On the Mechanism and Control of the Malonyl‐CoA‐Dependent Chain Elongation of Fatty Acids

Abstract

The purification of the microsomal fatty acid chain elongating system from beef adrenal cortex is described. The elongation system requires for optimal activity malonyl‐CoA, ATP, Mg2+, NADPH or NADH. Long‐chain fatty acyl‐CoA derivatives inhibit the incorporation of [1,3‐14C]malonyl‐CoA into fatty acids. Supplementation of the system with enzymes of the C‐3 oxidation sequence allows also an acetyl‐CoA‐dependent chain elongation. Microsomes from beef adrenal cortex contain 2,3‐trans‐hexenoyl‐CoA reductase with similar properties as described for rat liver. The ratio of the specific activities of the hexenoyl‐CoA reductase and chain elongation remains constant in the course of purification from rat liver and beef adrenal cortex. From this finding it is concluded that hexenoyl‐CoA reductase is an integrated part of the microsomal malonyl‐CoA‐dependent chain elongation system. The physiological substrates of hexenoyl‐CoA reductase are 2,3‐unsaturated acyl‐CoA derivatives of polyenoic long‐chain fatty acids with a preference for structures present in γ‐linolenic acid. Competitive inhibition of the microsomal enoyl‐CoA reductase by malonyl‐CoA with respect to enoyl‐CoA suggests that a multienzyme complex is involved in the microsomal chain elongation process. Octenoyl‐CoA, octenoyl‐pantethein and octenyl‐acyl‐carrier protein are substrates of the microsomal hexenoyl‐CoA reductase from rat liver with decreasing maximal velocities and affinities. Octenoyl‐acyl‐carrier protein and malonyl‐CoA are competitive, suggesting identical mechanisms of reduction for octenoyl‐acyl‐carrier protein and octenoyl‐CoA by the multienzyme complex.