CHEMISTRY OF LIPIDS

By
Behailu Tsegaye
 TOPIC CONTENT IN LECTURE

Definition Simple lipids

Classification Complex lipids

Biological importance Derived lipids

 Objective
• At the end of this lecture you should be
 Classify lipids
Introduce the biological function of lipids
Identify different component and classification of
lipids behavior
 INTRODUCTION

 What is Lipids?

 The word lipids is derived from the Greek word 'lipos' meaning
fat.
 Lipids are a large and heterogeneous organic compounds that are
related more by their physical than by their chemical properties
 It is insoluble in water but soluble in non-polar organic solvents
like chloroform, ether , benzene, hexane, acetone, etc
 The lipids found in biological systems are either hydrophobic
(nonpolar groups) or amphipathic (polar and nonpolar groups)
 Lipid Chemistry cont..

• Majority of the lipids are formed by esterification of an

alcohol with one or more fatty acids
• It is components of living systems consisting of basically
carbon, hydrogen and oxygen; in addition some have
nitrogen,carbohydrates and phosphorus
• It is widely distributed in nature, both in plants and in animals,
and differ from other organic compounds in their potential to
be utilized by the living organisms
 Bloor’s Criteria
• According to Bloor, lipids are compounds having the
following characteristics:
 They are insoluble in water
 Solubility in one or more organic solvents, such as
ether, chloroform, benzene, acetone, etc, so called fat
solvents
 Possibility of utilisation by living organisms
 Occurrence

•Fats and oils are widely distributed in nature in both

plant and animal tissues.
•They occur in relatively high concentration in seeds
of certain plants (oil-seeds) where they function to
supply food for use of the growing seedlings.
•Animals store deposits of fats in their adipose tissues;
these stored fats constitute a reserve which can be
used as the source of energy
 FUNCTIONS OF LIPIDS
Structural
component Protection
Storage Act as thermal
of cell of internal
form of insulator (Act as
membrane Precursor organs by
energy electric insulators in
and of many providing
neurons)
9Kcal/g nervous steroid a
tissue. hormones, Provide insulation
(triglyceri cushionin
vitamin D against changes in
des) (phospholi g effect
external temperature
pids and (pads of
(subcutaneous fat)
cholesterol fat)
)
 FUNCTIONS OF LIPIDS

Fats serve as
Helps in surfactants by
absorption of reducing surface
Improve taste
fat soluble Lipoproteins tension. As
transporting lipids detergents and and palatability
vitamins A, D, E emulsifying of food .
and K from agents (amphipathic
intestine lipids)

 Can be stored in the body in almost unlimited amount in the form

of triacylglycerol in contrast to carbohydrates.
 It is Metabolic regulators (steroid hormones and prostaglandins)
 Inherited lipid disorders:

• Several inherited and acquired diseases,

• Excessive fat deposits cause obesity, Truncal obesity is
a risk factor for heart attack
• Abnormality in cholesterol and lipoprotein metabolism
leads to atherosclerosis, cardiovascular diseases, lipid-
storage diseases, fatty liver, infertility, and respiratory
distress
• In diabetes mellitus, the metabolisms of fatty acids and
lipoproteins are deranged, leading to ketosis
 CLASSIFICATION OF LIPIDS
According to their composition, lipids can be classified
into three categories

Complex Derived
Simple lipid
lipid lipids
Simple lipids

• Simple lipids are esters of fatty acids with fatty alcohols.

• They are sub-classified according to the type of alcohol used

into neutral fats and waxes.

e.g., Triacylglycerols e.g cetyl alcohol (C16H33OH)

 Neutral fats

• They are naturally occurring esters of glycerol with various fatty acids
• To be esterified, in vivo, glycerol is first activated into glycerol-3-
phosphate by an enzyme glycerokinase and fatty acids are activated into
fatty acyl-CoA by specific synthetases.
• The neutral fats are the most abundant lipids in nature constituting ~98%
of adipose tissue lipids, 30% of the plasma and liver lipids and less than
10% of erythrocyte lipids. Major fatty acids in animal fats include palmitic,
stearic and oleic acids.

O Fatty acid O
CH2 OH HO C CH2 R1 CH2 O C CH2 R1
Fatty acid O
3H2O O
R2 CH2 C OH OH CH R2 CH2 C O CH
O Fatty acid O
CH2 OH HO C CH2 R3 CH2 O C CH2 R3
Glycerol A triglyceride (Triacylglycerol)
 Cont..
• Simple triacylglycerols contain the same fatty acids or mixed
triacylglycerols
• Naturally occurring fats are mostly of the mixed type

O Palmitate O Palmitate
CH2 O C (CH2)14 CH3 CH2 O C (CH2)14 CH3
Palmitate O Oleate O
H3C (CH2)14 C O CH H3C (CH2)7 CH CH (CH2)7 C O CH
O Palmitate O Stearate
CH2 O C (CH2)14 CH3 CH2 O C (CH2)16 CH3
A simple Triacylglycerol (Tripalmitin) A mixed Triacylglycerol (1-palmito-2-oleo-3-stearin)
 Storage of Energy as Fat

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.

The long chains of fatty acids are extraordinarily for energy

storage, because they contain Carbon in a fully reduced form
and will therefore yield a maximum amount of energy on
oxidation.
Lower melting points of oils are mainly due to the presence of a larger
percentage of unsaturated fatty acids
 Physical properties of fats and oils

•It is colorless, odorless and tasteless; however, associated substances

may give them specific color and flavor, e.g., yellow pigmentation of
the body fat or milk fat is due to associating carotenes and bilirubin.
•Solubility: They are insoluble in water but soluble in
organic fat solvents.
•Specific gravity: The specific gravity of all fats is less
than 1.0, consequently all fats float in water
•Emulsification: Emulsions of fat may be made by shaking vigorously
in water and by emulsifying agents such as gums, soaps and proteins
which produce more stable emulsions.
 Chemical properties of fats and oils
• Hydrolysis

• The fats may be hydrolysed with:

• Super heated steam,
• By acids, or alkalies, or
• By the specific fat spliting enzymes lipases
 Hydrolysis by Lipases
• Sites: Lipases are found in human body in following places

(a) Lingual lipase in saliva,

(b) gastric lipase in gastric juice,
(c) pancreatic lipase in pancreatic juice,
(d) intestinal lipase in intestinal epithelial cell,
(e) adipolyticlipase in adipose tissue, and
(f) serum lipase.
Pancreatic lipase is peculiar in that it can hydrolyse ester bonds in positions 1 and 3
preferentially, than in position 2 of TG molecule.
 Hydrolysis of Triglycerides

 This occurs in the body during digestion of dietary fat

and mobilization of TAG from adipose tissue.
 Triglycerides in the body are hydrolysed by enzymes,
lipases
 Triacyl glycerol is sequentially hydrolysed to
diacyl glycerol and mono acyl glycerol and finally
glycerol plus 3 fatty acids
Hydrolysis of triglycerides
 cont..

 Saponification
 When triglycerides are hydrolysed by alkali, the process is known
as saponification.
 The products are glycerol and soaps
 Saponification number is defined as the number of milligrams of
potassium hydroxide required to saponify one gram of fat.
• It is an indication of the molecular weight of the fat or measure of
the chain length of fatty acids in the fat
• Human fat has a saponification number of 194-198, butter has 210-
230 and coconut oil has 253-262.
 Thus, fats containing short-chain acids will have more carboxyl groups
per gram than long chain fatty acids and consume more alkali, i.e., will
have higher saponification number.
 Saponification

 Alkaline hydrolysis produces glycerol and salts of

fatty acids (soaps).
 Soaps cause emulsification of oily material this help easy
washing of the fatty materials
O O
H 2C R1 C
CH2 O C
OH
R + ONa
R1 O O
2 O O
CH 3 HOH2C
C H R2 O
2 C
CC O C H OH R3 C
R3
NaOH Glycerol Sodium
ONa salts of
ONa
Triacylglycerol fatty acids
(soap)
Saponification
 Rancidity of Fat
• Fats and oils have a tendency to become rancid.
• The term rancidity refers to the appearance of an unpleasant smell
and taste for fats and oils.
• Exposure to atmospheric oxygen, light, moisture, heat or bacterial
or fungal contamination can cause rancidity. Rancidity
decomposes unsaturated fatty acids into toxic products and
destroys the associated fat-soluble vitamins.
• Hydrolytic rancidity
• It is due to partial or slight hydrolysis of fats into free fatty acids
and glycerol by contaminated bacterial lipase in presence of high
temperature and moisture. Release of volatile short-chain fatty
acids causes the unpleasant odor.
 O O
H2 C R1 C
CH2 O C
OH
R2 + R OH
R1 2 C
O O
O
CH O HOH C H OH O
2 3 H2 2C
R3 C
O OH
Glycerol
C Free
OHfatty acids
Lipase (volatile, bad
RC
3
OC H
odor)
Triacylglycerol
Oxidative Rancidity:

 Oxidative rancidity is the result of partial oxidation of unsaturated

fat or oil, by exposure to oxygen, light and/or heat, producing
peroxide derivatives which on decomposition give substances,
e.g., epoxides, peroxides, aldehydes, ketones, free radicals and
dicarboxylic acids that are toxic and have bad odor.
 This occurs due to oxidative addition of oxygen at the
unsaturated double bond of unsaturated fatty acid of oils.
 The same process, if it occurs in vivo will affect the integrity of
biomembranes, leading to cell death.
Ketonic Rancidity:

 It is due to the contamination with certain fungi such as

Asperigillus Niger on fats such as coconut oil.

 Ketones, fatty aldehydes, short chain fatty acids and fatty

alcohols are formed.

 Moisture accelerates ketonic rancidity.

Rancidity of Fat cont..
• Many natural fats and oils may contain antioxidants (e.g. vitamin
E, phenols, naphthols, hydroquinones,tannins), which prevent
the occurrence of oxidative rancidity.
• polyunsaturated fatty acids (PUFA) are more easily oxidized;
so vegetable oils with a high content of PUFA are usually
preserved with addition of antioxidants.
• Repeated heating of oils would lead to the formation and
polymerisation of cyclic hydrocarbons.
• These will impart an unpleasant taste and color to the oil.
• Saturated fats resist rancidity more than unsaturated fats and
oils.
 Iodine Number

• Iodine number of a fat is defined as the number of grams

of iodine taken up by 100 grams of fat.
 Unsaturated fatty acids absorb iodine at their double
bonds, therefore, as the degree of unsaturation increases
iodine number and hence biological value of the fat
increase.
• It is an index of the degree of unsaturation and is directly
proportional to the content of unsaturated fatty acids.
• Higher the iodine number, higher is the degree of
unsaturation
• e.g. iodine number of butter is 28, and that of sunflower oil is 130
 Hydrogenation or hardening of oils

 It is a type of addition reactions accepting hydrogen at the double

bonds of unsaturated fatty acids.
 The hydrogenation is done under high pressure of hydrogen and is
catalyzed by finely divided nickel or copper and heat.
 It is the base of hardening of oils (margarine manufacturing), e.g.,
change of oleic acid of fats (liquid) into stearic acid (solid).
 It is advisable not to saturate all double bonds; otherwise margarine
produced will be very hard, of very low biological value and
difficult to digest.
Li(+)2H (+)2H (+)2H
• nolenic —→ Linoleic —→ Oleic —→ Stearic
 Halogenation

 Neutral fats containing unsaturated fatty acids have the ability of

adding halogens at the double bonds.
 It is a very important property to determine the degree of
unsaturation of the fat or oil that determines its biological value

CH 3 (CH 2 ) 4 CH CH CH 2 CH CH (CH 2 ) 7 COO H

Linoleic acid
2 I2

CH 3 (CH 2 ) 4 CH CH CH 2 CH CH (CH 2 ) 7 COO H

I I I I
Stearate-tetra-iodinate
 Melting Point

• The short and medium chain fatty acids are liquids, whereas long
chain fatty acids are solids at 25 oC.

• The solubility in water decreases, while melting and boiling points

increase, with increase in chain length.
• The unsaturated fatty acids have lower melting point compared to
saturated fatty acids with the same chain length.
• For example, stearic acid (C18 fatty acid, no double bond) has the
melting point 69oC, oleic acid (C18, 1 double bond) has 13oC;
linoleic acid (C18, 2 double bonds) has –5oC and linolenic (C18,
3 double bonds) has –10oC.
 Salt Formation

• Saturated and unsaturated fatty acids form salts with alkali.

• CH3—COOH + NaOH → CH3—COONa + H2O
• Sodium and potassium salts of long chain fatty acids are
called soaps.
• Calcium and magnesium soaps are insoluble.
• Calcium soaps are used in grease.
• Alkyl sulfate (R—CH2—O—SO2—ONa) and alkyl
sulfonate (R—CH2—SO2—O—Na) are not precipitated
by hard water and are used as detergents.
 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 .

• Glycerol + fatty acid → Mono acyl glycerol

• Monoglyceride + fatty acid → Di acyl glycerol
• Diglyceride + fatty acid → Triglyceride or tri acyl glycerol
Oxidation of Fatty Acids

 All fatty acids undergo oxidation in the body to give

energy.

 Beta-oxidation is the major process by which acids are

oxidized.

 However, the unsaturated fatty acids can undergo auto

oxidation, due to the presence of the highly reactive
double bonds and a variety of products.
 WAXES
 widely distributed in plants, insects and animals
 Esters of long-chain FA with higher molecular weight monohydric alcohols
than glycerol
 Alcohols in waxes include cholesterol, vitamins A and D, mericyl and cetyl
alcohols.
 It have very long straight chains of 60-100 carbon atoms.
 They are hard solids at room/physiological temperature. They are soluble only
in fat solvents
 It is indigestible and no nutritional value, but are very resistant to rancidity.
 It used as the base for the preparation of cosmetics, ointments, polishes,
lubricants and candles
EXAMPLES
 Lanolin
 Beeswax
 Whale sperm oil
 COMPLEX LIPIDS
When a lipid contains an element or moiety in addition to fatty
acids and alcohol present in simple fats, it is known as a
compound or conjugated lipid.

Subclassified according to the type of prosthetic group

phosphorus Carbohydrate Proteins

(Phospholipids) (Glycolipids) (Lipoproteins)
 Phospholipids
• In phospholipids, the additional group is a phosphoric acid
moiety.
• They are composed of fatty acids and a compound of alcohol
with phosphoric acid.
• All cellular and sub-cellular membranes of plant and animal
cells are made up of phospholipids
• They are further classified, according to the alcohol moiety,
into
 Glycerophosphatides,
 Sphingophosphatides and
 Phosphoinositides
 PHOSPHOLIPIDS
FA + ALCOHOL + PHOSPHORIC ACID

They are composed of the fatty alcohol (glycerol, inositol or sphingosine), fatty acids
(saturated and polyunsaturated), and a phosphate group to which a nitrogenous base, i.e.,
choline, serine, threonine, or ethanolamine is attached.

They
frequently
have
nitrogen
containing
bases
 Importance of phospholipids

1.Majority of organelle membranes are composed of phospholipids and

transport of substances through these membranes is controlled by
properties of phospholipids.

2.The liver, brain and blood cells are richer in phospholipids.

3.They are lipotropic agents, i.e., they help in mobilization of fats from liver
to the peripheral tissues. Excessive accumulation of fats in liver is known
as fatty liver, which is a predisposing condition for atherosclerosis.

4.Myelin sheath of nerves is rich in phospholipids.

 Cont..
5. They are important for excretion of cholesterol into bile and digestion and
absorption of neutral lipids.
6. They are important components in blood clotting and platelet aggregation.
7. They are important components of the surfactants of lung alveoli that prevent
its irreversible collapse and neonatal respiratory distress syndrome.
8. They play important role in signal transduction across the cell membrane.
 PHOSPHOLIPIDS

Phospholipids
may be
classified on the
basis of the
type of alcohol
present
A. Glycerophospholipids B. Spingophospholipids
ALCOHOL IS GLYCEROL ALCOHOL IS SPINGOSINE

 Phosphatidylcholine
 Phosphatidyl
ethanolamine
 Spingomyelins
 Phosphatidyl serine
 Phosphatidyl inositol
 Plasmalogens
 Cardiolipins
Glycerophosphatides

• It derivatives of phosphatidic acid,

which is the simplest phospholipid.
• Phosphatidic acid is made up of one
glycerol to which two fatty acid
residues are esterified to carbon atoms
1 and 2. The 3rd hydroxyl group is
esterified to a phosphoric acid.
• The phosphate on carbon C3 may be
further attached to a nitrogen base like
choline, ethanolamine and serine
Phosphatidyl choline or
Lecithin
i. This is a nitrogen containing
phospholipid
ii. The alpha and beta positions
are esterified with fatty acids.
Usually the fatty acid attached to
the beta-carbon is a PUFA
molecule
iii. The phosphoric acid is added
to the third position, to form
phosphatidic acid. The
phosphate group is esterified to
the quaternary nitrogen base,
Choline.
 Phosphatidyl ethanolamine or Cephalin

• Cephalin differs from lecithin in

that the nitrogen
base ethanolamine is present
instead of choline
• Cephalin is also found in
biomembranes and possesses
amphipathic properties.
 Phosphatidyl inositol
Inositides contain another cyclic sugar
alcohol, i.e., inositol along with the glycerol.
• It is present in biomembranes
• This compound plays
a vital role in the mediation of hormone
action on biomembranes
• It plays a major role as second messengers
during signal transduction for certain
hormones
 Sphingophospholipids
 The 18-carbon unsaturated amino alcohol sphingosine is the
alcohol instead of glycerol.
 Sphingomyelins:
 It is found in large amounts in bio membranes of brain, nerves and
in smaller amounts in lung, spleen, kidney, liver and blood.
 Sphingomyelins are the only sphingolipid that contain
phosphate and have no sugar moiety
 The types of fatty acids present in sphingomyelins may be stearic,
nervonic, or lignoceric acids in brain and nerves, and palmitic or
lignoceric acids in spleen and lungs.
 SPHINGOPHOSPHOLIPID
 The compound composed
of sphingosine, fatty acid,
phosphate and choline is
known as sphingomyelin,
whereas the molecule
without choline is known
as ceramide.
 Ceramides have been
found in the free-state in
the spleen, liver and red
Sphingomyelin
cells.
 Niemann-Pick disease

• It is a rare hereditary fatal disease that occurs in infants with neuropathic

disorder and hepatosplenomegaly.
• It is due to abnormal accumulation of sphingomyelins in the liver, spleen and
brain tissues caused by hereditary deficiency of a lysosomal enzyme,
sphingomyelinase. The enzyme is involved in regular turnover of the
sphingomyelins; therefore, in its absence, the sphingomyelins cannot be
metabolized and get accumulated. Clinically, the patients present with
enlargement of abdomen, liver and spleen. The children show progressive
mental retardation and majority of them die within two years.
 Phosphatidyl Glycerol (Cardiolipins)
• It is formed by esterification two
molecules of phosphatidic acid to 3
molecules glycerol and 4 fatty acids it can
form Diphosphatidyl glycerol or
cardiolipin O OH
R1 CH2 C O CH2 C Phosphatidate
CH2 O P O H2
• They are found in the inner membrane of O O C O C CH R
H 2 2
R2 CH2 C O CH CH OH
mitochondria, initially isolated from heart O O
Phosphatidate CH2 O P O CH2 C O C CH R
muscle. Glycerol H 2 2 1
OH O
• Decreased cardiolipin level leads to Cardiolipin
mitochondrial dysfunction, and is
accounted for heart failure,
hypothyroidism and some types of
myopathies
 Plasmalogens

• These are phospholipids which have an

aliphatic long chain α − β unsaturated alcohol
in ether linkage with the first hydroxyl group
of glycerol
• The second OH group is esterified to a fatty
acid.
The phosphoric acid is attached to choline or
ethanolamine
• The alcohols have about C12 to C18 chain
length.
• Plasmalogens are found in biomembranes in
brain and muscle.
 Glycolipids

Lipids containing carbohydrate moiety are called glycolipids.

They contain a special 18-carbon, alcohol called sphingosine

or sphingol and nitrogenous base in addition to fatty acids but
does not contain phosphoric acid or glycerol.
These are of two types:
• Cerebrosides
• Gangliosides
 GLYCOLIPIDS
 They are lipids that contain carbohydrate residues with
sphingosine as the alcohol and a very long-chain fatty acid
(24 carbon series)

FA + ALCOHOL[SPINGOSINE] +CARBOHYDRATE
WITH NITROGEN BASE

 They do not contain phosphate group or glycerol.

The carbohydrate like glucose, Example
galactose, mannose, fucose, N- Cerebrosides
acetyl-glucosamine or N-acetyl- Gangliosides
galactosamine, etc
 GLYCOLIPIDS
 Cerebrosides:- They occur in myelin sheath of nerves and
white matter of the brain tissues and cellular membranes.
• They are important for nerve conductance.
 Gangliosides:-They are more complex glycolipids that occur
in the gray matter of the brain, ganglion cells, and RBCs
They transfer biogenic amines across the cell membrane
and act as a cell membrane receptor
 Lipoproteins

It is composed of simple or compound lipids associated with

proteins e.g., plasma and membrane lipoproteins.
Lipoproteins used as transport vesicles to transport water-
insoluble lipids in serum
• Based on their density, the liporoteins of blood plasma are
classified into 4 classes.
• Density of a lipoprotein is inversely related to the lipid
content.
 CLASSIFICATION
Chylomicrons
Chylomicrons
LIPOPROTEINS
Very
Verylow
lowdensity
densitylipoproteins
lipoproteins- VLDL
- VLDL
Intermediate
Intermediatedensity
densitylipoprotein
lipoprotein– –IDL
IDL
Low
Lowdensity
densitylipoprotein
lipoprotein– –LDL
LDL
High
Highdensity
densitylipoprotein
lipoprotein- HDL
- HDL
Lipid with
prosthetic
group PROTEIN
 Functions of Lipoproteins
• Lipoproteins are involved in the transportation of lipids in the
body.
• Chylomicrons: They transport dietary or exogenous
triglycerides from intestine to liver.
• Very low density lipoproteins (VLDL): They are involved in
the transport of endogenous triglycerides from liver to extra
hepatic tissues.
• Low density lipoproteins (LDL) : LDL is the major vehicle for
the transport of cholesterol from liver to extra hepatic tissues.
• High density lipoproteins (HDL) : HDL is the major vehicle for
the transport of cholesterol from extra hepatic tissues to the liver.
 Derived lipids

• They are products of hydrolysis of simple or compound lipids,

and their derivatives.
• They may be categorized as follows
 Diglycerides, monoglycerides, fatty acids, alcohols and
aldehydes
 Bile acids, hormonal and vitamin derivatives of cholesterol
 Fatty acid derivatives, e.g., eicosanoids (prostaglandins,
leukotrienes and thromboxanes).
 Ketone bodies
 DERIVED LIPIDS
Derived from lipids (simple or complex)or precursors
of lipids

Example

Vitamin A
Steroids Cholesterol Fatty acids
and D
 Steroids and Sterols
1. The steroids are often found in association with fat.
2. They may be separated from the fat, after the fat is saponified,
since they occur in unsaponifiable residue because they contain no
fatty acids and they cannot form soaps.
3. All of the steroids have a similar cyclic nucleus resembling
phenanthrene (ring A, B and C) to which a cyclopentane ring (ring
D) is attached. It is designated as cyclopentano perhydro-
phenanthrene nucleus
4. Methyl side chains occur typically at positions 10 and 13
5. A side chain at position 17 is usual.
If the compound has one or more –OH groups and no carbonyl or
carboxyl groups, it is called a ‘sterol’ and Most important sterol in
human body is cholesterol.
Cyclopentano-perhydro-phenanthrene nucleus
 Biologically Important Steroids
• Sterols – Cholesterol, ergosterol, lanosterol
• Bile Acids – Cholic acid, Glycholic acid
• Adrenocortical Hormones – Costicosterone,
cortisol, aldosterone
• Sex hormones – Androgen, Estrogen
• Vitamins – Vitamin D, K
 STEROLS OF BIOLOGICAL IMPORTAN
• 7-Dehydrocholesterol
It is an important sterol present in the skin. This differs from cholesterol only
in having a second double bond, between C7 and C8
Source: In man, 7-dehydrocholesterol may be obtained partly by synthesis
from cholesterol in skin and/or intestinal wall.
• In the epidermis of skin, UV rays of sunshine change 7-dehydrocholesterol
(pre-cholecalciferol) to cholecalciferol (vitamin D3). Hence 7-
dehydrocholesterol is called as provitaminD3

7-Dehydrocholesterol (Provitamin D 3)
 Ergosterol (Provitamin-D 2)
• Structurally this sterol has the same nucleus as 7-dehydrocholesterol but differs
slightly in its side chain
• When irradiated with UV rays (long wave 265 μm) ergosterol is changed to
vitamin D 2 by the opening of the ring B of the sterol.
• Hence ergosterol is called as Provitamin-D2, overirradiation may produce toxic
products

Ergosterol (Provitamin-D 2)
 Vitamin D
• Vitamin D2 Vitamin D3
 CHOLESTEROL
 Structure
• Cholesterol is the most important sterol in human body.
• Its molecular formula is C27H45OH.
• It possesses “cyclo-pentane-perhydro-phenanthrene
nucleus”.
• It has an –OH group at C3.
• It has an unsaturated double bond between C 5 and C 6.
• It has two –CH 3 groups at C10 and C13
• It has an eight carbon side chain attached to C17.
CHOLESTEROL
 Source and occurrence of Cholestrol
— Source
 It is synthesized in the body from acetyl-CoA (1gm/day) and is also taken in
the diet (0.3 gm/day ) as in, butter, milk, egg yolk, brain, meat and animal fat).
 Occurrence
 It is widely present in body tissues. e.g., adrenal cortex content is 10%,
whereas, brain is 2%, nervous tissue 2 %, liver 0.3%, skin 0.3 % and
Intestinal mucosa 0.2 %, others 0.2-0.3%.
 Cholesterol
• In skin may be related to vit D formation by UV rays
• In the adrenal gland and gonads to steroid hormone synthesis
• In blood and bile and is usually a major constituent of gallstones
 Property of Cholesterol
 It is White or faintly yellow colour
 Odourless,
 Insoluble in water, sparingly soluble in alcohol
 Soluble in ether, chloroform, hot alcohol, ethyl
acetate and vegetable oils.
 It is not saponifiable
 Its melting point is 147 to 150o C.
 It can make halogen rxn on its unsaturated bond
 FUNCTIONS OF CHOLESTEROL

It is the most important sterol in animal tissues as free alcohol or in an esterified form
(with linoleic, oleic, palmitic acids or other fatty acids)
1.Precursor for Steroid hormones synthesis in the body.
a. Progesterons
b. Glucocorticoids
c. Mineralocorticoids
d. Androgens & Estrogens
3.Formation of Bile acids and bile salts.
3.Synthesis of Vitamin D
4.widely distributed in cells particularly in the nervous tissue
5.Cholesterol and its esters are important components of cell membrane and lipoproteins
 CHOLESTEROL CONT..
 Forms of cholesterol:
 Cholesterol occurs both in free form and in ester form, in which
it is esterified with fatty acids at –OH group at C3 position.
 The various fatty acids, which form cholesterol esters, are as
follows
• Linoleic acid 50%
• Oleic acid 18%
• Palmitic acid 11%
• Arachidonic acid 5%
• And other fatty acids 16%
• About one gram of cholesterol is synthesized per day in the body
 Cholesterol esters formation

• Some cholesterol esters are formed in tissues by the transfer of

acyl groups from acyl-CoA to cholesterol by acyl transferases.
• Majority of esterification of cholesterol in plasma takes place
with the help of an enzyme Lecithin-cholesterol acyl transferase
(LCAT), which transfers a fatty acyl unit from lecithin to free
cholesterol to form cholesterol ester.
CHOLESTEROL ESTER
 Norum’s disease
• The inherited deficiency of LCAT causes a disease
known as Norum’s disease. The disease is characterized
by corneal opacity (cataract), anemia and proteinuria.
• Norum’s disease: A genetic deficiency of LCAT
produces
Norum’s disease due to the failure of esterification of
cholesterol at the cost of lecithin. The disease is
characterised by:
• Rise in free cholesterol ↑
• Rise in lecithin in plasma ↑ and
• Fall in cholesterol ester↓, lysolecithin ↓ and
α-lipoproteins ↓ in plasma
 CHOLESTEROL CONT..
Cholesterol is the major sterol in animal tissues.
No vegetable oil contains any cholesterol.
Only a little portion of the body cholesterol is derived
from diet. The bulk of it is synthesized in the body.
Unsaturated fatty acids lower blood cholesterol levels by

controlling cholesterol’s synthesis as well as its

elimination from the body.
 Cholesterol Accumulation
 Accumulation of cholesterol in arteries is responsible for the initiation of
plaque formation leading to coronary artery disease
 Excessive deposition of cholesterol in gall bladder can give rise to
gallstones (Cholilethiais).
 Intestinal bacteria reduce cholesterol into coprosterol (fecal sterol) and
dihydrocholesterol. It may be reabsorbed in an enterohepatic circulation.
 Cholesterol may be conjugated with glucuronic acid and excreted in
urine in small amounts.
 In plasma, the total cholesterol amount is ~200 mg/dL, of which 2/3 is
esterified, to unsaturated fatty acids while the remainder occurs as the
free cholesterol.
 Cholesterol Accumulation cont..
• Both dietary cholesterol and that synthesized de novo ( which is the major source
of body cholesterol) are transported through the circulation in lipoprotein
particles
• The synthesis and utilization of cholesterol must be tightly regulated in order to
prevent over-accumulation and abnormal deposition within the body.
• Of particular importance clinically is the abnormal deposition of cholesterol and
cholesterol-rich lipoproteins in the coronary arteries.
• Such deposition, eventually leading to atherosclerosis (athero=arteries,
sclerosis=thicking), is the leading contributory factor in diseases of the coronary
arteries.
• The statins (drugs given to lower blood cholesterol) inhibit de nevo cholesterol
synthesis. Statins currently in use include atorvastatin, simvastatin, and
pravastatin
 FATTY ACIDS
• It is the most common abundant derived 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
of fat by hydrolysis rxn
• They are mainly straight chain, aliphatic, monocarboxylic acids, ranging
in chain lengths from 4 -24 C atoms
• Have the general formula, R—CO—OH, and Depending on the R group
(the hydrocarbon chain), the physical properties of fatty acids may vary
• They are the building blocks of the several classes of lipids and neutral
fats, phosphoglycerides, glycolipids, cholesterol esters and some waxes.
 FATTY ACIDS cont..

• Fatty acids may be saturated or unsaturated

• Therefore, unsaturated fatty acids show geometrical isomerism
and exist as ‘cis’ and ‘trans’ isomers.
• The cis-form is the natural form, whereas, the trans-form is
toxic and is produced during hydrogenation of liquid vegetable
oils and processing of fast foods.
• An example is the cis-oleic acid and its trans-form, elaidic
acid.
Fatty Acids
 Nomenclature of Fatty acids
• Fatty acids are simple linear hydrocarbon chain mono-
carboxylic acids containing a carboxylate group at one
end (by convention, the numbering of carbon starts at
this end is named C1) and may have one or more
double bonds.
• Common numbering system of fatty acids uses Greek
letters for the carbon atoms, therefore, the carbons
starting from the carboxylic end are labeled as α, β, γ, δ
and the terminal methyl as ω atoms.
 Numbering of carbon atoms in FA

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1
CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH

ω δ γ β α
Palmitic acid

Methyl end Carboxyl end

 Nomenclature of Fatty Acids

Saturated fatty acids

Saturated FA have both trivial names and systematic names.

Usually saturated FA end as anoic acids.

 Nomenclature of Fatty Acids

Unsaturated fatty acids

They have trivial names, systematic names, ω-end

names and shorthand forms.

Usually Unsaturated FA end as enoic acids.

 Nomenclature of Fatty Acids

Unsaturated fatty acids

Representation of double bonds of FA 2 systems

2. ω-or n-
1. C-System
System
 1. C-System

18 17 16 15 14 13 12 11 10 9 8 1
CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH=CH-(CH2)7 -COOH

Oleic acid (C:18:1:∆9)

2. ω-or n-System

1 2 3 4 5 6 7 8 9 10 11 18
CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH=CH-(CH2)7 -COOH
Oleic acid (C:18:1:ω-9)
 FATTY ACIDS - CLASSIFICATION
Based on Length Based on Nature
Based on Total no
of hydrocarbon of hydrocarbon
of carbon atoms
chain chain
Short chain FA Saturated FA
Even chain FA
Medium chain FA Unsaturated FA

Long chain FA Branched chain FA

Odd chain FA
Very long chain FA Hydroxy FA
 Saturated fatty acids

• Saturated fatty acids belong to acetic acid series with general formula

CH3 (CH2 )n COOH

• Saturated fatty acids are either short-chained 2-10 carbons are liquid,

and Long-chained > 10 carbons are solid at 25 oC.

• The presence of double bonds in fatty acids significantly lowers the
melting point relative to a saturated fatty acid of the same length.
Cont..
• Some fatty acids are branched chains, e.g., phytanic acid, a
byproduct of chlorophyll catabolism in humans and animals
that could be secreted into milk and appear with butter. It is a
toxic compound if accumulated in the body due to failure of its
oxidation.
• Myristic acid functions as an anchor for plasma membrane
associating proteins.
• Human body fat contains 50% oleic acid, 25% palmitic acid,
10% linoleic and 5% stearic acid.
 SATURATED FATTY ACIDS
In which hydrocarbon side chain is saturated (no double bonds).
SATURATED FATTY ACIDS
 Unsaturated fatty acids
• Unsaturated fatty acids contain double bond and their systematic
names end in “enoic.”
• They are unstable and reactive due to the presence of the double
bond – therefore they are capable of taking up molecules of H2O,
H, I2, O2, B2 at each double bond
• Double bonds naturally occurring fatty acids are always in a cis-
form; However, In the body during metabolism trans fatty acids
are formed
• The presence of the double bond gives rise to the possibility of
geometric isomerism
 UNSATURATED FATTY ACIDS
In which hydrocarbon side chain is unsaturated.
One or more double bonds are present.

Subclassified according to number of double bonds

Monounsaturated FA Polyunsaturated FA

• One double bond • 2 or more double

bonds
 UNSATURATED FATTY ACIDS

Oleic acid (∆9 unsaturated stearic acid, C18:1∆9) is the most common fatty acid in natural
fats and is ω9.
UNSATURATED FATTY ACIDS
SATURATED & UNSATURATED FA
 Trans Fatty Acids (TFA)

 They are present in dairy products, high in processed foods and

bakery products and in hydrogenated edible oils. They are generally
considered to be injurious to health.
 However, they are used in food industry as they increase the shelf
life of the fried food.
 Oils containing PUFA (polyunsaturated fatty acids) also have high
content of TFA.
 Fast food preparations have a high TFA content.

 Trans fatty acids adversely affect multiple risk factors

 systemic inflammation, endothelial dysfunction, insulin resistance,
diabetes and adiposity.
 ESSENTIAL FATTY ACIDS
Polyunsaturated fatty acids, which are not synthesized in the body
and must be provided in the diet are called “essential fatty acids”
(EFA).
Lack of EFA in the diet can produce growth retardation and other
deficiency manifestation symptoms
They are - Linoleic acid (LA),
- Linolenic acid (LNA) and
- Arachidonic acid (AA).
Since plants and other organisms are capable of synthesizing PUFA,
humans can acquire these fats by consuming a variety of plants or else
by eating the meat of animals that have consumed these plant fats.
These essential fatty acids are also referred to as omega fatty acids.
 Why EFA cannot be Synthesized?
• Introduction of additional double bonds in unsaturated
fatty acid is limited to the area between – COOH group
and the existing double bond and that it is not possible
to introduce a double bond between the – CH3 group
at the opposite end of the molecule and the first
unsaturated linkage. This would explain body’s inability to
synthesise an EFA from oleic acid.
 Functions of EFA

1.Synthesis of Ecosanoids

2.Maintenance of structural integrity of

cells

3.Development of retina and brain

4.Antiatherogenic effect
 EFA function cont..
• Role in vision and in brain development: Docosahexaenoic polyenoic fatty acid
is formed from dietary linolenic acid. It is present in high concentrations in
retina, cerebral cortex, tastes and sperms
• It enhances the electrical response of the photoreceptors to illumination in
retinal membranes. Hence linolenic acid is necessary in the diet for optimal
vision.
• Structural element of mitochondrial membrane: A deficiency of EFA causes
swelling of mitochondrial membrane and reduction in efficiency of oxidative
phosphorylation. This may explain for increased heat production noted in EFA
deficient animals.
• Serum level of cholesterol: Fats with high content of
polyunsaturated fatty acids tends to lower serum level of cholesterol
 Which EFA is Important?

• Linoleic acid is most

important as,
arachidonic acid can be
synthesised from linoleic
acid

• Biologically arachidonic
acid is very important as
it is precursor from
which prostaglandins
and leukotrienes are
synthesised in the body.

Leukotrienes Prostaglandins
Thromboxanes
 EFA deficiency

Occurs if EFAs are excluded from diet for long period

The syndrome in humans characterized by

Horny eruptions on the posterior and lateral

parts of limbs, on the back and buttocks.
Phrynoderma Dermatitis
Poor wound healing
 Omega-3 Polyunsaturated Fatty Acids (PUFAs)
• There are three major types of omega-3 fatty acids that are
ingested in foods and used by the body

 α-Linolenic acid (ALA),

 eicosapentaenoic acid (EPA), and
 docosahexaenoic acid (DHA)
• Once eaten, the body converts ALA to EPA and DHA, the two
types of omega-3 fatty acids more readily used by the body
• It Serve as important precursors for lipid-derived modulators of
cell signaling, gene expression, and brain development.
Numerical Symbol Common Name and Structure Comments

Linoleic acid
18:2 Δ9,12
Omega-6 PUFA
Essential fatty acid

α-Linolenic acid (ALA)

18:3 Δ9,12,15
Omega-3 PUFA
Essential fatty acid

Arachidonic acid
20:4 Δ5,8,11,14
Omega-6 PUFA
Essential fatty acid

Eicosapentaenoic acid (EPA) Omega-3 PUFA

enriched in fish oils
20:5Δ5,8,11,14,17

Docosahexaenoic acid (DHA)

Omega-3 PUFA
22:6 Δ4,7,10,13,16,19
enriched in fish oils
 Omega-6 Polyunsaturated Fatty Acids (PUFAs)
• Most of the omega-6 PUFAs consumed in the diet are from vegetable oils and consist
of linoleic acid.
• Linoleic acid is converted to γ-linolenic acid (GLA) in the body.
• GLA is then then further converted to arachidonic acid
• The most important omega-6 PUFA is arachidonic acid.
• It is important in mediating inflammation
• When cells are stimulated by a variety of external stimuli, arachidonic acid is released
from cell membranes
• The released arachidonate then serves as the precursor for the synthesis of the
biologically active eicosanoids, the prostaglandins (PGs), thromboxanes (TXs), and
leukotrienes. (LTs)
• The arachidonate-derived eicosanoids function in diverse biological phenomena such
as platelet and leukocyte activation, signaling of pain, induction of
bronchoconstriction, and regulation of gastric secretions.