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Browsing by Author "Silva, Margarida F. B."

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  • Mechanisms of valproic acid toxicity
    Publication . Aires, Catia C. P.; van Cruchten, Arno; Ruiter, Jos; Ijist, Lodewijk; de Almeida, Isabel Tavares; Duran, Marinus; Wanders, Ronald J. A.; Silva, Margarida F. B.
    2008Journal article Metadata only Show more
  • Pyruvate uptake is inhibited by valproic acid and metabolites in mitochondrial membranes
    Publication . Aires, Catia C. P.; Soveral, Graca; Luis, Paula B. M.; ten Brink, Herman J.; de Almeida, Isabel Tavares; Duran, Marinus; Wanders, Ronald J. A.; Silva, Margarida F. B.
    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).
    2008Journal article Metadata only Show more
  • Studies on the extra-mitochondrial CoA-ester formation of valproic and Delta(4)-valproic acids
    Publication . Aires, Catia C. P.; Ruiter, Jos P. N.; Luis, Paula B. M.; ten Brink, Herman J.; Ijlst, Lodewijk; de Almeida, Isabel Tavares; Duran, Marinus; Wanders, Ronald J. A.; Silva, Margarida F. B.
    The hypothesis whether valproic acid (VPA) and its main microsomal metabolite, Delta(4) -valproic acid, can be activated to the respective CoA esters in the cell cytosol was investigated. The valproyl-CoA formation was measured in different subcellular fr
    2007Journal article Metadata only Show more
  • Valproic acid metabolites inhibit dihydrolipoyl dehydrogenase activity leading to impaired 2-oxoglutarate-driven oxidative phosphorylation
    Publication . Luis, Paula B. M.; Ruiter, Jos P. N.; Aires, Catia C. P.; Soveral, Graca; de Almelda, Isabel Tavares; Duran, Marinus; Wanders, Ronald J. A.; Silva, Margarida F. B.
    The effect of the antiepileptic drug valproic acid (VPA) on mitochondrial oxidative phosphorylation (OXPHOS) was investigated in vitro. Two experimental approaches were used, in the presence of selected respiratory-chain Substrates: (1) formation of ATP i
    2007Journal article Metadata only Show more