malonyylCoAn

Malonyl-CoA is the coenzyme A thioester of malonic acid and a key metabolite in lipid metabolism. It serves as a two-carbon donor unit in de novo fatty acid synthesis and also participates in polyketide biosynthesis in certain organisms. In mammals, it plays a regulatory role by linking energy status to fatty acid oxidation.

Malonyl-CoA is produced by acetyl-CoA carboxylase (ACC) through an ATP- and biotin-dependent carboxylation of acetyl-CoA with carbon dioxide. In vertebrates, two main ACC isoforms exist: ACC1 (predominantly cytosolic and involved in fatty acid synthesis) and ACC2 (associated with the outer mitochondrial membrane and regulation of fatty acid oxidation). In plants, plastidial ACC contributes to fatty acid production and related metabolic processes.

Metabolic roles include its function as the initial substrate for fatty acid synthase during lipogenesis. Additionally, malonyl-CoA inhibits carnitine palmitoyltransferase I (CPT1), reducing the transport of long-chain fatty acids into mitochondria for β-oxidation and thereby linking lipid synthesis to energy balance. Its levels are modulated by citrate (activator) and phosphorylation by AMP-activated protein kinase (inhibitor), reflecting cellular energy and nutrient status.

Beyond metabolism, malonyl-CoA serves as a donor substrate for protein lysine malonylation, a post-translational modification that can affect enzyme activity and cellular signaling. In microbes and plants, malonyl-CoA-derived products include various polyketides with ecological and pharmaceutical significance.