The inactivation of methionine synthase in isolated rat hepatocytes by sodium nitroprusside

Anna Nicolaou, Catherine J. Waterfield, Susan H. Kenyon, William A. Gibbons

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Methionine synthase, the enzyme that catalyses the transfer of a methyl group from 5-methyl tetrahydrofolate to homocysteine via the cofactor methylcobalamin, is one of the two established mammalian enzymes that utilise a biologically active vitamin B-12 derivative. Through its substrates, products and downstream metabolites, methionine synthase is directly involved in the sulphur amino acid pathways, polyamine biosynthesis, biological methylations and one-carbon-unit transfers. Rat liver methionine synthase was shown to be inactivated by the nitric oxide donor sodium nitroprusside. The inactivation occurred during the treatment of isolated rat hepatocytes in a time-dependent and dose-dependent manner with an apparent IC50 value of 170 μM. Highly purified rat liver methionine synthase was inactivated in a partially irreversible manner with an apparent IC50 value of 10 μM. The inactivation has been attributed to nitric oxide released by sodium nitroprusside. Since biomolecules possessing transition state metals are targets for nitric oxide, the possibility of a nitric oxide-cobalamin interaction could explain the observed inactivation. Nitric oxide is directly involved in different aspects of liver metabolic functions both under physiological and pathological conditions like sepsis and inflammation. The nitric-oxide-induced inactivation of methionine synthase could offer a rational explanation for the cellular and cytotoxic effects of this highly reactive molecule.
    Original languageEnglish
    Pages (from-to)876-882
    Number of pages6
    JournalEuropean Journal of Biochemistry
    Volume244
    Issue number3
    Publication statusPublished - 1997

    Keywords

    • Hepatocytes
    • Homocysteine
    • Methionine synthase
    • Nitric oxide
    • Sodium nitroprusside

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