STUDY OF THE MECHANISM OF INHIBITION OF KETOGENESIS BY PROPIONATE IN BOVINE LIVER

Abstract

Propionate caused an inhibition of ketogenesis from butyrate by bovine liver slices. When succinate, fumarate and aspartate were included in the incubation mixtures as sources of oxaloacetate, they were not as inhibitory as propionate. The possibility of competition between propionate and butyrate for cofactors required for activation was discounted when neither ATP (17 mM), nor carnitine (3.5 mM), added to expand the coenzyme A (CoA) pool, relieved the antiketogenic effect of propionate. The 3-hydroxy-3-methylglutaryl-CoA pathway appeared to be the major route for formation of acetoacetate from acetoacetyl-CoA in liver extracts, on the basis of enzyme assays. At a concentration of 0.5 mM, propionyl-CoA caused an apparent decrease of 3-hydroxy-3-methylglutaryl-CoA synthase activity of 46%, whereas propionate and methylmalonyl-CoA were not effective. At a concentration of 15 mM, propionate resulted in 30% inhibition of synthase activity. Propionyl-CoA did not affect the activity of 3-hydroxy-3-methylglutaryl-CoA lyase. It was suggested that in bovine liver the antiketogenic effect of propionate is achieved, at least in part, through inhibition of formation of acetoacetate from acetoacetyl-CoA.