PP: Fatty Acid Synthesis

Fatty acid synthesis is primarily carried out in the cytoplasm of liver cells and involves multiple processes: (1) Acetyl-CoA transport, (2) malonyl-CoA formation, and (3) synthesis cycles. Acetyl-CoA is produced in the mitochondrial matrix and must be transported to the cytoplasm. It is transported indirectly as citrate, which is then converted back to acetyl-CoA once outside. The enzyme acetyl-CoA carboxylase (ACC) then carboxylates the acetyl-CoA to form malonyl-CoA, the direct substrate of fatty acid synthesis. Synthesis is carried out by fatty acid synthase (FAS), an enzyme that acts as a dimer to make two fatty acid chains simultaneously. First, the cysteine amino acid on FAS is primed. Then, sequential cycles of reactions create the fatty acid, each cycle adding two carbons from malonyl-CoA with energy from NADPH. Seven cycles produce a 16-carbon chain, and all fatty acid chains produced by FAS are 16:0. Additional enzymes are then required to elongate and/or desaturate the chain to form other fatty acids. The enzyme desaturase is responsible for adding double bonds, but it is incapable of forming double bonds past the tenth carbon. Therefore, fatty acids with double bonds past the tenth carbon are acquired solely through the diet.