Triacetic acid lactone, a derailment product of fatty acid biosynthesis.

Abstract

If no NADPH is available for reduction, fatty acid biosynthesis is blocked at the stage of the acetoacetyl‐acyl carrier protein intermediate. In this case highly purified fatty acid synthetase from baker's yeast catalyzes, in a derailment reaction, the formation of triacetic acid lactone from acetyl‐ and malonyl‐CoA. The identity of the product was shown by the enzymatic incorporation of radioactivity from [1‐14C]acetyl‐CoA and from recrystallization to constant specific radioactivity. In paper chromatography, thin layer chromatography, and ionophoresis both the chemically synthesized triacetic acid lactone and the enzymatically formed compound migrated with the same RF‐values and electrophoretic mobility. By an oxidation with chromic acid according to the procedure of Kuhn‐Roth it could be demonstrated that the radioactivity of [1‐14C]acetyl‐CoA is incorporated only into the C‐6 position of triacetic acid lactone. Free triacetic acid and tetraacetic acid lactone do not seem to be formed by fatty acid synthetase. The ratio of the malonyl‐CoA utilization for the synthesis of palmitoyl‐ and stearoyl‐CoA to that for the synthesis of triacetic acid lactone was found to be about 90:1. The significance of these findings is discussed. A chemical mechanism for the formation of triacetic acid lactone by fatty acid synthetase is proposed.