Effect of 4‐Pentenoic Acid on Intermediate Metabolism of Tetrahymena*

Abstract

The growth of T. pyriformis strain HSM was strongly inhibited by 4-pentenoic acid. Supplementing the medium with acetate reversed the growth inhibition, but pyruvate was ineffective. Glycogen content was much lower in cells grown with 4-pentenoic acid than in controls; this effect was not reversed by acetate or by pyruvate. There was little effect of 4-pentenoic acid on the incorporation of label from [1-14C]acetate, [2-14C]glycerol, [1-14C]ribose, [U-14C]fructose, or [1-14C]glucose into CO2, but incorporation of label into glycogen was inhibited, the strongest inhibition being on acetate and the weakest (.apprx. 20%) on ribose, fructose and glucose. A 3-compartment model for quantitation of labeled acetyl CoA fluxes was applicable to Tetrahymena grown in the presence of 4-pentenoic acid, and experiments were performed to establish the flux of [1-14C]acetyl CoA into glycogen, lipids, CO2, glutamate and alanine. 4-Pentenoic acid did not appreciably inhibit .beta.-oxidation or lipogenesis, but markedly decreased the glyconeogenic flux of labeled acetyl-CoA from the peroxisomal and outer mitochondrial compartments. At least 2 mechanisms are proposed for the action of 4-pentenoic acid: reduction of the levels of acetyl CoA or free CoA and direct inhibition of enzymes by 4-pentenoyl CoA or its metabolites. Although 4-pentenoic acid has little effect on acetyl-CoA metabolism in the inner mitochondrial compartment, probably the flux through the outer mitochondrial compartment of acetyl-CoA derived from pyruvate is inhibited largely by the 1st, and the glyconeogenic flux of acetyl-CoA is inhibited largely by the 2nd mechanism.