Isoforms of acetyl-CoA carboxylase: structures, regulatory properties and metabolic functions.

Acetyl-CoA carboxylase (ACC; EC 6.4.1.2) catalyses the formation of malonyl-CoA, which is essential as a metabolic substrate and as a modulator of specific protein activity. Malonyl-CoA is a substrate for fatty acid synthase (FAS), for polyketide synthases (in plants, fungi and bacteria) and for fatty acyl chain-elongation systems. As an allosteric modulator, malonyl-CoA potently inhibits carnitine palmitoyltransferase-I (CPT-I), with far-reaching effects on intermediary metabolism and cell secretory functions. ACC contributes importantly to flux control in fatty acid biosynthesis and b-oxidation and is subject to a range of interacting mechanisms that dictate tissue-specific expression and specific enzyme activity. Detailed reviews of ACC enzymology appeared in the late 1980s [l-31, so we focus on selected developments since 1990, with most emphasis on the properties of the mammalian multifunctional ACC polypeptides. We discuss the structure and regulation of the ACC genes only briefly, since these aspects are dealt with elsewhere [4].