It mainly contains metabolism of saturated and unsaturated fats. It also contains utilisation of cholesterol after degradation in body i.e. synthesis of bile acids, Vit. D, steroid hormone etc. It also describe synthesis of ketone bodies and utilisation.

1. Fatty acid metabolism
Shobha Singh,
M. Pharm., Ph. D.
Associate Professor

2. There are different types of oxidation takes place inside the body.
Beta oxidation takes place in mitochondria
Alpha oxidation in endoplasmic reticulum and peroxisomes
Omega-oxidation occurs in endoplasmic reticulum and microsomes.
Odd chain fatty acid occur in mitochondria
Site-Mitochondria, liver, adipose tissue, muscle
There are three steps involved in beta oxidation
 1- Activation of fatty acid
 2- Transport of fatty acid in mitochondria
 3- Beta oxidation proper
Steps
Four important steps
Oxidation- Acyl coA dehydrogenase
Hydration
Oxidation
Cleavage
Fatty acid oxidation

3. R-CH2-CH2-CH2-COOH
R-CH2-CH2-CH2-COAMP
(acyl adenylate)
Thiokinase
R-CH2-CH2-CH2-CO-SCOA
Acyl COA
1. Activation of Fatty acid ( Cytosol)
2. Transport of Acyl CO A to mitochondria

4. 3. Beta-oxidation proper of fatty acid
4. Bioenergetics: Palmitoyl COA + 7NAD+ + 7FAD+ + 7H2O 8Acetyl COA +
7NADH + 7FADH2 + 7H+
8 Acetyl CoA- 8X10 = 80 ATP
7NAD+ = 7X2.5
7FAD+ = 7X1.5 TOTAL = 108ATP-2ATP = 106ATP

5. DE NOVO Synthesis of Fatty acids
De Novo synthesis takes place in
Liver
Kidney
 Adipose tissue
Some of dietary compounds like
carbohydrates, amino acid when
consumed in excess quantity, they get
converted into fatty acids and they will be
stored as triglycerides.
De Novo synthesis takes place in three
stages
1. Production of Acetyl COA and NADPH
2. Conversion of Acetyl COA into malonyl
CO A
3. Reactions of fatty acid synthase
complex
1. Production of Acetyl COA and NADPH
 Acetyl CoA is the main requirement for the production of fatty acids. Mainly we get
Acetyl CoA by the oxidation of pyruvate in mitochondrial matrix and from amino
acids and from ketone bodies.
 The reaction which is taking place in mitochondria that is impermeable to Acetyl Co A.
So it transfer Acetyl CoA alternative arrangement is made.
 Acetyl CoA is condensed to oxaloacetate and form the the citrate. The formed citrate
easily transported out of the mitochondial matrix to cytosol. The formed citrate
undergoes series of reaction with particular enzymes and produces fatty acids.

6. 2. Conversion of Acetyl to malonyl CoA
a. Acetyl CoA undergoes carboxylation
reaction to produce malonyl CoA.
b. This is an ATP dependent reaction and
requires biotin for CO2 fixation.
Acetyl Co A
CO2 + ATP
ADP+Pi
Malonyl Co A
Acetyl Co A
carboxylase,
Biotin

7. 3. Reactions of fatty acid synthase complex
a. Reaction of fatty acid synthase are catalyzed by multifunctional enzyme known as fatty acid synthase
(FAS) complex
b. Each monomer possesss the activity of different enzyme and an acyl carrier protein.
c. This sequence of reaction will be discussed below.

8. FAS COMPLEX
Summary of reactions: 2 carbon comes only from Acetyl Co A and 14 comes from malonyl Co
A.
8 Acetyl Co A + 7 ATP + 14 NADPH + 14 H+ Palmitate + 8 CoA + 7 ADP + 7Pi
+ 6H2O

9. CHOLESTEROL
 Cholesterol often found exclusively in animals so that it is known as animal sterol.
 It is amphipathic in nature.
Functions:
1. It is structural component of cell membrane.
2. It is precursor for the synthesis of all other steroids in the body. These include steroid
hormone, vitamin D and bile acids.
3. It is an essential ingredient in the synthesis of lipoproteins.
4. Cholesterol synthesis takes place mainly in liver (50%) and intestine (15%) , almost all the
organs.
5. Synthesis of cholesterol takes place in five stages
a. Synthesis of HMG CoA
b. Formation of mevalonate ( 6C)
c. Production of isoprenoid units (5C)
d. Synthesis of squalene
e. Conversion of squalene into cholesterol

10. DEGRADATION OF CHOLESTEROL
 50% cholesterol is converted to bile acids, excreted in feces, serve as precursor for the
synthesis of steroid hormones, vit-D.
1. Synthesis of bile acids
 Bile acids are synthesized in liver form cholesterol.
 It possess 24 carbon, 2 0r 3 OH groups in steroid nucleus and side chain contain
carboxylic group at end.
 Bile acids are amphipathic in nature i. e. possess polar and non-polar group.

11.  Serve as emulsifying agent in intestine.
 Participate in digestion and absorption of lipid.
Hydroxylation reactions.
 Cholesterol is converted in to 7-hydroxycholesterol by action of 7α-hydroxylation.
 Synthesiss of primary bile acids take place in liver and involve a series of reactions.
 This step catalyzed by 7α-hydroxylation and inhibited by bile acids and rate limiting step.
Cholic and chenodeoxycholic acids are the primary bile acids.
 On conjugation with glycine or taurine, conjugated bile acids are formed which are used
as efficient sutfactant.
 In intestine, a portion of primary bile acids undergo deconjugation and dehydroxylation
to form secondary bile acids (deoxycholic acid and lithocholic acid)

12. Synthesis of steroid hormone from cholesterol
 Cholesterol is the precursor for the synthesis of all the five classess of steroid hormone.
 Gluco-corticoids e.g. Cortisol
 Mineralocorticoids e.g. aldosterone
 Prodestins e.g. Progesterone
 Androgens e.g. testosterone
 Estrogens e.g. estradiol

13. Synthesis of Vit-D
 7-Dehydro-cholestrol is an intermediate in the synthesis of cholesterol, is converted to
cholecalciferol (vit-D3) by ultraviolet rays in the skin.

14. KETOGENESIS AND KETONE BODIES
 Formation of ketone bodies in liver known as ketogenesis.
 Ketone bodies are acetone, acetoacetate and β-hydroxy-butyrate and energy yielding.
 Ketone bodies are formed in case of Diabetes mellitus and starvation condition.
 Enzymes for ketone bodies are located in mitochodria.
 They are water soluble and energy yielding.
 Ketone bodies are synthesized by two molecule of acetyl CO A combined and formed
acetoacetate COA. Reaction catalyzed by thiolase enzyme.
 Acetoacetyl Co A combine with another acetyl CoA and produce β-hydroxy- β-methyl
glutaryl CoA. HMG CoA synthase catalyse the reaction, regulate the synthesis of ketone
bodies.
 HMG CoA lyase cleaves HMG CoA to produce acetoacetate and acetyl CoA.
 Acetoacetate can be reduced by a dehydrogenase to β-hydroxybutyrate.