MalonüülCoA

MalonüülCoA, commonly written malonyl-CoA, is the CoA thioester of malonic acid. It is a central metabolic intermediate formed by the carboxylation of acetyl-CoA and serves as a key extender unit in fatty acid biosynthesis as well as a regulator of fatty acid oxidation. The reaction is catalyzed by acetyl-CoA carboxylase, a biotin-dependent enzyme, which adds a carboxyl group to acetyl-CoA in the presence of CO2.

In most cells, malonüülCoA provides the two-carbon units that are incorporated into growing fatty acid chains by the fatty acid synthase complex. During the cycle, malonüül units are condensed with acetyl- or longer acyl- groups, with simultaneous decarboxylation, to extend the fatty acid chain by two carbons per cycle. This process ultimately produces saturated long-chain fatty acids, such as palmitate, using NADPH as a reducing agent.

Regulation of malonüülCoA links lipid synthesis to cellular energy status. MalonüülCoA inhibits carnitine palmitoyltransferase I (CPT1), reducing transport of fatty acids into mitochondria for beta-oxidation when synthesis is prioritized. Acetyl-CoA carboxylase activity, and thus malonüülCoA levels, are controlled by hormones and energy signals: citrate activates ACC, while phosphorylation by AMPK and related kinases inhibits ACC. Insulin promotes ACC activation, whereas glucagon and epinephrine shift metabolism toward oxidation.

Distribution and significance extend beyond mammals: malonüülCoA participates in polyketide biosynthesis in bacteria and plants. Clinically, malonüülCoA metabolism can be disrupted in rare disorders, such as malonyl-CoA decarboxylase deficiency, which elevates malonyl-CoA and impairs fatty acid oxidation.