Nitric oxide sensitivity of the aconitases

Paul R. Gardner, Giuseppina Costantino, Csaba Szabó, Andrew L. Salzman

    Research output: Contribution to journalArticle

    188 Scopus citations

    Abstract

    Aconitases are important cellular targets of nitric oxide (NO) toxicity, and NO-derived species, rather than NO per se, have been proposed to mediate their inactivation. NO-mediated inactivation of the Escherichia coli aconitase and the porcine mitochondrial aconitase was investigated. In E. coli, aconitase activity decreased by ~70% during a 2-h exposure to an atmosphere containing 120 ppm NO in N2. The NO-inactivated aconitase reactivated poorly in E. coli under anaerobic or aerobic conditions. Elevated superoxide dismutase activity did not affect the aerobic inactivation of aconitase by NO, thus indicating a limited role of the NO'- and superoxide- derived species peroxynitrite. Glutathione-deficient and glutathione- containing E. coli were comparably sensitive to NO-mediated aconitase inactivation, thus excluding the participation of S-nitrosoglutathione or more oxidizing NO-derived species. NO' progressively decreased aconitase activity in extracts in the presence of substrates, and inactivation was greatest at an acidic pH with cis-aconitate. The porcine mitochondrial aconitase was sensitive to NO when exposed at pH 6.5, but not at pH 7.5, and irreversible inactivation occurred during catalysis. The requirement of an acidic pH or substrates for sensitivity may explain the reported resistance of aconitases to NO in vitro (Castro, L., Rodriguez, M., and Radi, R. (1994) J. Biol. Chem. 269, 29409-29415; Hausladen, A., and Fridovich, I. (1994) J. Biol. Chem. 269, 29405-29408). An S-nitrosation of the aconitase [4Fe-4S] center catalyzed by the solvent-exposed electron withdrawing iron atom (Fe(a)) is proposed.

    Original languageEnglish (US)
    Pages (from-to)25071-25076
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume272
    Issue number40
    DOIs
    StatePublished - Oct 3 1997

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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  • Cite this

    Gardner, P. R., Costantino, G., Szabó, C., & Salzman, A. L. (1997). Nitric oxide sensitivity of the aconitases. Journal of Biological Chemistry, 272(40), 25071-25076. https://doi.org/10.1074/jbc.272.40.25071