Fatty acid synthesis

Route: Acetyl-CoA → Malonyl-CoA → Acetoacetyl-ACP → (3R)-3-Hydroxybutyryl-ACP → Crotonyl-ACP → Butyryl-ACP → Palmitoyl-ACP → Palmitate

Acetyl-CoA carboxylase adds CO₂ (as bicarbonate) to acetyl-CoA with the help of biotin and one ATP, which gives malonyl-CoA. This is the committing step. In the structure shown, the biotin carboxylase domain does the ATP-driven part. Humans make fatty acids with one large enzyme, fatty acid synthase (FASN), a single polypeptide that works as a dimer and carries every activity of the cycle. Its acetyl and malonyl groups sit on the acyl carrier protein (ACP), a domain of the same polypeptide. The growing chain is covalently linked to the sulfhydryl group of the ACP. The drawings show the chain on a one-atom stub that stands for that carrier. One turn has four steps. The ketoacyl synthase joins an acetyl group to a malonyl group and releases CO₂, which makes the four-carbon acetoacetyl chain. The ketoreductase uses NADPH to turn the ketone into a hydroxyl group. The dehydratase removes water and leaves a double bond. The enoyl reductase uses a second NADPH to saturate it, which gives butyryl. The chain then moves back to the synthase, picks up another malonyl group and turns again. Seven turns in total, starting from one acetyl group and seven malonyl groups, make the 16-carbon palmitoyl chain, and a thioesterase domain releases it as palmitate. The structure shown is the core modifying region of human FASN.

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Steps

Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).