Acetyl-CoA carboxylase enzyme (ACC)

Acetyl-CoA carboxylase enzyme (ACC) is a biotin-dependent enzyme that catalyzes the rate-limiting carboxylation of acetyl-CoA to form malonyl-CoA, the committed step in de novo fatty acid biosynthesis[1][2][4][5][6]. In mammals, two isoforms exist: ACC1 (cytosolic, encoded by ACACA, involved in fatty acid synthesis) and ACC2 (mitochondrial membrane-associated, encoded by ACACB, regulates fatty acid oxidation by producing malonyl-CoA, an inhibitor of carnitine palmitoyltransferase I)[1][2][5]. The enzyme is a multi-domain protein (in eukaryotes), carrying out sequential reactions via its biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase domains[1][2][3]. ACC activity is regulated by phosphorylation, allosteric regulators, hormones, and small molecule inhibitors[3][5]. Its central role in lipid metabolism makes it a promising drug target for cancer, obesity, diabetes, and cardiovascular/metabolic diseases, and a target for antibiotics when selective for bacterial ACC[2][3][5][6].

Other names

Acetyl-CoA carboxylaseACCAcetyl-Coenzyme A carboxylaseAcetyl-CoA carboxylase alpha (ACC1, encoded by ACACA)Acetyl-CoA carboxylase beta (ACC2, encoded by ACACB)

Inhibition of ACC catalytic activity, either at the biotin carboxylase (BC) domain or carboxyltransferase (CT) domain, reducing malonyl-CoA production, thus impairing fatty acid biosynthesis and, in ACC2 case, increasing fatty acid oxidation[3][5][6].