Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8384050 | FEBS Letters | 2008 | 8 Pages |
Abstract
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), Î4-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 Î4-valproyl-CoA, at 1Â mM). 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.
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Authors
Cátia C.P. Aires, Graça Soveral, Paula B.M. LuÃs, Herman J. ten Brink, Isabel Tavares de Almeida, Marinus Duran, Ronald J.A. Wanders, Margarida F.B. Silva,