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Fatty Acid Biosynthesis
Can occur in the cytoplasm of most animal cells, but
the liver is the major site for this process
Fatty acids are synthesized when the diet is low in fat
or high in carbohydrate or protein (most from
glucose via pyruvate)
A large quantity of NADPH is needed for this
process and is provided by the pentose
phosphate pathway and oxidation of malate to
form pyruvate by malic enzyme
Fatty Acid Biosynthesis
Similar to b-oxidation in reverse
Several notable differences:
1. Location occurs in
cytoplasm instead of
mitochondria and
peroxisome
2. Enzymes significantly
different than in boxidation
Comparison of the Phosphopantetheine Group in Acyl Carrier Protein
(ACP) and in Coenzyme A (CoASH)
3. Thioester linkage - intermediates are linked through a
thioester linkage to acyl carrier protein (ACP)
Acyl groups linked to ACP through phosphopantetheine
prosthetic group
4. Electron carriers consume NADPH
Fatty acid synthesis begins with the carboxylation of
acetyl-CoA to form malonyl-CoA
This is an activating reaction requiring ATP for the
carboxylation of biotin (Acetyl-CoA
carboxylase, ACC1)
Regulation of Acetyl-CoA
Carboxylase 1
ACC enzymes are highly regulated by allosteric
modulators and phosphorylation
Glucagon and AMPK lead to phosphorylation of ACC
which inactivates the enzyme
Insulin activates phosphoprotein phosphatase 2A
which activates ACC
glucagon
insulin
Citrate partially activates
hormonally inactivated carboxylase
The remaining
reactions of fatty acid
synthesis take place on
fatty acid synthetase
multienzyme complex
Site of seven enzyme
activities
Fatty Acid Synthase Structure
Two fatty acids
constructed
simultaneously
Formation of Acetyl-ACP
During the first three reactions, acetyl-CoA is
used to form malonyl-ACP, which is
converted to acetoacetyl-ACP by KSase
During the next three steps
(two reductions and a
dehydration), a butyryl
group is formed
Butyryl is then transferred
to KSase and the ACP-SH
group can bind another
malonyl group
Eventually synthesizes
palmitoyl-ACP
Fatty Acid Biosynthesis