Malonyl-CoA

Malonyl-CoA is a coenzyme A derivative which plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. In the former, it provides 2-carbon units to fatty acids and commits them to fatty acid chain synthesis.

Malonyl-CoA is formed in the metabolism from the carboxylation of acetyl-CoA by the enzyme acetyl-CoA carboxylase. One molecule of acetyl-CoA is joined with a molecule of carbon dioxide, requiring energy rendered from ATP

Malonyl-CoA is utilised in fatty acid biosynthesis by the enzyme malonyl coenzyme A:acyl carrier protein transacylase (MCAT). MCAT serves to transfer malonate from malonyl-CoA to the terminal thiol of holo-acyl carrier protein (ACP).

Controversy still exists whether MCAT is also involved in bacterial polyketide biosynthesis, however there is evidence that the acyl carrier protein from a variety of bacterial polyketide synthases is capable of self malonylation in the presence of malonyl-CoA.

Malonyl-CoA is a highly regulated molecule in fatty acid synthesis; as such, it inhibits the rate-limiting step in beta-oxidation of fatty acids: the association of coenzyme A with carnitine. This step permits coenzyme A to enter the mitochondria and regulation prevents simultaneous synthesis and breakdown of fatty acids.