malonyl-Coenzyme A

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

== Biosynthesis == Malonyl-CoA cannot freely cross membranes and there is no known malonyl-CoA import mechanism. The biosynthesis therefore takes place locally: cytosol: Malonyl-CoA is formed by carboxylating acetyl-CoA using the highly regulated enzyme acetyl-CoA carboxylase 1 (ACC1). One molecule of acetyl-CoA joins with a molecule of bicarbonate, requiring energy rendered from ATP. Mitochondrial outer membrane: Malonyl-CoA is formed by carboxylating acetyl-CoA using the highly regulated enzyme acetyl-CoA carboxylase 2 (ACC2). The reaction is the same as with ACC1. mitochondrial matrix: Malonyl-CoA is formed in coordinated fashion by mtACC1, a mitochondrial isoform of ACC1, and acyl-CoA synthetase family member 3 (ACSF3), a mitochondrial malonyl-CoA synthetase. MtACC1, like cytosolic ACC1 catalyses the carboxylation of acetyl-CoA, while ACSF3 catalyses the thioesterification of malonate to coenzyme A. The latter serves for the clearance of mitochondrial malonate, since malonate is a potent inhibitor of mitochondrial respiration as it competitively inhibits succinate dehydrogenase. However, the source of malonyl-CoA in the mitochondria is still up for debate.