Biosynthesis of fatty acids: IV. Studies with inhibitors

Abstract

Tetrolyl-CoA and propiolyl-CoA have been shown to be strong noncompetitive inhibitors of fatty acid synthesis. Acrylyl-CoA and isocrotonyl-CoA also inhibit, but much higher concentrations are required. It is suggested that this inhibition occurs through an interaction between the triple and double bonds of these compounds and enzyme sulfhydryl groups. Palmityl-CoA and free CoA have also been shown to inhibit fatty acid synthesis and to block the condensation of acetyl-CoA with malonyl-CoA, and the reduction of crotonyl-CoA to butyrate. The reduction of acetoacetyl-CoA to the β-hydroxy derivative was not inhibited by these materials, although the complete reduction to butyrate was prevented. The addition of flavin nucleotides also inhibited fatty acid synthesis catalyzed by brain enzyme preparations.