Fatty acid synthesis

1. Fattyacid synthesis
Dr.M.Sabarinathan M.Sc.,PhD
Department of Biochemistry

2. Introduction
 Fatty acids are synthesized mainly by a de novo
synthetic pathway operating in the cytoplasm.
 The major fatty acid synthesized de novo is
palmitic acid, the 16C saturated fatty acid.
 The process occurs in liver, adipose tissue, kidney,
brain, and mammary glands.

3. Steps
 The fatty acid synthesis may be learnt in 3
stages
 I. Production of acetyl CoA and NADPH
 II. Conversion of acetyl CoA to malonyl
CoA
 III. Reactions of fatty acid synthase
complex.

4. I. Production
of acetyl CoA
and NADPH
 Acetyl CoA and NADPH are the prerequisites for
fatty acid synthesis.
 Acetyl CoA is the source of carbon atoms while
NADPH provides the reducing equivalents and ATP
supplies energy for fatty acid formation.
 It is produced in the mitochondria by the oxidation
of pyruvate and fatty acids, degradation of carbon
skeleton of certain amino acids, and from ketone
bodies.
 Mitochondria are not permeable to acetyl CoA

5. Transport of
Acetyl CoA
to
Cytoplasm

6. II. Formation
of malonyl
CoA
 Acetyl CoA is carboxylated to malonyl CoA by the
enzyme acetyl CoA carboxylase
 This is an ATP-dependent reaction and requires
biotin for CO2 fixation.

7. Fatty Acid
Synthase
(FAS)
Complex
 This system exists as a multi-enzyme complex.
 The enzymes form a dimer with identical
subunits.
 Each subunit of the complex is organized into 3
domains with 7 enzymes
 Advantages of Multi-enzyme Complex
 a. Intermediates of the reaction can easily
interact with the active sites of the enzymes.
 b. One gene codes all the enzymes; so all the
enzymes are in equimolecular concentrations.
 c. So the efficiency of the process is enhanced.

8. Fatty Acid Synthase (FAS) Complex

9. III. Reactions
of fattyacid
synthase
complex
 1. The acetyl unit is then transferred from ACP to
cysteine residue of the enzyme.
 It is catalysed by the enzyme, acetyl CoA-ACP
transacylase.
 2. The enzyme malonyl CoA-ACP transacylase
transfers malonate from malonyl CoA to bind to
ACP.
 3. The acetyl unit attached to cysteine is transferred
to malonyl group.
 This reaction is catalyzed by β-ketoacyl ACP
synthase.

10. III. Reactions
of fattyacid
synthase
complex
 4. β -Ketoacyl ACP reductase reduces
 ketoacyl group to hydroxyacyl group. The
 reducing equivalents are supplied by NADPH.
 5. β -Hydroxyacyl ACP undergoes dehydration.
 A molecule of water is eliminated and a double
 bond is introduced.
 6. A second NADPH-dependent reduction,
catalysed by enoyl-ACP reductase occurs to produce
acyl-ACP.
 The four-carbon unit attached to ACP is butyryl
group.

11. III. Reactions
of fattyacid
synthase
complex
 7. The carbon chain attached to ACP is transferred
to cysteine residue and the reactions 2-6 are
repeated 6 more times.
 Each time, the fatty acid chain is lengthened by a
two-carbon unit
 8. The enzyme palmitoyl thioesterase separates
palmitate from fatty acid synthase.
 This completes the synthesis of palmitate.

13. Regulation
 Fatty acid production is controlled by
 enzymes, metabolites, end products, hormones
 and dietary manipulations.
 Acetyl CoA carboxylase : This enzyme
 controls a committed step in fatty acid synthesis.
 Hormonal influence : insulin promotes fatty acid
 synthesis while glucagon inhibits.

14. Dietary
regulation
 Consumption of high carbohydrate or fat-free diet
increases the synthesis of acetyl CoA carboxylase
and fatty acid synthase, which promote fatty acid
formation.
 On the other hand, fasting or high fat diet
decreases fatty acid production by reducing the
synthesis of these two enzymes.

15. Availability
of NADPH
 The reducing equivalents for fatty acid synthesis
are provided by NADPH which come either from
citrate (acetyl CoA) transport or hexose
monophosphate shunt.
 About 50-60% of required NADPH is obtained
from HMP shunt, which significantly influences
fatty acid synthesis.