Document Detail


Glutathione transferase zeta-catalyzed biotransformation of deuterated dihaloacetic acids.
MedLine Citation:
PMID:  10441501     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glutathione transferase zeta (GSTZ) catalyzes the biotransformation of alpha-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 [(2)H]dichloroacetic acid and [(2)H]chlorofluoroacetic acid as substrates, the deuterium present in the [(2)H]dihaloacetic acid was retained in the [(2)H]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.
Authors:
M F Wempe; W B Anderson; H F Tzeng; P G Board; M W Anders
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  261     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1999 Aug 
Date Detail:
Created Date:  1999-09-09     Completed Date:  1999-09-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  779-83     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Affiliation:
Department of Pharmacology and Physiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York, 14642, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetic Acids / pharmacokinetics*
Animals
Biotransformation
Deuterium*
Dichloroacetate / pharmacokinetics*
Glutathione Transferase / metabolism*
Glyoxylates / metabolism
Half-Life
Humans
Isoenzymes / metabolism*
Rats
Grant Support
ID/Acronym/Agency:
ES03127/ES/NIEHS NIH HHS; ES07026/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Acetic Acids; 0/Glyoxylates; 0/Isoenzymes; 13425-80-4/Dichloroacetate; 298-12-4/glyoxylic acid; 471-44-3/chlorofluoroacetic acid; 7782-39-0/Deuterium; EC 2.5.1.18/Glutathione Transferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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