Chemistry of Lipids

Chemistry of Lipids
Definition
• Lipids are organic compounds formed mainly
from alcohol and fatty acids combined
together by ester linkage.

O
H2O O
R CH 2 OH
+ HO C R R CH 2 O C R
Fatty alcohol Fatty acid Esterase (lipase) ester (lipid)
Lipids are insoluble in water, but soluble
in fat or organic solvents (ether,
chloroform, benzene, acetone).
Lipids include fats, oils, waxes and
related compounds.
They are widely distributed in nature both
in plants and in animals.
 Biological Importance of Lipids:

1. They are more palatable and storable to unlimited amount

compared to carbohydrates.
2. They have a high-energy value (25% of body needs) and they
provide more energy per gram than carbohydrates and proteins
but carbohydrates are the preferable source of energy.
3. Supply the essential fatty acids that cannot be synthesized by
the body.
4. Supply the body with fat-soluble vitamins (A, D, E and K).
5. They are important constituents of the nervous system.
6. Tissue fat is an essential constituent of cell membrane and
nervous system. It is mainly phospholipids in nature that are
not affected by starvation.
7-Stored lipids “depot fat” is stored in all human cells acts as:
• A store of energy.
• A pad for the internal organs to protect them from outside
shocks.
• A subcutaneous thermal insulator against loss of body heat.
8-Lipoproteins, which are complex of lipids and proteins, are
important cellular constituents that present both in the cellular
and subcellular membranes.
9-Cholesterol enters in membrane structure and is used for
synthesis of adrenal cortical hormones, vitamin D3 and bile
acids.
10- Lipids provide bases for dealing with diseases such as obesity,
atherosclerosis, lipid-storage diseases, essential fatty acid
deficiency, respiratory distress syndrome,
 Classification of Lipids
 Simple lipids (Fats & Waxes)
 Compound or conjugated lipids
 Derived Lipids
 Lipid-associating substances
 Fatty alcohols
1-Glycerol:
• It is a trihydric alcohol (i.e., containing three
OH groups) and has the popular name
glycerin.
• It is synthesized in the body from glucose.
• It has the following properties:
1. Colorless viscous oily liquid with sweet taste.
2. On heating with sulfuric acid or KHSO4
(dehydration) it gives acrolein that has a bad
odor. This reaction is used for detection of
free glycerol or any compound containing
glycerol.

CH 2 OH 2 H 2O CHO

HO CH CH
Heating, KHSO4
CH 2 OH CH 2
Glycerol Acrolein
3-It combines with three molecules of nitric acid to form
trinitroglycerin (TNT) that is used as explosive and
vasodilator.
4-On esterification with fatty acids it gives:
• Monoglyceride or monoacyl-glycerol: one fatty acid
+ glycerol.
• Diglyceride or diacyl-glycerol: two fatty acids +
glycerol.
• Triglyceride or triacyl-glycerol: three fatty acids +
glycerol.
5-It has a nutritive value by conversion into glucose and
enters in structure of phospholipids.
Uses of Glycerol:
1. Glycerol enters in pharmaceutical and cosmetic
preparations.
2. Reduces brain edema in cerebrovascular disease.
3. Nitroglycerin is used as vasodilator especially for
the coronary arteries, thus it is used in treatment of
angina pectoris. Also, enters in explosives
manufacturing.
4. Glycerol is used in treatment of glaucoma
(increased intraocular pressure)due to its ability to
dehydrate the tissue from its water content.
 2-Sphingosine:
• - It is the alcohol(monohydric) present in
sphingolipids.
• - It is synthesized in the body from serine and
palmitic acid.
• It is not positive with acrolein test.
OH
CH 3 (CH 2 )12 CH CH CH CH NH 2

CH 2 OH
Sphingosine
 Fatty Acids
Definition:
• Fatty acids are aliphatic mono-carboxylic acids that
are mostly obtained from the hydrolysis of natural fats
and oils.
• Have the general formula R-(CH2)n-COOH and mostly
have straight chain (a few exceptions have branched
and heterocyclic chains). In this formula "n" is mostly
an even number of carbon atoms (2-34) with a few
exceptions that have an odd number.
• Fatty acids are classified according to several bases as
follows:
I. According to presence or absence of double
bonds they are classified into:
• A-Saturated Fatty Acids
• they contain no double bonds with 2-24 or
more carbons.
• They are solid at room temperature except if
they are short chained.
• They may be even or odd numbered.
• They have the following molecular formula,
CnH2n+1COOH.
Saturated fatty acids (no double )

A-Short chain Saturated F.A. (2-10 carbon).

a-Short chain Saturated volatile F.A.(2-6
carbon).
b- Short chain Saturated non volatile F.A.(7-10
carbon).
B-Long chain Saturated F.A.(more the10 carbon)
 a-Volatile short-chain fatty acids:
• They are liquid in nature and contain (1-6)
carbon atoms.
• water-soluble and volatile at room
temperature, e.g., acetic, butyric, and caproic
acids.
• Acetic F.A. (2C ) CH3-COOH.
• Butyric F.A. (4C ) CH3-(CH2)2-COOH.
• Caproic F.A. (6C ) CH3-(CH2)4-COOH.
b-Non-volatile short-chain fatty acids:
• They are solids at room temperature and
contain 7-10 carbon atoms.
• They are water-soluble and non-volatile at
room temperature include caprylic and capric
F.A.

• caprylic (8 C ) CH3-(CH2)6-COOH.
• Capric (10 C ) CH3-(CH2)8-COOH.
B-Long-chain fatty acids:
• They contain more than 10 carbon atoms.
• They occur in hydrogenated oils, animal fats, butter
and coconut and palm oils.
• They are non-volatile and water-insoluble
• Include palmitic, stearic, and lignoceric F.A.

• palmitic(16C) CH3-(CH2)14-COOH
• stearic (18 C ) CH3-(CH2)16-COOH
• lignoceric (24C ) CH3-(CH2)22-COOH
B-Unsaturated Fatty Acids
They contain double bond
• monounsaturated
they contain one double bonds .
(CnH2n-1 COOH)
• polyunsaturated
they contain more the one double bond (CnH2n-
more than 1 COOH).
1-Monounsaturated fatty acids:
1-Palmitoleic acid :
• It is found in all fats.
• It is C16:1∆9, i.e., has 16 carbons and one
double bond located at carbon number 9
and involving carbon 10.

CH3-( CH2 )5CH = CH-(CH2)7 –COOH

2-Oleic acid
• Is the most common fatty acid in natural fats.

• It is C18:1∆9, i.e., has 18 carbons and one

double bond located at carbon number 9 and
involving carbon 10.

CH3-(CH2)7- CH=CH – (CH2)7-COOH

3-Nervonic acid
(Unsaturated lignoceric acid).
• It is found in cerebrosides.
• It is C24:115, i.e., has 24 carbons and one
double bond located at carbon number 15
and involving carbon 16.

CH3 – (CH2)7 CH= CH – (CH2)13- COOH

2-Polyunsaturated fatty acids :
(Essential fatty acids):
• Definition:
• They are essential fatty acids that can not
be synthesized in the human body and must
be taken in adequate amounts in the diet.
• They are required for normal growth and
metabolism
• Source: vegetable oils such as corn oil,
linseed oil, peanut oil, olive oil, cottonseed
oil, soybean oil and many other plant oils,
cod liver oil and animal fats.
• Deficiency: Their deficiency in the diet leads
to nutrition deficiency disease.
• Its symptoms include: poor growth and
health with susceptibility to infections,
dermatitis, decreased capacity to reproduce,
impaired transport of lipids, fatty liver, and
lowered resistance to stress.
• Function of Essential Fatty Acids:
1. They are useful in the treatment of atherosclerosis by help
transporting blood cholesterol and lowering it and
transporting triglycerides.
2. The hormones are synthesized from them.
3. They enter in structure of all cellular and subcellular
membranes and the transporting plasma phospholipids.
4. They are essential for skin integrity, normal growth and
reproduction.
5. They have an important role in blood clotting (intrinsic
factor).
6. Important in preventing and treating fatty liver.
7. Important role in health of the retina and vision.
8. They can be oxidized for energy production.
1-Linoleic:
• C18:29, 12.
• It is the most important since other essential
fatty acids can be synthesized from it in the
body.

CH3-(CH2)4-CH = CH-CH2-CH=CH-(CH2)7-COOH
2-Linolenic acid:
• C18:39, 12, 15,
• in corn, linseed, peanut, olive, cottonseed
and soybean oils.

CH3-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-
(CH2)7-COOH
3-Arachidonic acid:
• C20:45, 8, 11, 14.
• It is an important component of
phospholipids in animal and in peanut oil
from which prostaglandins are synthesized.

CH3-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-
CH=CH-(CH2)3-COOH
 1-Simple Lipids
A-Neutral Fats and oils (Triglycerides)
Definition:
• - They are called neutral because they are
uncharged due to absence of ionizable groups
in it.
• The neutral fats are the most abundant lipids
in nature. They constitute about 98% of the
lipids of adipose tissue, 30% of plasma or liver
lipids, less than 10% of erythrocyte lipids.
• They are esters of glycerol with various fatty acids.
Since the 3 hydroxyl groups of glycerol are
esterified, the neutral fats are also called
“Triglycerides”.
• Esterification of glycerol with one molecule of fatty
acid gives monoglyceride, and that with 2 molecules
gives diglyceride.
O O
HO C R 1 CH 2 OH H 2C O C R1
O
O
HO C R 2 + HO C H R2 C O C H
O
O
CH 2 OH 3 H 2O H 2C O C R3
HO C R 3
Glycerol Triglycerides
Fatty acids (Triacylglycerol)
Types of triglycerides
1-Simple triglycerides: If the three fatty acids
connected to glycerol are of the same type the
triglyceride is called simple triglyceride, e.g.,
tripalmitin.
2-Mixed triglycerides: if they are of different types, it
is called mixed triglycerides, e.g., stearo-diolein and
palmito-oleo-stearin.
• Natural fats are mixtures of mixed triglycerides
with a small amount of simple triglycerides.
 O
CH 2 O C (CH 2 )14 CH 3
O
CH 3 (CH 2 )14 C O C H
O
CH 2 O C (CH 2 )14 CH 3
Tripalmitin
(simple triacylglycerol)
O
CH 2 O C (CH 2 )16 CH 3
O
CH 3 (CH 2 )7 CH CH (CH 2 )7 C O C H
O
CH 2 O C (CH 2 )7 CH CH (CH 2 )7 CH 3
1-Stearo-2,3-diolein
(mixed triacylglycerol)
O
CH 2 O C (CH 2 )14 CH 3
O
CH 3 (CH 2 )7 CH CH (CH 2 )7 C O C H
O
CH 2 O C (CH 2 )16 CH 3
1-palmito-2-oleo-3-stearin
(mixed triacylglycerol)
• The commonest fatty acids in animal
fats are palmitic, stearic and oleic acids.
• The main difference between fats and
oils is for oils being liquid at room
temperature, whereas, fats are solids.
• This is mainly due to presence of larger
percentage of unsaturated fatty acids in
oils than fats that has mostly saturated
fatty acids.
Physical properties of fat and oils:
1. Freshly prepared fats and oils are colorless,
odorless and tasteless.Any color, or taste is due to
association with other foreign substances, e.g.,
the yellow color of body fat or milk fat is due to
carotene pigments(cow milk).
2. Fats have specific gravity less than 1 and,
therefore, they float on water.
3. Fats are insoluble in water, but soluble in organic
solvents as ether and benzene.
4. Melting points of fats are usually low, but
higher than the solidification point,
Chemical Properties of fats and oils:
1-Hydrolysis:
• They are hydrolyzed into their constituents (fatty acids and
glycerol) by the action of super heated steam, acid, alkali or
enzyme (e.g., lipase of pancreas).
• - During their enzymatic and acid hydrolysis glycerol and free
fatty acids are produced.

O O
CH 2 O C R1 H 2C OH R1 C OH
O Lipase or Acid O
R2 C O C H HO C H + R C OH
2
O
O
CH 2 O C R3 3 H 2O H 2C OH
R3 C OH
Triacylglycerol Glycerol Free fatty acids
2-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
CH 2 O C R1 H 2C OH R1 C ON a
O O
R2 C O C H HO C H + R C ON a
2
O
O
CH 2 O C R3 3 NaOH H 2C OH
R3 C ON a
Triacylglycerol Glycerol Sodium salts of
fatty acids (soap)
3-Halogenation
• Neutral fats containing unsaturated fatty acids have the
ability of adding halogens (e.g., hydrogen or hydrogenation
and iodine or iodination) 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
4-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.
 Oils Hydrogen, high pressure, nickel Hard fat
(liquid) (margarine, solid)
(with unsaturated (with saturated
fatty acids, e.g., oleic) fatty acids, e.g., stearic)

Advantages for hydrogenated oil or fat are as follows:

1. It is more pleasant as cooking fat.
2. It is digestible and utilizable as normal animal fats and oils.
3. It is less liable to cause gastric or intestinal irritation.
4. It is easily stored and transported and less liable to
rancidity.
Disadvantages of hydrogenated
• fats include lack of fat-soluble vitamins (A, D, E and K) and
essential fatty acids
 B-Waxes
• Definition: Waxes are solid simple lipids containing
a monohydric alcohol (with a higher molecular
weight than glycerol) esterified to long-chain fatty
acids. Examples of these alcohols are palmitoyl
alcohol, cholesterol, vitamin A or D.
• Properties of waxes: Waxes are insoluble in water,
but soluble in fat solvents and are negative for
acrolein test.
• Waxes are not easily hydrolyzed as the fats and are
indigestible by lipases and are very resistant to
rancidity.
• Thus they are of no nutritional value.
 Type of Waxes:
• - Waxes are widely distributed in nature such as the
secretion of certain insects as bees-wax, protective
coatings of the skins and furs of animals and leaves
and fruits of plants. They are classified into true-
waxes and wax-like compounds as follows:
A-True waxes: include:
• Bees-wax is secreted by the honeybees that use it to
form the combs. It is a mixture of waxes with the
chief constituent is mericyl palmitate.
 O O
C 15 H 31 C OH + C 30 H 61 OH C 15 H 31 C O C 30 H 61

Palmitic Mericyl Mericyl

H2O
acid alcohol palmitate

B-Wax-like compounds:
• Cholesterol esters: Lanolin (or wool fat) is
prepared from the wool-associated skin glands
and is secreted by sebaceous glands of the skin.
• It is very complex mixture, contains both free and
esterified cholesterol, e.g., cholesterol-palmitate
and other sterols.
Differences between neutral lipids and waxes:

Waxes Neutral lipids

1.Digestibility: Indigestible (not Digestible (hydrolyzed by lipase).

hydrolyzed by lipase).

2-Type of Long-chain monohydric Glycerol (trihydric) + 3 fatty acids

alcohol: alcohol + one fatty acid.

3-Type of fatty Fatty acid mainly palmitic Long and short chain fatty acids.
acids: or stearic acid.

4-Acrolein test: Negative. Positive.

5-Rancidability: Never get rancid. Rancidible.

6-Nature at Hard solid. Soft solid or liquid.

room
temperature.
7-Saponification Nonsaponifiable. Saponifiable.

8-Nutritive No nutritive value. Nutritive.

value:
9-Example: Bee & carnuba waxes. Butter and vegetable oils.
 2-Compound Lipids
Definition:
• They are lipids that contain additional substances,
e.g., sulfur, phosphorus, amino group,
carbohydrate, or proteins beside fatty acid and
alcohol.
• Compound or conjugated lipids are classified into
the following types according to the nature of the
additional group:
1. Phospholipids
2. Glycolipids.
3. Lipoproteins
4. Sulfolipids and amino lipids.
 A-Phospholipids
Definition: Phospholipids or phosphatides are compound lipids,
which contain phosphoric acid group in their structure.
Importance:
1. They are present in large amounts in the liver and brain as
well as blood. Every animal and plant cell contains
phospholipids.
2. The membranes bounding cells and subcellular organelles
are composed mainly of phospholipids. Thus, the transfer of
substances through these membranes is controlled by
properties of phospholipids.
3. They are important components of the lipoprotein coat
essential for secretion and transport of plasma lipoprotein
complexes. Thus, they are lipotropic agents that prevent
fatty liver.
4. Myelin sheath of nerves is rich with phospholipids.
5-Important in digestion and absorption of neutral
lipids and excretion of cholesterol in the bile.
6-Important function in blood clotting and platelet
aggregation.
7-They provide lung alveoli with surfactants that
prevent its irreversible collapse.
8-Important role in signal transduction across the cell
membrane.
9-Phospholipase A2 in snake venom hydrolyses
membrane phospholipids into hemolytic
lysolecithin or lysocephalin.
10-They are source of polyunsaturated fatty acids for
synthesis of eicosanoids.
Sources: They are found in all cells (plant and
animal), milk and egg-yolk in the form of
lecithins.
Structure: phospholipids are composed of:
1. Fatty acids (a saturated and an unsaturated
fatty acid).
2. Nitrogenous base (choline, serine,
threonine, or ethanolamine).
3. Phosphoric acid.
4. Fatty alcohols (glycerol, inositol or
sphingosine).
• Classification of Phospholipids are classified
into 2 groups according to the type of the alcohol
present into two types:
A-Glycerophospholipids: They are regarded as derivatives
of phosphatidic acids that are the simplest type of
phospholipids and include:
1. Phosphatidic acids.
2. Lecithins
3. Cephalins.
4. Plasmalogens.
5. Inositides.
6. Cardiolipin.
B-Sphingophospholipids: They contain sphingosine as an
alcohol and are named Sphingomyelins.
A-Glycerophospholipids
1-Phosphatidic acids:They are metabolic intermediates in
synthesis of triglycerides and glycerophospholipids in the
body and may have function as a second messenger. They
exist in two forms according to the position of the
phosphate
O
Saturated
 CH2 O C R1
Polyunsaturated O fatty acid

fatty acid R2 C O C H
O
 CH2 O P OH Phosphate
OH
-Phosphatidic acid
O
 C H2 Saturated
O C R1
O fatty acid

Phosphate H O P O C H
OH O
Polyunsaturated
 C H2 O C R2
fatty acid
 -Phosphatidic acid
2-Lecithins:
• Definition: Lecithins are glycerophospholipids that
contain choline as a base beside phosphatidic acid.
They exist in 2 forms - and -lecithins. Lecithins are
a common cell constituent obtained from brain (-
type), egg yolk (-type), or liver (both types).
Lecithins are important in the metabolism of fat by
the liver.
• Structure: Glycerol is connected at C2 or C3 with a
polyunsaturated fatty acid, at C1 with a saturated
fatty acid, at C3 or C2 by phosphate to which the
choline base is connected. The common fatty acids in
lecithins are stearic, palmitic, oleic, linoleic, linolenic,
clupandonic or arachidonic acids.
Lysolecithin causes hemolysis of RBCs. This partially explains
toxic the effect of snake venom,. The venom contains
lecithinase, which hydrolyzes the polyunsaturated fatty
converting lecithin into lysolecithin. Lysolecithins are
intermediates in metabolism of phospholipids.

O
CH2 O C R1
O
R2 C O C H
O CH3
CH2 O P O CH2 CH2 N
+ C H3
OH Choline C H3
-Lecithin
O
C H2 O C R1
CH3 O
CH3
+N CH2 C H2 O P O C H
OH O
CH3 Choline
C H2 O C R2
 -Lecithin
• Lung surfactant
• Is a complex of dipalmitoyl-lecithin, sphingomyelin and a
group of apoproteins called apoprotein A, B, C, and D.
• It is produced by type II alveolar cells and is anchored to
the alveolar surface of type II and I cells.
• It lowers alveolar surface tension and improves gas
exchange besides activating macrophages to kill
pathogens.
• In premature babies, this surfactant is deficient and they
suffer from respiratory distress syndrome.
• Glucocorticoids increase the synthesis of the surfactant
complex and promote differentiation of lung cells.
3-Cephalins (or Kephalins):
• Definition: They are phosphatidyl-
ethanolamine or serine. Cephalins occur in
association with lecithins in tissues and are
isolated from the brain (Kephale = head).
• Structure: Cephalins resemble lecithins in
structure except that choline is replaced by
ethanolamine, serine or threonine amino
acids.
• Certain cephalins are constituents of the complex mixture of
phospholipids, cholesterol and fat that constitute the lipid
component of the lipoprotein “thromboplastin” which
accelerates the clotting of blood by activation of
prothrombin to thrombin in presence of calcium ions.

O
CH 2 O C R1
O
R2 C O C H
O
CH 2 O P O CH 2 CH 2 NH 2 Ethanolamine
OH H O CH 2 CH COO H Serine
-Cephalin
NH 2
HO CH CH COO H Threonine
CH 3 NH 2
4-Plasmalogens:
• Definition: Plasmalogens are found in the cell
membrane phospholipids fraction of brain and
muscle (10% of it is plasmalogens), liver, semen and
eggs.
• Structure: Plasmalogens resemble lecithins and
cephalins in structure but differ in the presence of
,-unsaturated fatty alcohol rather than a fatty
acid at C1 of the glycerol connected by ether bond.
• At C2 there is an unsaturated long-chain fatty acid,
however, it may be a very short-chain fatty acid
• Properties: Similar to lecithins.

-Unsaturated
CH 2 O CH CH R 1 fatty alcohol
O
R2 C O C H
O CH 3
CH 2 O P O CH 2 CH 2 N CH 3
+
OH CH 3
-Plasmalogen
5-Inositides:
• Definition:
• - They are phosphatidyl inositol.
• Structure: They are similar to lecithins or cephalins but they
have the cyclic sugar alcohol, inositol as the base. They are
formed of glycerol, one saturated fatty acid, one unsaturated
fatty acid, phosphoric acid and inositol
O
CH 2 O C R1
O
R2 C O C H
O OH OH
2 3
CH 2 O P O H H H
1 OH 4
OH H
H OH
6 5
-Phosphatidylinositol OH H
• Source: Brain tissues.
• Function:
• Phosphatidyl inositol is a major component of cell
membrane phospholipids particularly at the inner
leaflet of it.
• They play a major role as second messengers
during signal transduction for certain hormone..
• On hydrolysis by phospholipase C, phosphatidyl-
inositol-4,5-diphosphate produces diacyl-glycerol
and inositol-triphosphate both act to liberate
calcium from its intracellular stores to mediate the
hormone effects.
6-Cardiolipins:
• Definition: They are diphosphatidyl-glycerol. They are found
in the inner membrane of mitochondria initially isolated
from heart muscle (cardio). It is formed of 3 molecules of
glycerol, 4 fatty acids and 2 phosphate groups.
• Function: Used in serological diagnosis of autoimmunity
diseases.

O OH
CH 2 O C R1 CH 2 O P O CH 2
O
O
R2 C O C H H C OH H C O C R3
O
O
CH 2 O P O CH 2 R 4 C O CH 2
OH O
Cardiolipin
B-Sphingophospholipids
1-Sphingomyelins
• Definition: Sphingomyelins are found in large amounts in
brain and nerves and in smaller amounts in lung, spleen,
kidney, liver and blood.

• Structure: Sphingomyelins differ from lecithins and cephalins

in that they contain sphingosine as the alcohol instead of
glycerol, they contain two nitrogenous bases: sphingosine
itself and choline.
• Thus, sphingomyelins contain sphingosine base, one long-
chain fatty acid, choline and phosphoric acid.
• To the amino group of sphingosine the fatty acid is attached
by an amide linkage.
• Ceramide This part of sphingomyelin in which the amino
group of sphingosine is attached to the fatty acid by an
amide linkage.
• Ceramides have been found in the free state in the spleen,
liver and red cells.
Ceramide

Sphingosine
Fatty acid
OH O
CH 3 (CH 2 )12 CH CH CH CH NH C R1

CH 2 Choline
O CH 3
O P O CH 2 CH 2 N
+ CH 3
OH CH 3
Phosphate
Sphingomyelin
 B-Glycolipids
• Definition: They are lipids that contain carbohydrate
residues with sphingosine as the alcohol and a very long-
chain fatty acid (24 carbon series).
• They are present in cerebral tissue, therefore are called
cerebrosides
• Classification: According to the number and nature of
the carbohydrate residue(s) present in the glycolipids the
following are
1. Cerebrosides. They have one galactose molecule
(galactosides).
2. Sulfatides. They are cerebrosides with sulfate on the
sugar (sulfated cerebrosides).
3. Gangliosides. They have several sugar and sugaramine
residues.
1-Cerebrosides:
• Occurrence: They occur in myelin sheath of nerves and white matter of the
brain tissues and cellular membranes. They are important for nerve
conductance.
• Structure: They contain sugar, usually -galactose and may be glucose or
lactose, sphingosine and fatty acid, but no phosphoric acid.
Ceramide

Sphingosine
Fatty acid
OH O
CH 3 (CH 2 )12 CH CH CH CH NH C R1

CH 2

CH 2 OH O
OH O
H
Galactose
OH H
H H

H OH

Psychosin
Cerebroside
• Types: According to the type of fatty acid and
carbohydrate present, there are 4 different types
of cerebrosides isolated from the white matter of
cerebrum and in myelin sheaths of nerves. Rabbit
cerebrosides contain stearic acid.
1. Kerasin contains lignoceric acid (24 carbons) and
galactose.
2. Cerebron (Phrenosin) contains cerebronic acid (2-
hydroxylignoceric acid) and galactose.
3. Nervon contains nervonic acid (unsaturated
lignoceric acid at C15) and galactose.
4. Oxynervon contains oxynervonic acid (2-
hydroxynervonic acid) and galactose.
2-Sulfatides:
• They are sulfate esters of kerasin or phrenosin in which the
sulfate group is usually attached to the –OH group of C3 or
C6 of galactose. Sulfatides are usually present in the brain,
liver, muscles and testes.

OH O
CH 3 (CH 2 )12 CH 2 CH CH CH NH C R1

CH 2

CH 2 OH
O O
OH
H
OS O 3 H H
H H
H OH
Sulfatides (sulfated cerebroside)
3-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.
• Gangliosides contain sialic acid (N-acetylneuraminic acid),
ceramide (sphingosine + fatty acid of 18-24 carbon atom
length), 3 molecules of hexoses (1 glucose + 2 galactose) and
hexosamine. The most simple type of it the
monosialoganglioside,. It works as a receptor for cholera
toxin in the human intestine.

Ceramide-Glucose-Galactose-N-acetylgalactosamine-Galactose
Sialic acid
Monosialoganglioside
 C-Lipoproteins
• Definition: Lipoproteins are lipids combined with proteins in
the tissues. The lipid component is phospholipid,
cholesterol or triglycerides. The holding bonds are
secondary bonds.
• They include:
1. Structural lipoproteins: These are widely distributed in
tissues being present in cellular and subcellular membranes.
In lung tissues acting as a surfactant in a complex of a
protein and lecithin. In the eye, rhodopsin of rods is a
lipoprotein complex.
• Transport lipoproteins:
• These are the forms present in blood plasma. They are
composed of a protein called apolipoprotein and different
types of lipids. (Cholesterol, cholesterol esters,
phospholipids and triglycerides). As the lipid content
increases, the density of plasma lipoproteins decreases
• Plasma lipoproteins can be separated by two methods:
1. Ultra-centrifugation: Using the rate of floatation in sodium
chloride solution leading to their sequential separation into
chylomicrons, very low density lipoproteins (VLDL or pre--
lipoproteins), low density lipoproteins (LDL or -
lipoproteins), high density lipoproteins (HDL or -
lipoproteins) and albumin-free fatty acids complex.
2. Electrophoresis: is the migration of charged particles in an
electric field either to the anode or to the cathode. It
sequentially separates the lipoproteins into chylomicrons,
pre--, -, and -lipoprotein and albumin-free fatty acids
complex.

Polar lipids
(phospholipids)
Polar apolipoproteins
Nonpolar lipids
(cholesterol and its esters
and triacylglycerols)
Structure of a plasma lipoprotein complex
a) Chylomicrons: They have the largest diameter and the
least density. They contain 1-2% protein only and 98-99% fat.
The main lipid fraction is triglycerides absorbed from the
intestine and they contain small amounts of the absorbed
cholesterol and phospholipids.
b) Very low-density lipoproteins (VLDL) or pre--
lipoproteins: Their diameter is smaller than chylomicrons.
They contain about 7-10% protein and 90-93% lipid. The lipid
content is mainly triglycerides formed in the liver. They
contain phospholipid and cholesterol more than
chylomicrons.
c) Low-density lipoproteins (LDL) or -lipoproteins:
They contain 10-20% proteins in the form of apolipoprotein
B. Their lipid content varies from 80-90%. They contain
about 60% of total blood cholesterol and 40% of total blood
phospholipids. As their percentage increases, the liability to
atherosclerosis increases.
d) High-density lipoproteins (HDL) or -Lipoproteins:
They contain 35-55% proteins in the form of
apolipoprotein A. They contain 45-65% lipids
formed of cholesterol (40% of total blood content)
and phospholipids (60% of total blood content).
They act as cholesterol scavengers, as their
percentage increases, the liability to atherosclerosis
decreases. They are higher in females than in males.
Due to their high protein content they possess the
highest density.
e) Albumin-free fatty acids complex: It is a proteolipid
complex with 99% protein content associated with
long-chain free fatty acids for transporting them.
Cholesterol:
• Importance: -
• 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).
• Steroid hormones, bile salts and vitamin D are derivatives
from it.
• Tissues contain different amounts of it that serve a
structural and metabolic role, e.g., adrenal cortex content is
10%, whereas, brain is 2%, others 0.2-0.3%.
• Source: - It is synthesized in the body from acetyl-CoA
(1gm/day, cholesterol does not exist in plants) and is also
taken in the diet (0.3 gm/day as in, butter, milk, egg yolk,
brain, meat and animal fat).
Physical propeties:It has a hydroxyl group on C3, a double
bond between C5 and C6, 8 asymmetric carbon atoms and a
side chain of 8 carbon atoms.
• It is found in all animal cells, corpus luteum and adrenal
cortex, human brain (17% of the solids).
• In the blood (the total cholesterol amounts about 200 mg/dL
of which 2/3 is esterified, chiefly to unsaturated fatty acids
while the remainder occurs as the free cholesterol.

CH 3
CH 3
CH 3
CH 3
CH 3

HO
Cholesterol
• Chemical properties Intestinal bacteria reduce
cholesterol into coprosterol and dihydrocholesterol.
• - It is also oxidized into 7-Dehydrocholesterol and further
unsaturated cholesterol with a second double bond between
C7 and C8. When the skin is irradiated with ultraviolet light
7-dehydrocholesterol is converted to vitamin D3. This
explains the value of sun light in preventing rickets.

CH 3 CH 3
CH 3 CH 3
CH 3 CH 3
CH 3 CH 3
CH 3 CH 3

HO HO
H H
Coprosterol, Dihydrocholesterol,
in feces in blood and other tissues
• Ergosterol differs from 7-dehydrocholesterol in the side
chain. Ergosterol is converted to vitamin D2 by irradiation
with UV Ergosterol and 7- dehydrocholesterol are called Pro-
vitamins D or precursors of vitamin D.
• - It was first isolated from ergot, a fungus then from yeast.
Ergosterol is less stable than cholesterol (because of having 3
double bonds).

CH 3 CH 3
CH 3 CH 3
CH 3 CH 3
CH 3 CH 3 CH 3
CH 3 CH 3

HO HO
7-dehydrocholesterol Ergosterol
 Steroids
• Steroids constitute an important class of biological
compounds.
• Steroids are usually found in association with fat.
They can be separated from fats after
saponification since they occur in the
unsaponifiable residue.
• They are derivatives of cholesterol that is formed
of steroid ring or nucleus.
• Biologically important groups of substances, which contain
this ring, are:
1. Sterols.
2. Adrenal cortical hormones.
3. Male and female sex hormones.
4. Vitamin D group.
5. Bile acids.
6. Cardiac glycosides.
• General consideration about naturally occurring steroids:
A typical member of this group is cholesterol. Certain facts have to be
considered when drawing steroid formula:
1) There is always oxygen in the form of hydroxyl or ketone on C3.
2) Rings C and D are saturated (stable).
3) Methyl groups at C18 C19. In case of vitamin D, the CH3 group at C19
becomes a methylene group (=CH2) and the ring B is opened, whereas,
this methyl group is absent in female sex hormones (estrogens).
4) In estrogens (female sex hormones) ring A is aromatic and there is no
methyl group on C10.

18
12 CH 3
16
19 11 13 17
CH 3 C D
1 9 14 15
2
A 5 10 B 8
HO 3 4 6 7
Steroid ring
• Bile acids:
• They are produced from oxidation of cholesterol in the liver
producing cholic and chenodeoxycholic acids that are
conjugated with glycine or taurine to produce glycocholic,
glycochenodeoxycholic, taurocholic and
taurochenodeoxycholic acids. They react with sodium or
potassium to produce sodium or potassium bile salts.
• Their function is as follows:
1. Emulsification of lipids during digestion.
2. Help in digestion of the other foodstuffs.
3. Activation of pancreatic lipase.
4. Help digestion and absorption of fat-soluble vitamins.
5. Solubilizing cholesterol in bile and prevent gall stone
formation.
6. Choleretic action (stimulate their own secretion).
7. Intestinal antiseptic that prevent putrefaction
 CH 3 CH 3
OH CH CH 3
3 C R 1 or R 2 C R 1 or R 2

CH 3 O O
CH 3

HO OH HO OH
Sodium-tauro or Sodium-tauro or
glyco-cholate glyco-chenodeoxycholate
R1 H 2N CH 2 COO -Na + R2 H 2N (CH 2)2 SO 3-Na +
Sodium glycate Sodium taurate
Fatty Acid Synthesis
 Fatty Acid Synthesis Occurs in the
Cytosol
• Must have source of acetyl-CoA
• Most acetyl-CoA in mitochondria
• Citrate-malate-pyruvate shuttle provides cytosolic acetate units and reducing
equivalents for fatty acid synthesis

Citrate Lyase
Citrate synthase

Malate
dehydrogenase
Pyruvate
carboxylase Malate Enzyme
 Fatty Acid Synthesis
• Fatty acids are built from 2-C units derived from
acetyl-CoA
• Acetate units are activated for transfer to growing FA
chain by conversion to malonyl-CoA
• Decarboxylation of malonyl-CoA and reducing power
of NADPH drive chain growth
• Chain grows to 16-carbons (eight acetyl-CoAs)
• Other enzymes add double bonds and more carbons
 Fatty Acid Synthesis
• Step 1: Loading – transferring acetyl- and malonyl- groups
from CoA to ACP (Acetyl Carrier Protein - ACP),
• Step 2: Condensation – transferring 2 carbon unit from
malonyl-ACP to acetyl-ACP to form 2 carbon keto-acyl-ACP
• Step 3: Reduction – conversion of keto-acyl-ACP to
hydroxyacyl-ACP (uses NADPH)
• Step 4: Dehydration – Elimination of H2O to form Enoyl-
ACP
• Step 5: Reduction – Reduce double bond to form 4 carbon
fully saturated acyl-ACP
 Step 1: Loading Reactions

O H O
O
H3C C S CoA C C C S CoA
acetyl-CoA
O malonyl-CoA
HS-ACP H HS-ACP
acetyl-CoA:ACP
transacylase MAT malonyl-CoA:ACP
transacylase
HS-CoA HS-CoA

O H O
O
H3C C S ACP C C C S ACP
O malonyl-ACP
acetyl-ACP H
 Step 2: Condensation Rxn
O
H3C C S ACP
acetyl-ACP
HS-Ketoacyl-ACP Synthase
-ketoacyl-ACP synthase (KS)

HS-ACP

H O O
O
C C C S ACP + H3C C S ketoacyl-ACP Synthase
O malonyl-ACP
H

keto-ACP synthase
CO2

O H O
H3C C C C S ACP
H acetoacetyl-ACP
 Step 3: Reduction

O H O
H3C C C C S ACP
H acetoacetyl-ACP
KR NADPH + H
+

Ketoacyl-ACP Reductase

+
NADP

OH H O
H3C C C C S ACP
H -hydroxybutyryl-ACP
H
Step 4: Dehydration

OH H O
H3C C C C S ACP
H -hydroxyacyl-ACP
H
DH
-hydroxyacyl-ACP
dehydrase
H20

H O
H3C C C C S ACP
trans-enoyl-ACP
H
Step 5: Reduction

H O
H3C C C C S ACP
trans-enoyl-ACP
H
ER NADPH + H+

enoyl-ACP reductase

NADP+

H H O
H3C C C C S ACP
H trans-enoyl-ACP
H
 Step 6: next condensation
H H O
H3C C C C S ACP
butyryl-ACP
H H
HS-Ketoacyl-ACP Synthase
KS
HS-ACP

H O H H O
O
C C C S ACP + H3C C C C S KAS
O malonyl-ACP H H
H

keto-ACP synthase
CO2

H H O H O
H3C C C C C C S ACP
H ketoacyl-ACP
H H
 H O
H3C C C S ACP Palmitoyl-ACP

Termination of H
14

Fatty Acid Synthesis

Thioesterase
HS-ACP

H O
H3C C C O Palmitic Acid

H
14
ATP + HS-CoA
Acyl-CoA
synthetase

AMP + PPi

H O
H3C C C S CoA
Palmitoyl-CoA
H
14
 Acetyl Coenzyme A
• Acetyl Coenzyme A is the starting material for fatty
acid biosynthesis.
• It is derived from metabolism of carbohydrates, fats
and some amino acids.
• The two-carbon piece provides the carbons for the
new fatty acid.
O
H3C C S CoA Acetyl Coenzyme A

89
Step 1: Preparation of Malonyl CoA
O AT P AD P + P i
O
-

O O
O C + H3C C S CoA O
-

C CH2 C S CoA
OH Acetyl C oA M alonyl C oA

• Acetyl CoA reacts with bicarbonate to form

Malonyl CoA.
• This is energy-requiring, so hydrolysis of an
ATP is used to drive the reaction.
• Malonyl CoA is more reactive than Acetyl CoA.
90
 Step 2: Transthioesterifaction
O O
HS ACP
H3C C S CoA H3C C S ACP + HS CoA
Acetyl C oA Acetyl AC P

O O O O
HS ACP
O-

C CH2 C S CoA O -

C CH2 C S ACP
M alonyl C oA M alonyl AC P + HS CoA

• Both Acetyl CoA and Malonyl CoA are connected to Acetyl

Carrier Protein (ACP), which is another thiol.
• One thiol replaces another to make a different thioester.
• ACP shuttles the molecules to the different enzymes needed
to do the following reactions.
91
Transport of acetyl CoA from the mitochondrial matrix into the cytosol
 Fatty acid biosynthesis
1. Acetyl-CoA is converted by MAT to
Acetyl ACP
2. Acetyl-ACP is attached to KS
(condensation reaction).
3. Malonyl ACP is formed by MAT.
4. Acetyl-group is coupled to beta carbon
of malonyl-ACP with release of CO2 to
form acetoacetyl-ACP(2b) by KS.
5. Reduction of acetoacetyl-ACP with
NADPH to form D--hydroxybutyrl-ACP
by DH
6. Dehydration of D--hydroxybutyrl-ACP
by ER to form a,b-trans-butenoyl-ACP
7. Reduction of the double bond to form
Page 933

butyryl-ACP
8. Repeat until Palmitoyl-ACP (C16) is
formed.
9. ACP is cleaved by TE releasing free fatty
acid.
3. The elongation cycle of fatty acid synthesis has four
stages for each round of synthesis

Condensation
Reduction
Dehydration
Reduction
Further processing of C16 fatty acids
Unsaturated fatty acid synthesis

Desaturase
Synthesis of triacylglycerols
 Pi
Triacylglycerol Diacylglycerol
Cholesterol

Cholesterol biosynthesis

Acetyl-CoA MVA IPP Squalene

Lanosterol Cholesterol
Acetyl-CoA

Mevalonate
Mevalonate

IPP

Squalene
Squalene

Lanosterol

Cholesterol
Biosynthesis of bile acids
Steroid hormones
 Lipid metabolism
• Triacylglycerol (fats and oils) are an efficient
form for storage of reduced carbon,
particularly in seeds. Polar glycerolipids are
the primary structural components of
membranes.
• Triacylglycerols are synthesized in the ER and
accumulate within the phospholipid bilayer,
forming oil bodies.
Cycle of fatty acid synthesis in plastids of plant cells
ACP: acyl carrier protein

108
Figure 11.17 The two pathways for glycerolipid synthesis

109
• Fatty acids are synthesized in plastids using acetyl-
CoA, in cycles of two-carbon addition. Fatty acids
from the plastids can be transported to the ER,
where they are further modified.
• The function of a membrane may be influenced by its
lipid composition. The degree of unsaturation of the
fatty acids influences the sensitivity of plants to cold,
but does not seem to be involved in normal chiling
injury.
• Certain membrane lipid breakdown products, such as
jasmonic acid, can act as signaling agents in plant
cells

110
Conversion of fats into sugars; (A) Carbon flow during fatty acid breakdown

111
 Germination
• During germination in oil-storing seeds, the
stored lipids are metabolized to carbohydrates
in a series of reactions that include the
glyoxylate cycle. The glyoxylate cycle takes
place in glyoxysomes, and subsequent steps
occur in mitochondria.
• The reduced carbon generated during lipid
breakdown in the glyoxysomes is ultimately
converted into carbohydrates in the cytosol by
gluconeogenesis.

112
 ß-Oxidation

 To generate energy, lipid from storage will first hydrolyzed by lipase enzyme
 The free fatty acids will be catabolized through beta-oxidation in mitochondrial

matrix in the case of mammals and in glyoxysome in plants

 For ß-Oxidation, fatty acid must first cross the outer membrane of mitochondrion
 This requires activation of fatty acid
 Fatty acids are activated by enzymes (acyl-CoA synthetases) in the outer

mitochondrial membrane
 These enzymes catalyze the formation of a thioester linkage between the fatty acid

and coenzyme A (CoA-SH) to form fatty acyl-CoA

 This reaction is coupled to the cleavage of ATP to AMP and PPi
Activation of Fatty Acids

Fatty acy-CoA
Fatty acid
 The fatty acyl-CoA corsses the inner membrane of mitochondria
through the assistance of carrier compound, carnitine
 The fatty acyl-carnitine ester, formed by the action of carnitine
acyltransferase I, is carried into the matrix by facillitated difusion via
acyl-carnitine/carnitine transporter

 In the matrix, ß-Oxidation occurs. This involves oxidation of the fatty

acid at the ß-carbon (C-3) , followed by hydration, an oxidation and
thiolysis
 This is a series of reactions that results in the removal of C-1 and C-2
as a molecule of acetyl-CoA
Beta Oxidation
Beta Oxidation
Beta Oxidation
Beta Oxidation
 Fatty acids provide highly efficient energy storage, storing much
more energy for their weight than carbohydrates like glucose.
 Fatty acids are stored as triglycerides in adipose tissue, in which each
triglyceride molecule contains three fatty acids and one glycerol.
 Triglycerides form fatty droplets that exclude water and take up
minimal space.
 Fatty acids are also more highly reduced than carbohydrates, so they
provide more energy during oxidation.
 The efficiency of energy storage in fats is probably an important
reason why animals store most of their energy as fats and only a
small amount of energy as carbohydrates
 When glucose levels are low during long periods between
meals the enzyme glucagon secreted by the pancreas stimulates
adipose lipase activity to release fatty acids from triglycerides.
 Once released, these fatty acids travel through the blood to
other tissues such as muscle where they are oxidized to provide
energy through the mitochondrial beta-oxidation pathway.
 Since fatty acid beta-oxidation occurs in the mitochondrial
matrix, long-chain fatty acids must be actively transported
from the cytoplasm into mitochondria by carnitine palmitoyl
transferase
 The chemical energy contained in fatty acids is released through the beta-
oxidation of fatty acids in mitochondria.
 The beta-oxidation pathway includes four reactions that occur in repeating cycles
with each fatty acid molecule.
 In each cycle, a fatty acid is progressively shortened by two carbons as it is
oxidized and its energy captured by the reduced energy carriers NADH and
FADH2.
 At the end of each cycle of four reactions, one acetyl-CoA two-carbon unit is
released from the end of the fatty acid, which then goes through another round of
beta-oxidation, continuing to oxidize and shorten even-chain fatty acids until they
are entirely converted to acetyl-CoA.
 Fatty acids with an odd number of carbons in the acyl chain are left at the end
with propionyl-CoA, with 3 carbons, which cannot enter another round of beta-
oxidation.
 The propionyl-CoA produced in this manner is converted to
succinyl-CoA that then enters the Krebs cycle
 The acetyl-CoA generated in beta-oxidation enters the Krebs cycle,
where it is further oxidized to CO2, producing more reduced energy
carriers, NADH and FADH2
 These carriers produced in the Krebs cycle, along with those
produced directly in beta-oxidation, transfer their energy to the
electron transport chain where they drive the creation of the proton
gradient that supports mitochondrial ATP production.
Lipid Biosynthesis