trans-2-en-valproate and 2-n-propyl-4-pentynoic-acid

The pyruvate uptake rate in inverted submitochondrial vesicles prepared from rat liver was optimized and further characterized; the potential inhibitory effects of the anticonvulsive drug valproic acid or 2-n-propyl-pentanoic acid (VPA), Delta4-valproic acid or 2-n-propyl-4-pentenoic acid and the respective coenzyme A (CoA) conjugates were studied in the presence of a proton gradient. All tested VPA metabolites inhibited the pyruvate uptake, but the CoA esters were stronger inhibitors (40% and 60% inhibition, respectively, for valproyl-CoA and Delta4-valproyl-CoA, at 1mM). At the same concentration, the specific inhibitor 2-cyano-4-hydroxycinnamate decreased the pyruvate uptake rate by 70%. The reported inhibition of the mitochondrial pyruvate uptake may explain the significant impairment of the pyruvate-driven oxidative phosphorylation induced by VPA.

Topics: Animals; Anticonvulsants; Biological Transport; Coenzyme A; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Liver; Male; Mitochondria, Liver; Mitochondrial Membranes; Oxidative Phosphorylation; Pyruvic Acid; Rats; Rats, Wistar; Valproic Acid