title: Biosynthesis of toxic glutathione conjugates from halogenated alkenes.
abstract: Glutathione conjugation has been identified as an important detoxication reaction. However, several glutathione-dependent bioactivation reactions have been identified. Current knowledge on the mechanisms and the possible biological importance of these reactions is discussed in this article. Several polychlorinated alkenes are bioactivated in a complex, glutathione-dependent pathway. The first step is hepatic glutathione S-conjugate formation followed by cleavage to the corresponding cysteine S-conjugates, and, after translocation to the kidney, metabolism by renal cysteine conjugate beta-lyase. Beta-lyase-dependent metabolism of halovinyl cysteine S-conjugates yields electrophilic thioketenes, whose covalent binding to cellular macromolecules is likely responsible for the observed nephrotoxicity of the parent compounds.
authors.affiliation: Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. dekant@toxi.uni-wuerzburg.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dekant
mesh_terms: D000475:Alkenes / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*
chemical_list: D000475:Alkenes; D006846:Hydrocarbons, Halogenated; D005978:Glutathione