Malonyl-CoA


Malonyl-CoA is a coenzyme A derivative of malonic acid.

Functions

It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis.

Fatty acid biosynthesis

In the former, it provides 2-carbon units to fatty acids and commits them to fatty acid chain synthesis.
Malonyl-CoA is formed by carboxylating acetyl-CoA using the enzyme acetyl-CoA carboxylase. One molecule of acetyl-CoA joins with a molecule of bicarbonate, requiring energy rendered from ATP.
Malonyl-CoA is utilised in fatty acid biosynthesis by the enzyme malonyl coenzyme A:acyl carrier protein transacylase. MCAT serves to transfer malonate from malonyl-CoA to the terminal thiol of holo-acyl carrier protein.

Polyketide biosynthesis

MCAT is also involved in bacterial polyketide biosynthesis. The enzyme MCAT together with an acyl carrier protein, and a polyketide synthase and chain-length factor heterodimer, constitutes the minimal PKS of type II polyketides.

Regulation

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. Malonyl-CoA inhibits fatty acids from associating with carnitine by regulating the enzyme carnitine acyltransferase, thereby preventing them from entering the mitochondria, where fatty acid oxidation and degradation occur.