Evidence for two separate β-ketoacyl CoA reductase components of the hepatic microsomal fatty acid chain elongation system in the rat

The hepatic microsomal fatty acid chain elongation system can utilize either NADPH or NADH. Elongation activity, measured as the rate of malonyl CoA incorporation into palmitoyl CoA, was enhanced by a fat-free diet and by bovine serum albumin (BSA) when either cofactor was employed. When the intermediate products were determined, it was observed that in the presence of BSA and NADPH, the predominant product was the saturated elongated fatty acid, whereas in the presence of BSA and NADH, the major intermediate was the β-ketoacyl derivative. Employing β-ketostearoyl CoA as substrate, BSA markedly inhibited NADH-supported β-ketoacyl CoA reductase activity and stimulated NADPH-supported activity. Furthermore, the sum of the NADH-dependent and NADPH-dependent β-ketoreductase activities approximated the activity obtained when both cofactors were present in the incubation medium, suggesting the existence of two β-ketoacyl CoA reductases, one using NADH and the other NADPH.