Structure and regulation of acetyl-CoA carboxylase genes of metazoa

Acetyl-CoA carboxylase (ACC) plays a fundamental role in fatty acid metabolism. The reaction product, malonyl-CoA, is both an intermediate in the de novo synthesis of long-chain fatty acids and also a substrate for distinct fatty acyl-CoA elongation enzymes. In metazoans, which have evolved energy storage tissues to fuel locomotion and to survive periods of starvation, energy charge sensing at the level of the individual cell plays a role in fuel selection and metabolic orchestration between tissues. In mammals, and probably other metazoans, ACC forms a component of an energy sensor with malonyl-CoA, acting as a signal to reciprocally control the mitochondrial transport step of long-chain fatty acid oxidation through the inhibition of carnitine palmitoyltransferase I (CPT I). To reflect this pivotal role in cell function, ACC is subject to complex regulation. Higher metazoan evolution is associated with the duplication of an ancestral ACC gene, and with organismal complexity, there is an increasing diversity of transcripts from the ACC paralogues with the potential for the existence of several isozymes. This review focuses on the structure of ACC genes and the putative individual roles of their gene products in fatty acid metabolism, taking an evolutionary viewpoint provided by data in genome databases.