Structure, Mechanism, and Disease Implications of Acetyl CoA Carboxylase: A Mini-review

The ubiquitous acetyl-CoA carboxylase is a pivotal enzyme in the synthesis of fatty acids in both eukaryotes and prokaryotes. The importance of this enzyme is needed in the initiating reaction for synthesizing fatty acids, which are very important when used as fuel molecules and providing the building blocks of biological membranes. Acetyl-CoA carboxylase catalyzes the committed step in making fatty acids by converting acetyl-CoA into malonyl-CoA. With its three functional domains it is a key regulatory enzyme for fatty acid metabolism and its product is key in regulating fatty acid degradation. Its multidomain enzymatic functions are characterized by a biotin carboxylating activity, biotin binding, and a carboxyltransferase activity. At the basic research level, the crystal structures of each of these domains have been determined, and the molecular basis for acetyl-CoA carboxylase inhibition by small molecules is beginning to be understood. Although not much on a deficiency of the enzyme has been reported, there are some cases in which some combinations of the four known human caboxylating enzymes act collectively producing devastating symptoms in neonates and infants.