Малонил КоА: Май қышқылдары мен поликетидтер биосинтезіндегі рөлі

Malonyl CoA is a coenzyme A derivative of malonic acid.

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

Malonyl CoA 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). MCAT serves to transfer malonate from malonyl CoA to the terminal thiol of holo acyl carrier protein (ACP).

Malonyl CoA is formed in the first step of mitochondrial fatty acid synthesis (mtFASII) from malonic acid by malonyl CoA synthetase (ACSF3).

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

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.

Malonyl CoA plays a special role in the mitochondrial clearance of toxic malonic acid in the metabolic disorder combined malonic and methylmalonic aciduria (CMAMMA). In CMAMMA due to ACSF3, malonyl CoA synthetase is decreased, which can generate malonyl CoA from malonic acid, which can then be converted to acetyl CoA by malonyl CoA decarboxylase. In contrast, in CMAMMA due to malonyl CoA decarboxylase deficiency, malonyl CoA decarboxylase is decreased, which converts malonyl CoA to acetyl CoA.