Pyruvate uptake is inhibited by valproic acid and metabolites in mitochondrial membranes
| Autor: | Herman J. ten Brink, Paula B.M. Luís, Ronald J.A. Wanders, Isabel Tavares de Almeida, Margarida F. B. Silva, Marinus Duran, C. C. P. Aires, Graça Soveral |
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| Přispěvatelé: | Repositório da Universidade de Lisboa, Other departments, Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases, Clinical chemistry, Neuroscience Campus Amsterdam 2008 |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Pyruvate decarboxylation Biochemistry & Molecular Biology Pyruvate dehydrogenase kinase Coenzyme A Pyruvate transport Biophysics Mitochondria Liver Oxidative phosphorylation Biochemistry Oxidative Phosphorylation Fatty Acids Monounsaturated chemistry.chemical_compound Structural Biology Pyruvic Acid Valproic acid Genetics Animals Inverted submitochondrial membranes Rats Wistar Inner mitochondrial membrane Molecular Biology Drug metabolism Chemistry Biological Transport Cell Biology Rats Pyruvate carboxylase Liver Mitochondrial pyruvate uptake Mitochondrial Membranes Fatty Acids Unsaturated Anticonvulsants lipids (amino acids peptides and proteins) Pyruvic acid Δ4-Valproic acid |
| Zdroj: | FEBS letters, 582(23-24), 3359-3366. Wiley-Blackwell Aires, C C P, Soveral, G, Luis, P B M, ten Brink, H J, Tavares de Almeida, I, Duran, M, Wanders, R J A & Silva, M F B 2008, ' Pyruvate uptake is inhibited by valproic acid and metabolites in mitochondrial membranes ', FEBS Letters, vol. 582, no. 23-24, pp. 3359-3366 . https://doi.org/10.1016/j.febslet.2008.08.028 FEBS Letters, 582(23-24), 3359-3366. Wiley-Blackwell Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/j.febslet.2008.08.028 |
| Popis: | 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), Delta(4)-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 Delta(4)-valproyl-CoA, at 1 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. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.. - Fundacao para a Ciencia e a Tecnologia (FCT) , Lisboa, Portugal [POCTI/FCB/48800/2002]; FEDER ; [SFRH/BD/22420/2005]. - This work was financially supported by Fundacao para a Ciencia e a Tecnologia (FCT), Lisboa, Portugal (POCTI/FCB/48800/2002 with partial funding of FEDER and SFRH/BD/22420/2005). |
| Databáze: | OpenAIRE |
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