Acetyl-CoA carboxylase 1 and Acetyl-CoA carboxylase 2 (ACC1 and ACC2)

Acetyl-CoA carboxylase 1 and Acetyl-CoA carboxylase 2 are large, multi-domain, biotin-dependent enzymes that catalyze the carboxylation of acetyl-CoA to form malonyl-CoA, the first and regulatory step in fatty acid synthesis. ACC1 is predominantly cytosolic and controls de novo fatty acid biosynthesis, while ACC2 is associated with mitochondria and regulates fatty acid oxidation by producing malonyl-CoA that inhibits carnitine palmitoyltransferase 1. Both are tightly regulated by phosphorylation (notably by AMPK), polymerization, and allosteric modulators, making them attractive and validated therapeutic targets in cancer, metabolic disease, and cardiovascular conditions.

Other names

ACCACCαACCβAcetyl-CoA carboxylase alphaAcetyl-CoA carboxylase beta

Inhibition of ACC1/ACC2 reduces malonyl-CoA production, suppressing de novo fatty acid synthesis. ACC2 inhibition increases mitochondrial fatty acid oxidation by reducing malonyl-CoA inhibition of carnitine palmitoyltransferase 1. Modulation of ACC dimerization and phosphorylation status controls enzymatic activity.