Acetyl-CoA Carboxylase

Acetyl-CoA carboxylase catalyzes the ATP-dependent carboxylation of acetyl-CoA, a rate-limiting step in fatty acid biosynthesis. Acetyl-CoA carboxylase has crucial roles in fatty acid metabolism and is an attractive target for drug discovery against diabetes, cancer, and other diseases.

In animals, there are two major isoforms of ACCs, ACC1, and ACC2, which are encoded by different genes and display distinct tissue and cellular distribution. The first committed step of fatty acid synthesis (FASyn) is mediated by ACC, which in mammals is encoded by two related enzymes ACC1 and ACC2, which catalyze the ATP-dependent carboxylation of acetyl-CoA to form malonyl-CoA. ACC1 encodes a cytoplasmic isoform that is thought to be the predominant isoform controlling FASyn, whereas ACC2 is tethered to the mitochondrial outer membrane, where localized malonyl-CoA production blocks carnitine palmitoyltransferase-1 (CPT-1) function to prevent fatty acids from entering the mitochondria to undergo fatty acid oxidation (FAOxn).