Fatty_acid_synthesis

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Fatty acid synthesis

Fatty acids are formed by the action of Fatty acid synthases from acetyl-CoA and malonyl-CoA precursors.

De Novo Synthesis in Humans

In humans fatty acids are predominantly formed in the liver and adipose tissue, and mammary glands during lactation. Most acetyl-CoA is formed from pyruvate by pyruvate dehydrogenase in the mitochondria. Acetyl-CoA produced in the mitochondria is condensed with oxaloacetate to form citrate, which is then transported into the cytosol and broken down to yield acetyl-CoA and oxaloacetate by ATP citrate lyase.

Elongation

Much like β-oxidation, elongation occurs via four recurring reactions shown below. In these diagrams, the acetyl and malonyl units are shown as their Acyl carrier protein thioesters: this is how fatty acids are synthesized in microorganisms and plants. However, in animals these same reactions occur on a large dimeric protein, Fatty acid synthase, which has the full complement of enzymatic activities required to synthesize and liberate a free fatty acid.

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.		β-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.