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 language | English |
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Pages (from-to) | 779-783 |
Number of pages | 5 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 261 |
Issue number | 3 |
DOIs | |
Publication status | Published - 11 Aug 1999 |