Draft: Fatty Acid Synthesis

Fatty acid synthesis is mainly carried out in the cytoplasm of liver cells. It is not the reverse of fatty acid oxidation 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. Carbons are transported out to the cytoplasm indirectly as citrate, which is then recreated into acetyl-CoA once outside. The acetyl-CoA is then carboxylated to form malonyl-CoA by the enzyme acetyl-CoA carboxylase (ACC). Malonyl-CoA is the actual direct substrate of fatty acid synthesis. Synthesis is carried out by the enzyme fatty acid synthase (FAS), which acts as a dimer that makes two fatty acid chains at once. First the cysteine amino acid on FAS is primed, and then sequential cycles of reactions create the fatty acid. Each cycle adds two carbons from malonyl-CoA using the energy from NADPH. Seven cycles produce a 16-carbon chain, and all fatty acid chains produced by FAS are 16:0. Elongation and desaturation to create other fatty acids are carried out by additional enzymes. Double bonds are added by the enzyme desaturase; although, human enzymes cannot form double bonds past the tenth carbon. Fatty acids with double bonds past the tenth carbon are acquired solely through diet.