Structure and regulation of rat long-chain acyl-CoA synthetase.

Complementary DNAs encoding rat long-chain acyl-CoA synthetase have been isolated. The cDNAs were identified using synthetic oligonucleotide probes based on partial amino acid sequences of lysyl endopeptidase peptides of the purified enzyme. Rat long-chain acyl-CoA synthetase is predicted to contain 699 amino acid residues and to have a calculated molecular weight of 78,177. Significant sequence similarity was found between parts of long-chain acyl-CoA synthetase and firefly luciferase. Based on the similarity of the reaction mechanisms of the two enzymes, we propose a function for the similar region. The long-chain acyl-CoA synthetase mRNA is expressed in liver, heart, and epididymal adipose tissues and, to a much lesser extent, in brain, small intestine, and lung. The level of long-chain acyl-CoA synthetase mRNA is increased 7-8-fold in rat liver by feeding a diet high in carbohydrate or fat, consistent with the physiological significance of the enzyme in fatty acid metabolism.