This document summarizes fatty acid synthesis. Key points include:
- Fatty acid synthesis occurs in the cytoplasm and is initiated by acetyl-CoA carboxylase converting acetyl-CoA to malonyl-CoA.
- A fatty acid synthase complex containing multiple enzymatic domains then catalyzes the steps of fatty acid elongation using malonyl-CoA, culminating in the formation of palmitic acid.
- The process is regulated by hormones like insulin and glucagon through effects on the activity of acetyl-CoA carboxylase.
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Fatty Acid Synthesis Pathway and Regulation
1.
2. First discovered by Feodor Lynen. Also known
as Lynen’s spiral.
It is not a reversal of oxidation.
Cellular site: Cytoplasm
Organ involved: Liver , kidney, adipose tissue,
brain and mammary gland.
Immediate precursor: Acetyl CoA.
Co-enzyme required: NADPH.
The major fatty acid synthesized is palmitic
acid.
7. Acetyl CoA carboxylase is rate limiting
enzyme.
Biotin is cofactor of the enzyme which is non-
covalently bond to enzyme.
Acetyl CoA Carboxylase
Acetyl CoA + CO2 Malonyl CoA
ATP Biotin ADP + Pi
8. The enzyme complex catalyzes the further steps of fatty
acid synthesis.
It is a dimer consisting of 2 identical subunit.
Each subunit consists of 7 different enzymes and Acyl
carrier protein(ACP).
The SH group of 4’phosphopantetheine of the ACP of
one monomer is in close proximity to the SH group of
cysteine residue of the ketoacyl synthase of other
monomer.
19. Step2A: Transfer of the acetyl group to cysteinyl SH
group of Ketoacyl synthase.
Step2B: Transfer of the Malonyl group to SH group of
ACP.
Step3: Condensation of acetyl and malonyl group to
from acetoacetyl-ACP.
Step4: Reduction
Step5: Dehydration
Step6: Reduction and formation of Butyryl-S-ACP
20. Cycling of reactions:
Butyryl group is transferred to the SH group of
condensing enzyme in other monomer. A
molecule of Manonyl will bind to SH group of
ACP in other monomer.
The sequence of reactions(3 to 6) are repeated
6 times for the synthesis of Palmitic acid(16C).
Tioesterase releases palmitate from multienzyme
complex.
21. Denovo synthesis of fatty acid in lactating
mammary gland forms medium chain fatty
acids{ Capric acid(10C) and Lauric acid(12C)}.
Palmitate is precursor for other long chain fatty
acids.
22. Short term regulation
1. Allosteric regulation
2.Covalent modification
Long term regulation
1.Hormonal regulation
2.Dietary regulation Induction/Repression