Fatty acid synthesis

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Fatty acids are formed by the action of Fatty acid synthases from acetyl-CoA and malonyl-CoA precursors. In humans fatty acids are predominantly formed in the liver and adipose tissue, and mammary glands during lactation. Most of acetyl-CoA is formed by Acetyl Co-A synthetase in the mitochondria and is transported into cytosol in the form of citrate.

Elongation

Much like β-oxidation, elongation occurs via four recurring reactions:

Step Description Diagram Enzyme
Condensation The first step is condensation of acetyl ACP and malonyl ACP. This results in the formation of acetoacetyl ACP. Although this reaction is thermodynamically unfavourable, the evolution of CO2 drives the reaction forward. beta-ketoacyl-ACP synthase
Reduction of acetoacetyl ACP In this step, acetoacetyl ACP is reduced by NADPH into D-3-Hydroxybutyryl ACP. The double bond is reduced to a hydroxyl group. Only the D isomer is formed. β-Ketoacyl ACP reductase
Dehydration In this reaction, D-3-Hydroxybutyryl ACP is dehydrated to crotonyl ACP. 3-Hydroxyacyl ACP dehydrase
Reduction of crotonyl ACP During this final step, crotonyl ACP is reduced by NADPH into butyryl ACP. enoyl ACP reductase

In the second step of elongation, butyryl ACP condenses with malonyl ACP to form an acyl ACP compound. This continues until a C16 acyl compound is formed, at which point it is hydrolyzed by a thioesterase into palmitate and ACP.

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