The inhibition of the fatty acid synthetase multienzyme complex of yeast by long-chain acyl coenzyme A compounds.

Abstract

Fatty acid synthetase of yeast was strongly inhibited in vitro by long‐chain acyl coenzyme A thioesters. Increasing the serum albumin concentration in the reaction mixture lowered, but did not prevent, this inhibition. Enzyme kinetic experiments showed that all long‐chain acyl CoA compounds tested were competitive inhibitors of the substrate malonyl CoA. The inhibition with respect to the substrate acetyl CoA and NADPH was non‐competitive. These results support the hypothesis put forth earlier that the end products of the fatty acid synthetase are bound preferentially in the region of the thiol group which is part of the acyl‐carrier‐protein portion of the complex. The data indicate that the long‐chain acyl CoA thioesters may be of importance in the regulation of de novo fatty acid biosynthesis via end product inhibition of the synthetase.