REGULATION OF MAMMALIAN ACETYL-COENZYME A CARBOXYLASE

Long-chain fatty acids are involved in all aspects of cellular structure and function. For controlling amounts of fatty acids, cells are endowed with two acetyl-coenzyme A carboxylase (ACC) systems. ACC-α is the rate-limiting enzyme in the biogenesis of long-chain fatty acids, and ACC-β is believed to control mitochondrial fatty acid oxidation. These two isoforms of ACC control the amount of fatty acids in the cells. Phosphorylation and dephosphorylation of ACC-α cause enzyme inactivation and activation, respectively, and serve as the enzyme's short-term regulatory mechanism. Covalently modified enzymes become more sensitive toward cellular metabolites. In addition, many hormones and nutrients affect gene expression. The gene products formed are heterogeneous and tissue specific. The ACC-β gene is located on human chromosome 12; the cDNA for this gene has just been cloned. The gene for the α-isoform is located on human chromosome 17. The catalytic core of the β-isoform is homologous to that of the α-isoform, except for an additional peptide of about 150 amino acids at the N terminus. This extra peptide sequence makes the β-form about 10,000 daltons larger, and it is thought to be involved in the unique role that has been assigned to this enzyme. The detailed control mechanisms for the β-isoform are not known.