Acetyl-coa carboxylase

Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that plays a crucial role in fatty acid metabolism. It catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, a critical step in the biosynthesis of long-chain fatty acids.

Structure

ACC is a multi-subunit enzyme in most prokaryotes and in the chloroplasts of most plants and algae. In animals, ACC is a large, homodimeric protein. The enzyme has two main domains: the biotin carboxylase (BC) domain and the carboxyltransferase (CT) domain. The BC domain is involved in the ATP-dependent carboxylation of the coenzyme biotin, while the CT domain transfers the carboxyl group from carboxylated biotin to acetyl-CoA.

Function

The primary function of ACC is to provide the malonyl-CoA substrate for the biosynthesis of fatty acids. The product of ACC, malonyl-CoA, is the two-carbon donor in the growing fatty acid chain. In addition to its role in fatty acid synthesis, malonyl-CoA is also a key regulator of fatty acid oxidation.

Regulation

ACC activity is primarily regulated by the allosteric effectors citrate and palmitoyl-CoA. Citrate activates ACC, while palmitoyl-CoA, the product of fatty acid synthesis, inhibits it. ACC is also regulated by covalent modification: in animals and yeast, ACC is inactivated by phosphorylation, and in bacteria and plants, ACC is regulated by a small protein called acetyl-CoA carboxylase carboxylase.

Clinical significance

Alterations in ACC activity and expression have been observed in several human diseases, including type 2 diabetes, cancer, and obesity. Therefore, ACC is considered a potential target for therapeutic interventions.

See also

• Fatty acid synthesis
• Biotin
• Enzyme