Lipid

Structure and Metabolism

I.

Introduction and Classification

II.

Nomenclature and Structure

III.

Biological Membrane

IV.

Metabolism
A.

Oxidation of Fatty Acids

B.

Ketone Body Formation

C.

Biosynthesis of Fatty Acids

D.

Lipogenesis and Lipolysis

Introduction
Biological molecules that are insoluble in aqueous solutions and soluble
in organic solvents, have some relation to fatty acids as esters, and have
potentiality of utilization by living organisms are classified as lipids.

They perform four major physiological functions:

1.

Serve as structural components of biological membranes

2.

Provide energy reserves, predominantly in the form of

triacylglycerols

3.

Both lipids and lipid derivatives serve as vitamins and

hormones

4.

Lipophilic bile acids aid(membantu) in lipid solubilization

Classification
Bloors Classification
A.

Simple lipid - ester of fatty acids with various alcohols

1.

Natural fats and oils (triglycerides)

2.

Waxes
(a) True waxes: cetyl alcohol esters of fatty acids
(b) Cholesterol esters

CH3

CH3

(c) Vitamin A esters

(d) Vitamin D esters
B.

CH3
E

OH
CH3
CH3

Compound lipid - esters of fatty acids with alcohol plus other

groups
1. Phospholipids and spingomyelin: contains phosphoric
acid and often a nitrogenous base
2.

Spingolipids (also include glycolipids and cerebrosides):

contains aminoalcohol spingosine, carbohydrate, N-base;
glycolipids contains no phosphate

3.

Sulfolipids : contains sulfate group

4.

Lipoproteins : lipids attached to plasma/other proteins

5.

Lipopolysaccharides: lipids attached to polysaccharides

Classification cont.
C.

Derived lipids hydrolytic products of A & B with lipid

characters
1.

Saturated & unsaturated fatty acids

2.

Monoglycerides and diglycerides

3. Alcohols (-carotenoid ring, e.g., vitamin A,

carotenoids)
D.

certain

Miscellaneous lipids
1. Aliphatic hydrocarbons: found in liver fat and certain
hydrocarbon found in beeswax and plant waxes
2.

Carotenoids

3.

Squalene : found in shark and mammalian liver and in

human sebam; an important intermediate in biosynthesis
of cholesterol

4.

Vitamin E and K

Figure 43

Nomenclature and Structure

Fats and oils:
Vegetable oils are triglycerides that are liquid at room
temp
due to their higher unsaturated or shorter-chain fatty
acids
Triglycerides are most abundant natural lipids

Natural fats have D-configuration

Usually R1 and R3 are saturated and R2 is unsaturated
Natural fats are mixture of two or more simple triglycerides

Fatty acids
A fatty acid may be defined as an acid that occurs in a natural
triglyceride and is a mono carboxylic acid ranging in chain length
From four carbon to 24 carbon atoms and including , with
exceptions, only the even-numbered members of the series

Figure 44

Some Natural Fatty Acids

Hydroxy acids : ricinoleic acid and dihydroxy stearic acid (castor

oil) cerebronic acid (C23H46[OH]COOH, 2 hydroxy tetracosanoic
acid) (cerebroside of animal tissues)
Cyclic acids: Hydnocarpic and chaunmoogric acids (chaulmoogra
oil, used in treatment of leprosy)
Linoleic acid, linolenic acid and arachidonic acid are essential
fatty acids

Figure 45
Obviously other combinations are possible, and are
known as configurational isomers. They each will differ;
for example the following:
H3C

CH3CH2CH2COOH

CHCOOH
H3C

Butyric acid

Isobutyric acid

Oleic acid is 9; linoleic acid is 9,12, -linolenic acid

is 6,9,12, arachidonic acid is 5,8,11,14.
CH3(CH2)7 C H

CH3(CH2)7 C H
H C (CH2)7COOH
trans
Elaidic acid

HOOC(CH2)7 C H
cis
Oleic acid

Natural unsaturated fatty acids are all cis isomers. The

schematic form of linoleic acid is as follows:
COOH

Linoleic acid

Figure 46

Hydrolysis

If Alkali is used (saponification):

Triolein + 3NaOH

Glycerol + 3C17H33COO-Na+ (Sodium oleate, soap)

Phospholipids

They are first and foremost structural components

of membranes
Serves as emulsifying agents and surface active
agents
They are amphipathic molecules
They are of two types : phosphoglycerides and
spingomyelins (contains spingosine instead of
glycerol)
Ceramide is the core structural unit of spingolipids
which is a fatty acid amide derivative of spingosine

Ceramide is the core structural unit of spingolipids

which is a fatty acid amide derivative of spingosine

Figure 47

Table 10.2 Major Classes of Phospholipids

Figure 48

Components of Sphingolipid

Steroids
Contains cyclopentanoperhydrophenanthrene
ring
It is the nonsaponifiable fraction of lipids
Main constituent of animal tissues and
abundant
in brain, nerve tissue and glandular
tissue
Chief component of gallstones
Normal blood level is 200 mg/ml a portion of
which is plasma protein bound

Figure 49

The Structure of cholesterol

21

22

H3C
18

20

CH3
12

19

11

CH3
1
2

HO

9
10

5
4

B
6

8
7

14

23

CH3
25

CH3
26

17
13

27

24

16
15

Figure 50

and Forms of Cholesterol

Key Words of Todays Lecture

Lipid
Triglycerol
Fatty Acid
Phospholipid
Spingolipid
Cholesterol

Eicosanoids
Extremely powerful hormone like molecules but are not
hormones rather autocrine regulators
Derived from arachidonic acid which is synthesized
from linoleic acid by adding a two carbon unit and inserting
two
additional double bonds
Phospholipase A2 release arachidonic acid from
membrane
phopholipid to initiate eicosanoid synthesis
Prostaglandins , thromboxanes and leukotrienes are
the
three types of eicosanoids

Figure 51

Selected Examples of Eicosanoids

Key Features of Eicosanoids

Prostaglandins contains a cyclopentane ring with hydroxy
group at C - 11 and C - 15 (pain, fever, ovulation, uterine
contraction, gastric secretion inhibition)
Thromboxanes possess a cyclic ether in their structures;
TxA2 is the most prominent member of this group and is
primarily produced by platelet (clotting)
Leukotrines
are
hydroxy
derivatives
possessing
conjugated
trienes ; early discovery was in leukocites.
LTC4, LTD4
and LTE4 are slow - releasing substance of
anaphylaxis ( SRS - A ) , cause fluid leakage from blood
vessels to
inflamed area. LTB4 is a potent chemotactic
agent

Figure 52

Biological Actions of Selected

Eicosanoid Molecules

Lipoproteins
Proteins covalently linked to lipid found in the blood plasma

Key concepts
Plasma lipoproteins transport lipid through the bloodstream. On the
basis of density, lipoproteins are classified into four major classes:
Chylomicrons: Large lipoproteins of extremely low density; transport
dietary triglycerols and cholesteryl esters from intestine to the tissues
(muscle/ adipose)
VLDL (0.95-1.006 g/cc) : synthesized in the liver ; transport lipids to
tissues; coverted to LDL with depletion of triglycerol, apoproteins and
phospholipids
LDL (1.006 - 1.063 g/cc): carry cholesterol to tissues; engulfed by
cells
after binding to LDL receptors
HDL (1.063 - 1.210 g/cc ): produced in liver; scavenge cholesterol
from
cell membrane as cholesteryl ester which is transported to liver
from
where the excess cholesterol is disposed of as bile acids

Atherosceloresis is A chronic disease in which soft masses

called atheromas, accumulate on the inside of arteries

Complex

Source

Density
(g/ml)

%Protei
n

%TGa

%PLb

%CEc

%Cd

%FFAe

Chylomicro
n

Intestin
e

<0.95

1-2

85-88

VLDL

Liver

0.951.006

7-10

50-55

18-20

12-15

8-10

IDL

VLDL

1.0061.019

10-12

25-30

25-27

32-35

8-10

LDL

VLDL

1.0191.063

20-22

10-15

20-28

37-48

8-10

*HDL2

Intestin
e, liver
(chylom
icrons
and
VLDLs)

1.0631.125

33-35

5-15

32-43

20-30

5-10

*HDL3

Intestin
e, liver
(chylom
icrons
and
VLDLs)

1.1251.21

55-57

3-13

26-46

15-30

2-6

AlbuminFFA

Adipose
tissue

>1.281

99

100

Triacylglycerols, bPhospholipids, cCholesteryl esters, dFree cholesterol, eFree fatty acids

*HDL2 and HDL3 derived from nascent HDL as a result of the acquisition of cholesteryl esters
a

Figure 53

General Structure of Plasma

Lipoproteins

Figure

54

A Summary of the Relative Amounts of Cholesterol,

Cholesteryl Ester, Phospholipid, and Protein in Four
major Classes of Plasma Lipoproteins

Membrane Lipids
According to the fluid mosaic medel, membrane is a lipid bilayer;
proteins float within the bilayer and determines the membranes
biological function
Chemical Composition of Some Cell Membranes
Membrane
Human erythrocyte plasma membrane
Mouse liver cell plasma membrane
Amoeba plasma membrane
Mitochondrial inner membrane
Spinach chloroplast lamellar membrane
Halobacterium purple membrane

Protein Lipid
(%)
(%)
49
46
54
76
70
75

43
54
42
24
30
25

Carbohydrate
(%)
8
2-4
4
1-2
6
0

Figure 55

Structure of Lipid Bilayer

Figure 56

Membrane Structure

Majority of membrane lipids are phospholipids which are largely

responsible for following biological events of membranes:
1.

Membrane fluidity

2.

Selective permeability

3.

Self-sealing capability

4.

Asymmetry

Key Words of Todays Lecture

Eicosanoids
Prostaglandins
Thromboxanes
Leukotrienes
Plasma Lipoproteins
Membrane Lipids

Metabolism
The hydrophobic and highly reduced structure of triglycerols allows
them to serve as a compact and rich source of energy (e.g., in
average U.S. diet, 30 40% of calories are provided by fat). The
metabolism of lipids include the degradation and synthesis and
regulation of these processes. A major emphasis is placed on the
role of the central metabolite in lipid metabolism: acetyl-CoA.

Figure 57

Oxidation
1. ACTIVATION
Thiokinases also known as Acyl-CoA ligase
activate the fatty acids to fatty acyl-CoA
Thiophorases activate by interconversion
O

+ RCH2CH2COOH

+ ATP

Mg++

[RCH2CH2C

+ PPi

[RCH2CH2C

AMP]

AMP]

RCH2CH2C

+ HSCoA

SCoA + AMP + E

RCH2CH2COOH + ATP + HSCoA

Mg
E

++

RCH2CH2C

SCoA + AMP + PPi

2. Acyl-CoA Translocation:
Role of Carnitine
Acyl - CoA ligase is found in the outer mitochondrial membrane.
Mitochondrial inner membrane is impermeable to most acyl-CoA and
carnitine is used to transport these acyl groups as follows:
CoASH

Fatty Acyl-Carnitine

CH3

CoASH
H3C

Fatty Acyl-CoA

Carnitine

Outer Membrane

Fatty Acyl-CoA
Inner Membrane

N+
CH3

O
H2
C

H
C

H2
C

OH

Carnitine

Each acyl - CoA is converted to acylcarnitine; carnitine

acyltransferase I catalyze this reaction
A carrier protein within the mitochondrial inner membrane
transfers acylcarnitine into the mitochondrial matrix
Acyl - CoA is regenerated by carnitine acyltransferase II
Carnitine is transported back into the inner membrane by
carrier protein and the cycle goes on

O-

Figure 58

-Oxidation of Acyl-CoA

Stoichiometry for
Palmitic Acid Oxidation
O
CH3(CH2)14C

CoA + 7FAD + 7NAD+ + 7CoASH + 7H2O

S
O

8 CH3C

CoA + 7FADH2 + 7NADH+ + 7CoASH + 7H+

Each FADH2 yield 1.5 ATP and NADH 2.5 ATP during electron
transport and oxidative phosphorylation, acetyl CoA yields 10ATP
thus a total of 108ATP of which 2 ATP is utilized in conversion of
palmitic acid to Palmityl-CoA, thus 106 molecules ATP per
molecule of palmitic acid is synthesized

Oxidation of Unsaturated Fatty

Acids
Similar pathway as above
Usually natural unsaturated fatty acids have cis
configuration, which is transformed to trans by the action of
an isomerase, as enoyl hydrates acts only on trans double
bonds.
An epimerase is needed to form L-isomer as D-isomer of 3hydroxy fatty acyl-CoA is formed when enoyl hydrases acts
on 2,3 unsaturated fatty acid

Figure 59

Oxidation of Odd-chain Fatty Acids

Conversion of Propionyl-CoA to Succinyl-CoA
End product of -oxidation of an odd-number fatty acid is acetylCoA and a propionyl-CoA. The propionyl-CoA is then converted to
succinyl-CoA, a citric acid cycle intermediate

Ketone Bodies
Most of the acetyl-CoA product during fatty acid oxidation is utilized
by the citric acid cycle or in isoprenoid synthesis. In a process
called ketogenesis, acetylCoA molecules are used to synthesize
acetoacetate, -hydroxy butyrate and acetone, a group of molecules
called the ketone bodies
Ketone body formation occurs within mitochondria
Ketone bodies are used to generate energy by several
Tissues, e.g., cardiac and skeletal muscle and brain

Figure 60

Ketone Body Formation

Figure 61

Conversion of Ketone
Bodies to Acetyl-CoA

Ketosis
In normal metabolic pathway, acetoacetate and hydroxybutyrate are the ketone bodies which are
converted to acetyl - CoA. However, during
starvation and in uncontrolled diabetes, conc. of
acetoactate is very high and supply of oxaloacetate
(a TCA component) is insufficient, thus acetoacetate
spontaneously decarboxylated to acetone KETOSIS
A 4-carbon acid (oxaloacetate) is needed to react with excess
acetyl-CoA and form citrate
When OAA is not available excess acetyl - CoA in liver are
condensed to form ketone bodies
OAA is limited during scarcity of glucose for glycolysis. In
starvation and diabetes, glycogen is broken down. Fatty acids of
fat depots are metabolized to supply ATP needs producing
excess of the ketone bodies

Key Words of Todays Lecture

-Oxidation
Carnitine
Acyl-CoA & acetyl-CoA
Propionyl-CoA & Succinyl-CoA
Ketone Bodies
Ketosis

Which is responsible for the

transporting of fatty acid across the
mitochondrial inner membrane?
1.
NADH
2.
Plasmin
3.
Cyctochrome Q
4.
Carnitine

hydroxyacyl-CoA dehydrogenase, 3. betaketothiolase, 4. Enoyl hydrase, 5. Thiokinase.

Which is the order of the enzyme involved?
A.
1, 2, 3, 4, 5
B.
2, 3, 4, 5, 1
C.
5, 2, 4, 1, 3
D

Ketosis is ascribed in part to:

A. Slowdown in fat metabolism
5, 1, 4, 2, 3
B. An insufficient
intermediates
of TCAE.cycle
Beta-oxidation
of octanoic
acid in mitochondria
yields:
C. An underproductionA.of acetyl-SCoA
D. A vigorous protein synthesis
3, 2, 4, 1, 5
E. An1 inhibition
glycogen
FADH2, 1ofNADH
and synthesis
1 acetyl-CoA
B.
2 FADH2, 2 NADH and 2 acetyl-CoA
C.
2 FADH2, 2 NADH and 3 acetyl-CoA
D.
3 FADH2, 3 NADH and 3 acetyl-CoA

A fatty acid with an odd number of carbons will enter the citric acid cycle as acetylCoA and:
A.
-ketoglutarate
B.
Malate
C.
Succinyl-CoA
D.
Citrate
E.
Butyrate
Which of the following statements apply to the -oxidation of fatty acids?
A.
The process takes place in the cytosol of mammalian cells.
B.
Carbon atoms are removed from the acyl chain one at a time.
C.
Before oxidation, fatty acids must be converted to their CoA derivatives.
D.

Biosynthesis of Lipids

Formation of Malonyl-SCoA
This is considered as activation step as the breaking of the CO2 bond of
malonyl-SCoA releases lot of energy that drives the reaction forward
Mg++

HCO3- + ATP + biotinyl-enzyme

ADP + Pi + carboxy-biotinyl-enzyme

carboxy-biotinyl-enzyme + H3C

SCoA

HOOCH2C

SCoA + biotinyl-enzyme
O

O
-

HCO3 + ATP +H3C

SCoA

Mg++

ADP + Pi + HOOCH2C
biotinyl-enzyme

O
-

H2C

C
O

OO

SCoA

NH

NH3+

O
S

(CH2)4

H
N

(CH2)4

carboxy-biotinyl-enzyme

SCoA

Figure 62

Fatty Acid Biosynthesis

Figure 63

Diagrammatic View of
Fatty Acid Biosynthesis

Stoichiometry for Palmitic Acid

Synthesis
O

CH3C

SCoA + HOOCCH2C

SCoA + 14NADPH + 14H+

O
CH3(CH2)14C

+
OH + 14NADP + 8CoASH + 6H2O + 7CO2

From acetyl-CoA
O

8 CH3C

SCoA + 7CO2 + 7ATP + 14NADPH + 14H+

O

CH3(CH2)14C

+
OH + 14NADP + 7CO2 + 8CoASH + 6H2O + 7ADP + 7Pi

Lipogenesis and Lipolysis

Fatty acid may be converted to triacylglycerol, degradated to
generate energy, or utilized in membrane synthesis
When serum glucose level is high after meal, insuline promotes
triacylglycerol synthesis by facilitating the transport of glucose
into adipocytes - lipogenesis
Adiposites can not synthesize triacylglycerol when glucose level
is low (between meal), when several hormones stimulate the
hydrolysis of triacyl-glycerol within adipose tissue to form
glycerol and fatty acids lipolysis.

Figure 64

Triacylglcerol Synthesis

Figure 65

Biosynthesis of Phosphatidic
Acid and Triglyceride

Lipolysis
Lipolysis occur during fasting, vigorous exercise, and in response to
stress.

Binding

of

several

hormones

(e.g.,

glucagon

and

epinephrine) to specific adipocyte plasma membrane receptors

initiates a reaction sequence similar to the activation of glycogen
phosphorylase. As a result of cAMP synthesis, the enzyme
triacylglycerol lipase (hormone-sensitive lipase) is activated when it
is phosphorylated by protein kinase which is activated by cAMP
NH2

N
N

H
O
O

R
R

HO

O
O

OH

Figure 66

Lipolysis Diagrammatic View

Figure 67

Synthesis of Selected Steroids

Key Words of Todays Lecture

Biosynthesis of lipid
Malonyl-SCoA
Fatty Acid Synthesis
Triacylglycerol
Phosphatidic Acid
Lipogenesis & Lipolysis
Steroid Synthesis

In the conversion of acetyl-CoA to malonyl-CoA

B.
In the conversion of malonyl-CoA to malonic acid
C.
To prevent the oxidation of biotin
D.
Which statement about lipogenesis and lipolysis is true
In
formation
of acetyl-CoA
fromtopyruvate
A. theFatty
acid may
be converted
triacylglycerol
E.
B. After meal, insuline promotes lipogenesis
C. Between meal, several hormones stimulate lipolysis
In
of amino acid
D. theBdeamination
&C
E. A, B & C
A.Which statement is NOT true to the biosynthesis of palmitic acid:
A. Carboxylation of acetyl CoA to form malonyl CoA initiates its biosynthesis
B. 1 molecule of Acetyl CoA, 7 molecules of malonyl CoA and 14 NADPH are
needed to synthesize 1 molecule of palmitic acid
C. 8 molecules of malonyl CoA and 14 NADPH are needed to synthesize 1
molecule of palmitic acid
D. Its biosynthesis occurs in citosol
E. NADPH is the coenzyme in the reduction steps
O
17--Hydroxylase 17-a-Hydroxy 17,20-Lyase
Progesterone
progesterone
O
4-Androstenedione

17-b-Hydroxysteroid
dehydrogenase

Testosterone