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Biosynthesis of Fatty Acids

Fatty acid biosynthesis is crucial for energy storage and cellular membrane composition, primarily occurring in the liver, kidney, adipose tissue, and lactating mammary glands. The process involves the production of acetyl CoA and NADPH, conversion of acetyl CoA to malonyl CoA, and reactions catalyzed by the fatty acid synthase complex, which is regulated by various enzymes, hormones, and dietary factors. In higher eukaryotes, this synthesis takes place in the cytosol, with NADPH serving as the primary electron carrier.

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8 views11 pages

Biosynthesis of Fatty Acids

Fatty acid biosynthesis is crucial for energy storage and cellular membrane composition, primarily occurring in the liver, kidney, adipose tissue, and lactating mammary glands. The process involves the production of acetyl CoA and NADPH, conversion of acetyl CoA to malonyl CoA, and reactions catalyzed by the fatty acid synthase complex, which is regulated by various enzymes, hormones, and dietary factors. In higher eukaryotes, this synthesis takes place in the cytosol, with NADPH serving as the primary electron carrier.

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Fatty acid biosynthesis

Fatty acid biosynthesis


 Lipids play a variety of cellular roles.
 They are the principal form of stored energy in most
organisms and major constituents of cellular
membranes.
 Specialized lipids serve as pigments (retinal,
carotene), cofactors (vitamin K), detergents (bile
salts), transporters (dolichols), hormones (vitamin D
derivatives, sex hormones) extracellular and
intracellular messengers (eicosanoids).
De novo (new) synthesis of fatty acids occurs predominantly in
liver, kidney, adipose tissue and lactating mammary glands.
The enzyme machinery for fatty acid production is located in
the cytosomal fraction of the cell. Acetyl CoA is the source of
carbon atoms while NADPH provides the reducing equivalents
and ATP supplies energy for fatty acid formation.

The fatty acid synthesis may be learnt in 3 stages


l. Production of acetyl CoA and NADPH
ll. Conversion of acetyl CoA to malonyl CoA
lll. Reactions of fatty acid synthase complex.
l. Production of acetyl CoA and NADPH
Acetyl CoA and NADPH are the prerequisites for fatty acid synthesis. Acetyl CoA 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, however, are not permeable to acetyl CoA. An alternate or a bypass
arrangement is made for the transfer of acetyl CoA to cytosol. Acetyl CoA condenses
with oxaloacetate in mitochondria to form citrate. Citrate is freely transported to cytosol
where it is cleaved by citrate lyase to liberate acetyl CoA and oxaloacetate. Oxaloacetate
in the cytosol is converted to malate (Fig.14.14).
ll. Formation of malonyl CoA

Acetyl CoA is carboxylated to malonyl CoA by the enzyme acetyl CoA


carboxylase
Fig. 14.15. This is an ATP-dependent reaction and requires biotin for CO2 fixation
Acetyl CoA carboxylase is a regulatory enzyme in fatty acid synthesis.
lll. Reactions of fatty acid synthase complex

The remaining reactions of fatty acid synthesis are catalysed by multifunctional


enzyme known as fatty acid synthase (FAS) complex.

In eukaryotic cells, including man, the fatty acid synthase exists as a dimer with
two identical units. Each monomer possesses the activities of seven different
enzymes and an acyl carrier protein (ACP) bound to 4'-
phosphopantetheine.

Fatty acid synthase functions as a single unit catalyzing all the seven reactions.
Dissociation of the synthase complex results in loss of the enzyme activities.

In the lower organisms (prokaryotes), the fatty acid synthesis is carried


out by a multienzyme complex in association with a separate acyl carrier
protein. This is in contrast to eukaryotes where ACP is a part of fatty acid
synthase.
8Acetyl CoA + 7 ATP + 14 NADPH + 14 H+
- Palmitate+ 8 CoA + 7 ADP + 7 Pi +
6H2O
Regulation of fatty acid synthesis
Fatty acid production is controlled by enzymes, metabolites, end products, hormones
and dietary manipulations. Some of the important regulatory mechanisms are discussed
hereunder.
Acetyl CoA carboxylase : This enzyme controls a committed step in fatty acid
synthesis. Acetyl CoA carboxylase exists as an inactive protomer (monomer) or an active
polymer. Citrate promotes polymer formation, hence increases fatty acid synthesis. On
the other hand, palmitoyl CoA and malonyl CoA cause depolymerization of the enzyme
and, therefore, inhibit fatty acid synthesis.
Hormonal influence : Hormones regulate acetyl CoA carboxylase by a separate
mechanism-phosphorylation (inactive form) and dephosphorylation (active form) of the
enzyme. Glucagon, epinephrine and norepinephrine inactivate the enzyme by cAMp-
dependent phosphorylation. Insulin, on the other hand, dephosphorylates and activates
the enzyme. Thus, insulin promotes fatty acid synthesis while glucagon inhibits.
Insulin stimulates tissue uptake of glucose, and conversion of pyruvate to acetyl CoA.
This also facilitates fatty acid formation.
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.
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.
Fatty acid biosynthesis-
location
 In higher eukaryotes, the fatty acid synthase complex is
found exclusively in the cytosol.
 In plants, fatty acid synthesis occurs in the chloroplast
stroma.
 Usually, NADPH is the electron carrier for anabolic
reactions.
 NAD+ serves in catabolic reactions.
 In hepatocytes and adipocytes, cytosolic NADPH is
largely generated by the pentose phosphate pathway
and malic enzyme

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