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+ F.R.Fatty Acid Synthesis
+ F.R.Fatty Acid Synthesis
+ F.R.Fatty Acid Synthesis
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In general, the pathway of de novo synthesis is
used
in conditions of excess energy, & in
particular, carbohydrate intake.
In such conditions carbohydrates are
converted to fatty acids in the liver
stored as TAG in the adipose tissue
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Fatty acid synthesis occurs in the cytoplasm of
cells.
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Principal sources of NADPH + H+
1-Penthose phosphate pathway
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Principal
sources of
NADPH +
H+
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Principal sources of Acetyl CoA
1- The degradation of fatty acids
2-The degradation of amino acids.
3-The oxidation of pyruvate.
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Acetyl CoA is transported from mitochondria to
Cytosol by the following mechanism:
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This process of translocation of citrate from the
mitochondrion to the cytoplasm occurs when the
citrate concentration is high.
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Acetyl-CoA Carboxylase, is the committed (rate
limiting) step of the fatty acid synthesis pathway.
Step II
Reaction catalyzed by Fatty Acid Synthase
A Multienzyme Complex
This multifunctional enzyme catalyzes the seven
different reactions whereby two carbon units from
malonyl-CoA are linked together, ultimately to
form palmitoyl-CoA
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The enzyme complex can exist as both a monomer
and dimer.
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ACP contains the vitamin pantothenic acid in
the form of 4'-phosphopantetheine (Pant-SH) with
a thiol group at the end.
Pant Cyst
SH SH
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The sequence of reactions catalyzed by this
enzyme can be represented by the seven
following steps .
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3-The now-empty ACP accepts a 3C malonate unit
from malonyl CoA, malonyl CoA-ACP transacylase
catalyzes this reaction
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acetyl-S-CoA HS-CoA malonyl-S-CoA HS-CoA CO2
C O C O C O C O
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The sequence of reactions, namely condensation,
reduction, dehydration and reduction are repeated
six times, each time incorporating a two-carbon
unit (derived mainly from malonyl CoA) into the
growing fatty acid chain
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Product Release
When the fatty acid is 16 carbon atoms long, a
Thioesterase domain catalyzes hydrolysis of the
thioester linking the fatty acid to
phosphopantetheine.
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Regulation of FA Synthesis
1. Regulation of Acetyl CoA Carboxylase
Carboxylation of acetyl-CoA to malonyl-CoA is
the committed step of fatty acid
synthesis
This key lipogenic enzyme is subject to both
short term and long term regulation.
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1. Short-term control of fatty acid synthesis is
accomplished by
a) allosteric modifiers of synthetic enzymes.
Two of the most important regulated synthetic
enzymes are the following:
a).Acetyl CoA carboxylase, which is activated by
citrate and inhibited by malonyl CoA and
palmitoyl CoA
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Activated by citrate,
which increases in
well-fed state and is
an indicator of a
plentiful supply of
acetyl-CoA
Inhibited by long-
chain acyl-CoA
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b) Covalent modification.
Acetyl CoA carboxylase,
Glucagon promotes its phosphorylation
inactivation
Secretion of insulin promotes its
desphosphorylation activation
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Long-term control of fatty acid synthesis is
accomplished by regulating the synthesis of active
enzymes.
The synthesis of acetyl CoA carboxylase, fatty
acid synthase, citrate lyase, glucose 6 phosphate
dehydrogenase, and the malic enzyme
is decreased during fasting and
increased when glucose is again available in the
diet
Fat-free diets also lead to elevation of the levels
of these enzymes, resulting in increased fatty acid
synthesis
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-Oxidation & Fatty Acid Synthesis
Compared
-Oxidation Fatty Acid
Pathway Synthesis
Mitochondrial
Pathway location matrix
Cytosol
2-C
Acetyl -CoA Malonyl-CoA (& Acetyl
Product/Donor CoA)
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