Glutathione transferase zeta-catalyzed biotransformation of deuterated dihaloacetic acids

Michael F. Wempe, Wayne B. Anderson, Huey Fen Tzeng, Philip G. Board, M. W. Anders*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    14 Citations (Scopus)

    Abstract

    Glutathione transferase zeta (GSTZ) catalyzes the biotransformation of α-haloalkanoic acids. Treatment of rats or humans with dichloroacetic acid prolongs its elimination half-life, and preliminary studies in this laboratory show that fluorine-lacking, but not fluorine-containing dihaloacetic acids inactivate GSTZ. In the present study, the GSTZ-catalyzed biotransformation of unlabeled and deuterated dihaloacetic acids was investigated. With [2H]dichloroacetic acid and [2H]chlorofluoroacetic acid as substrates, the deuterium present in the [2H]dihaloacetic acid was retained in the [2H]glyoxylic acid formed. This finding indicates that the enol of the dihaloacetic acid does not serve as the substrate for the enzyme. The data afford an explanation of the failure of fluorine-containing dihaloacetic acids to inactivate GSTZ: dichloroacetic acid is converted to glyoxylic acid and inactivates GSTZ, whereas chlorofluoroacetic acid is biotransformed to glyoxylic acid, but produces negligible inactivation. Mechanisms are presented indicating that this difference may be attributed to the nucleofugicity of the leaving group.

    Original languageEnglish
    Pages (from-to)779-783
    Number of pages5
    JournalBiochemical and Biophysical Research Communications
    Volume261
    Issue number3
    DOIs
    Publication statusPublished - 11 Aug 1999

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