Is fluoroacetate-specific defluorinase a glutathione S-transferase?

Tu, L, Chen, Y, Wright, P, Rix, C and Ahokas, J 2006, 'Is fluoroacetate-specific defluorinase a glutathione S-transferase?', Comparative Biochemistry and Physiology. Part C: Toxicology and Pharmacology, vol. 143, no. 1, pp. 59-66.


Document type: Journal Article
Collection: Journal Articles

Title Is fluoroacetate-specific defluorinase a glutathione S-transferase?
Author(s) Tu, L
Chen, Y
Wright, P
Rix, C
Ahokas, J
Year 2006
Journal name Comparative Biochemistry and Physiology. Part C: Toxicology and Pharmacology
Volume number 143
Issue number 1
Start page 59
End page 66
Total pages 8
Publisher Elsevier Science
Abstract Fluoroacetate-specific defluorinase (FSD) is a critical enzyme in the detoxication of fluoroacetate. This study investigated whether FSD can be classed as a glutathione S-transferase (GST) isoenzyme with a high specificity for fluoroacetate detoxication metabolism. The majority of FSD and GST activity, using 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) as GST substrates, in rat liver was cytosolic. GSTT1 specific substrate, EPNP caused a slight non-competitive inhibition of FSD activity. CDNB, a general substrate of GST isoenzyme, was a more potent non-competitive inhibitor of FSD activity. The fluoroacetate defluorination activity by GST isoenzymes was determined in this study. The results showed that the GSTZ1C had the highest fluoroacetate defluorination activity of the various GST isoenzymes studied, while GSTA2 had a limited activity toward fluoroacetate. The human GSTZ1C recombinant protein then was purified from a human GSTZ1C cDNA clone. Our experiments showed that GSTZ1C catalysed fluoroacetate defluorination. GSTZ1 shares many of the characteristics of FSD; however, it accounts only for 3% of the total cytosolic FSD activity. GSTZ1C based enzyme kinetic studies has low affinity for fluoroacetate. The evidence suggests that GSTZ1 may not be the major enzyme defluorinating fluoroacetate, but it does detoxify the fluoroacetate. To clarify the identity of enzymes responsible for fluoroacetate detoxication, further studies of the overall FSD activity are needed.
Subject Toxicology (incl. Clinical Toxicology)
Keyword(s) Mouse-Liver Cytosol
Dichloroacetic Acid
Rat
Zeta
Metabolism
Biotransformation
Purification
Resistance
Mammals
DOI - identifier 10.1016/j.cbpc.2005.12.003
Copyright notice Copyright © 2005 Elsevier Inc. All rights reserved.
ISSN 1532-0456
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