lipids
The ceramide is linked with carbohydrate - Contain head group as one or more
High in nervous tissue sugars
- Ceramide + Glucose= Glucocerebroside
- Ceramide + Galatose=
Galactocerebroside
-Occur outer face of plasma membrane

2. Globosides (Ceramide
Oligosaccharides)
Contain two or more hexoses or
hexosamines,
attached to a ceramide
Ceramide + Galactose + Glucose →
Lactosyl ceramide
-Lactosyl ceramide is a component of
erythrocyte Membrane.

3. Gangliosides-
-contain oligosacchardies (3-9 sugars)
and one or more residues- N-
acetylneuraminic acid (sialic acid)
-Cellular recognition
-Cell to cell communication
Glycospingolipids-
The oligosaccharide head
group determines the blood O
groups Antigen

The oligosaccharide head

groups are composed of
- D-glucose (Glc),
- D-galactose (Gal), A
- N-acetyl-D-galactosamine Antigen
(GalNAc),
- Fucose (Fuc).

- The addition of an extra

GalNAc creates the A
antigen/blood type
B
- The addition of a Gal creates Antigen
the B antigen/blood type
DERIVED LIPIDS
 Derived Lipids
• Cholesterol
• Steroid hormones
• Eicosanoids
 E. Sterols: Cholesterol and its derivatives

- Biologically highly important lipid

molecule for animal life existence

Molecular formula: C27H46O.

- Contains steroid rings with a hydroxyl
group (polar group), two methyl groups
and a hydrocarbon tail (non-polar).

- Cholesterol synthesis requires-

Acetyl CoA, ATP, NADPH and O2
18 Acetyl CoA + 18ATP + 16NADPH + 4O2 →
Chlolesterol + 9CO2 + 16NADP + 18ADP + 18P
 Cholesterol Source
1. De novo synthesis in the liver; all the cells have
machinery to synthesize cholesterol, however liver cells are
major producers
2. Dietary – Animal products (e.g., meat, egg); very less or
none in plants
3. In fetus- Major source of cholesterol during embryogenesis
is De novo; however maternal cholesterol is also transferred
to fetus via placenta.
4. Because of the large requirement, highest rate of
cholesterol synthesis occurs during fetus development;
5. Brain – Largest amount - 7mg/gm of tissue; Rest of the
tissues 1.5mg/gm of tissue; major source in brain is de novo
synthesis; blood brain barrier limits transport of cholesterol to
brain
Cholesterol Functions
1. Integral part of cell membrane: Building and
maintenance of cell membrane
• Responsible for FLUIDITY and PERMEABILITY of cell
membranes
 2. Synthesis of Steroid hormones
• Precursor for STEROID HORMONES including
progesterone, testosterone and estradiol  

Progesterone
Cholesterol

Testosterone
Estradiol
 Steroid hormones are derived from cholesterol
(side chain modification and oxidation)
CHOLESTEROL
Adrenal gland:
• Mineralocorticoids- controls the
reabsorption of inorganic ions (Na+, Cl- Pregnenolone
and HCO-3) by the kidney
• Glucocorticoid- help in regulation of
gluconeogenesis and reduce
Progesterone
inflammation.
Testosterone
Male and female Gonads produce Sex
hormones-
• Progesterone – regulates female Corticosterone
reproductive cycle
• Estrogen- Regulates development of Cortisol
(glucocorticoid) Estradiol
female characteristics and organs
• Androgens (Testosterone)- - Regulates
development of male characteristics
Aldosterone
and organs
(mineralocorticoid)
3. Synthesis of Vitamin D
1.UVB in sun light helps to catalyze 7-
dehydrocholesterol to cholecaldiferol
(Vit D3) which is released into blood.

2. Liver converts inactive Vit D3 to

active form 25-hydroxyvitamin D via
hydroxylation

3. Kidney convert 25-hydroxyvitamin

D to 1, 25-hydroxyvitamin D2, another
active form of Vit D.

4. Vit D helps- intestinal absorption of

calcium and iron, magnesium,
phosphate and zinc; for maintenance
of bone health

5. Vit D also helps in immune

regulation; deficiency increases risk to
heart diseases, stroke, infections
4. Synthesis of Bile salts
Lipid  Diges6on  and  Absorp6on    
Mobiliza6on  of  FA  from  TG  into  6ssues  

• 95% of energy of TG
resides in three Fatty
acids
• 5% is contributed by
glycerol
Transport  of  Lipids-­‐  LIPOPROTEIN  
 Transport of Lipid by Lipoproteins
• Cholesterol, cholesterol esters and Triglycerides (TA) are
insoluble in water and cannot be transported in blood or lymph as free
molecules
• These lipids assemble Cholesterol
with phospholipids and Phospholipids
apoproteins
Core containing
(apolipoproteins) to form triacylglycerol
spherical particles called and Cholesterol
LIPOPROTEIN ester

Structure:
Hydrophobic core: - Apolipoprotein
TGs, -
cholesteryl esters
Hydrophilic surfaces: -
cholesterol, -
phospholipids, -
apolipoproteins
 The main classes of lipoproteins
1. Chylomicrons.
2. Very low density lipoproteins (VLDL).
3. Intermediate density lipoproteins (IDL).
4. Low density lipoproteins (LDL).
5. High density lipoproteins (HDL).
 Chylomicrons
• are the largest lipoproteins (180 to 500 nm in diameter)
• are synthesized in the ER of intestinal cells
• contain 85 % of TGs (it is the main transport form of dietary TGs).
• apoprotein B-48 (apo B-48) is the main protein component
• deliver TGs from the intestine (via lymph and blood) to tissues (muscle for
energy, adipose for storage).
• bind to membrane-bound lipoprotein lipase (at adipose tissue and
muscle), where the triacylglycerols are again degraded into free fatty
acids and monoacylglycerol for transport into the tissue
• are present in blood only after feeding

Lympha'c  
exocytosis   vessel  
 VLDL
• are formed in the liver
• contain 50 % of TGs and 22 % of cholesterol
• two lipoproteins — apo B-100 and apo E
• the main transport form of TGs synthesized in the organism (liver)
• deliver the TGs from liver to peripheral tissue (muscle for energy, adipose
for storage)
• bind to membrane-bound lipoprotein lipases (triacylglycerols are again
degraded into free fatty acids and monoacylglycerol)

triacylglycerol

cholesteryl esters
Apo B
Apo E

phospholipids
cholesterol
Lipoproteinlipase – enzyme which is located within
capillaries of muscles and adipose tissue
Function: hydrolyses of TGs of chylomicrons and VLDL.
Formed free fatty acids and glycerol pass into the cells
Chylomicrons and VLDL which gave up TGs are called remnants
of chylomicrons and remnants of VLDL
Remnants are rich in cholesterol esters
Remnants of chylomicrons are captured by liver
Remnants of VLDL are also called intermediate density
lipoproteins (IDL)
Fate of the IDL: -
some are taken by the liver -
others are degraded to the low density lipoproteins (LDL) (by
the removal of more triacylglycerol)
 LDL
LDL are formed in the blood from IDL and in liver from IDL
(enzyme – liver lipase)

LDL are enriched in

cholesterol and
cholesteryl esters
(contain about 50 % of
cholesterol)
Protein component - apo
B-100
LDL is the major carrier
of cholesterol
(transport cholesterol
to peripheral tissue)
Cells of all organs have LDL receptors
Receptors for LDL are localized in specialized regions called
coated pits, which contain a specialized protein called clathrin
Apo B-100 on the surface of an LDL binds to the receptor
Receptor-LDL complex enters the cell by endocytosis.
Endocytic vesicle is formed
LDL uptake by receptor-mediated endocytosis
 HDL
§ are formed in the liver and partially in small intestine
§ contain the great amount of proteins (about 40 %)

§ pick up the
cholesterol from
peripheral tissue,
chylomicrons and VLDL
§ Composed of ApoA-1,
ApoA-II, ApoE
§ enzyme
acyltransferase in HDL
esterifies cholesterols,
convert it to cholesterol
esters and transport to
the liver
 LDL/HDL Ratio

The ratio of cholesterol in the form of LDL to that in the

form of HDL can be used to evaluate susceptibility to
the development of atherosclerosis

For a
healthy
person,
the LDL/
HDL ratio
is 3.5
 High serum levels of cholesterol
cause disease and death by
contributing to development of
atherosclerosis

Cholesterol which is present in the

form of the LDL is so-called "bad
cholesterol."

Cholesterol in the form

of HDL is referred to as
"good cholesterol”

HDL functions as a
shuttle that moves
cholesterol throughout
the body
 Familial hypercholesterolemia
§ congenital disease when LDL receptor are not synthesized (mutation at a
single autosomal locus)
§ the concentration of cholesterol in blood markedly increases
§ severe atherosclerosis is developed (deposition of cholesterol in arteries)
§ nodules of cholesterol called xanthomas are prominent in skin and tendons
§ most homozygotes die of coronary artery disease in childhood
§ the disease in heterozygotes (1 in 500 people) has a milder and more variable
clinical course

atherosclerosis  

xanthomas  
 Eicosanoids
Lipid Mediators- Signaling
 Lipid  Mediators:  Eicosanoids  
• Eicosanoids are 20 C compounds derived mainly from
arachidonic acid (20:4)
• Hormone-like, short- range messengers, affecting
tissues near the cells that produce them- the same
environment in which they are synthesized- paracrine or
autocrine effect
• Eicosanoids refers to
a. Prostanoids- Prostaglandins , Prostacyclins and
thromboxanes
b. Leukotrienes
c. Lipoxins
• Except RBC, all other mammalian cells produce these
eicosanoids
 What are Eicosanoids functions?
Eicosanoids regulated a number of physiological process:
• Fever (PGE)
• Pain (PG)
• Regulate Blood Flow (PG, TXB) : Dilate or constrict
blood vessels and regulate Blood pressure
• Inhibit platelet aggregation important for blood clotting
• Contraction of smooth muscles- GI tract, help during
labor; mediate asthmatic attack.
• Promote or inhibit inflammation or immune response
• Maintain GI mucosal integrity
 Prostaglandins (PGs)
• PGs- First isolated from Prostate tissue by Ulf Von Euler in 1935
(received Noble prize in 1970); Noble prize to Bengt Samuelsson
( biosynthesis of PGs) and Sir Johns Vane ( effect of aspirin on PGs).
• Referred as local hormones because they are present in very low conc
1ng/ml and induce smooth muscle contraction.
• Chemical structure- Derived from 20 carbon cyclic saturated fatty acid,
prostanoic acid.
Classification: PGs classified as different series– A, B, E and F; Differ in
the substituents on the cyclopentane ring.
• Each series can further classified into further as PGE1 ( 1 series, 1
double bond ), PGE2 ( 2 series, 2 double bond), PGE3 ( 3 series, 3
double bond) based on the number of double bonds.
• The primary prostaglandins PGG and PGH, are intermediates in the
synthesis of others
• Only 5 PGs are widely distributed in the body- PGD2, PGE2, {GF2,
and PGI2 ( all are series 2)
 Biosynthesis of PGs
• PGs are derived from PUFA;
– 1 Series PGs derived from Linoleic acid
– 2 series PGs derived from Arachidonic
acid (AA)
– 3 series PGs derived from Eicosa
pentaenoic acid
• Naturally occurring PGs belong 2
series which are derived from AA
incorporated in cell membrane as
phospholipid.
• AA is released from Phospholipid by
action of Phospholipase A2.
• Synthesized by two enzymes-
Prostaglandin H synthase-1
(cycloxygenase 1) and PGHS-2
( COX 2)
• COX-1 (PGS-1) is expressed
constitutively in gastric mucosa,
kidney, platelets, and vascular
endothelial cells. COX-2 (PGS-2) is
inducible and is expressed in COX act on AA and synthesize PGG2 and
macrophages and monocytes in PGH2 as intermediated PGs.
response to inflammation. Subsequently specific enzyme convert
PGH2 to other PGs
 Regulation of PGs synthesis
• PLA2 is activated by epinephrine, thrombin, angiotensin II,
bradykinin and vasopressein, which releases AA
• Steroids inhibit PLA and inhibit AA release from membrane
phospholipid and thereby prevent PGs production
• Cyclo-oxygenase (COX) is activated by catecholamines and
inhibited by Non-steroid anti-inflammatory drugs (NSAIDs). Asprin,
ibuprofen, paracetamol are NSAIDs which inhibit COX
• COX enzyme is suicide enzyme, self catalyzed destruction rapidly
inactivates the enzyme and prevents excessive production of PGs
• COX exist in two forms- COX1( constitutive form) and COX2
inducible form
• COX1 produces prostaglandins that mediate gastric, renal and
platlet functions. The COX2 mediates inflammatory responses
• Prostaglandins have only very short life (~ 30 sec). They are
inactivated by enzyme 15-hydroxyprostaglandin dehydrogenase
 Biological Activity of Arachidonic Acid Metabolites
Generated During Inflammation
 
• PGI2 (Prostacyclin) and PGE2
– inhibits platelet aggregation and protects the blood vessel wall
against platelet deposition and reduces risk for CVD
– induces vasodilatation and lowers blood pressure
– suppress inflammatory cell activation
• Thromboxane (TXA2)
– induces platelet aggregation
– induces vasoconstriction
• Prostacyclin and thromboxane have opposing activity.
• PGF is constrictor of bronchiole smooth muscle
• PGE is a potent bronchodilator
• PGE2 and D2 are potent inducers of inflammation by
increasing capillary permeability. Erythema and wheal
produced at the site of injury.
• Therefore, inhibition of PGs by aspirin and cortisol produces
anti-inflammatory effects.
 The Leukotrienes are identified as LTs
are produced by leukocytes (WBC e.g
neutrophil, macrophages) from AA in
Leukotrienes
response to immunologic and non-
immunologic stimuli. Synthesis

• The leukotrienes LTC4, LTD4 and

LTE4 are known as the
peptidoleukotrienes or the cysteinyl
leukotrienes; collectively are
referred as slow reacting
substance of anaphylaxis
• Functions:
- cause smooth muscle
contraction
- constrict the bronchioles
- increase capillary
permeability
- activate leukocytes
- produce vasoconstriction

• Mediators of Asthma
 Lipoxins

- Lipoxins are a family of conjugated

tetraenes also arising in leukocytes.

- The lipoxins are synthesized through the

sequential actions of 5-LOX in leukocytes
followed by 12-LOX action in platelets.

- Function- Anti-inflammatory and decrease

immune response
 Pathways of arachidonic acid (AA) release and Non steroidal
metabolism. antiinflammatory
drugs (NSAID)
e.g., Aspirin,
ibuprofen,
paracetmol
Linear Cyclic
pathway pathway
Significance of Omega-3 and Omega-6 PUFAs
• Omega 3 PUFA - unsaturation (double bond) between
3rd and 4th carbon from omega end.
– Three major types of omega-3 fatty acids in food are- Alpha
linolenic acid (ALA), eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA).
– The body converts ALA to EPA and then to DHA. Nuts and fish
are rich in Omega 3 FA.
• Omega 6 PUFA (double bound starting at C6-C7)
– Main source is vegetable oils- soybean oil, corn oil.
– Gamma Linoleic acid, major omega 6 FA; is converted to
arachidonic acid, which is important omega 6 PUFA.
• Omega 3 and omega 6 fatty acids consumed are
incorporated into cell membranes in all tissues in the
body and serves precursor for synthesis of Eicosanoids
that regulate development and inflammation
 Omega 3 Fatty acids (EPA, DHA)- produces Anti-inflammatory eicosanoids
Omega 6 ( AA) – produces pro-inflammatory mediators

eicosapentaenoic acid (EPA) and

docosapentaenoic acid (DHA
Thanks….