MalonylCoAn

Malonyl-CoA (malonyl-Coenzyme A) is the coenzyme A thioester of malonic acid. In biochemistry, it functions as a two-carbon donor in lipid biosynthesis and as a regulatory metabolite. Its principal role is in fatty acid synthesis, where it supplies two-carbon units for chain elongation by fatty acid synthase. In most cells, malonyl-CoA is generated from acetyl-CoA by acetyl-CoA carboxylase (ACC), a biotin-dependent enzyme that uses CO2 and ATP. Depending on organism, ACC exists in cytosolic or mitochondrial forms and is tightly regulated by phosphorylation, allosteric effectors such as citrate and fatty acyl-CoAs, and hormonal signals.

Pathways: In the fatty acid synthase cycle, malonyl-CoA can be converted to malonyl-ACP (acyl carrier protein) or transferred to acetyl groups by other enzymes; in bacteria and plants, malonyl-CoA is commonly used by type II FAS or by polyketide synthases as an extender unit to build polyketide chains.

Regulation and metabolic control: Malonyl-CoA also inhibits carnitine palmitoyltransferase I (CPT1) at the outer mitochondrial membrane, reducing mitochondrial fatty acid import and beta-oxidation when lipid synthesis is active. Malonyl-CoA decarboxylase can lower malonyl-CoA levels, relieving inhibition of beta-oxidation.

Locations and significance: It is present in bacteria, archaea, plants, and animals, and is a key intermediate bridging carbohydrate and lipid metabolism. Because of its central role, malonyl-CoA is a focus of metabolic studies and is implicated in the regulation of metabolism and the biosynthesis of fatty acids and polyketides.