Glutathione-dependent Bioactivation of Haloalkanes and Haloalkenes

• Published in: Drug metabolism reviews Vol. 36; no. 3-4; pp. 583 - 594
• Main Author: Anders, M. W.
• Format: Journal Article
• Language: English
• Published: New York, NY Informa UK Ltd 01.10.2004; Taylor & Francis; Informa Healthcare
• Subjects: Alkanes - chemistry; Alkanes - metabolism; Alkenes - chemistry; Alkenes - metabolism; Animals; Betalyase; Biological and medical sciences; Biotransformation - physiology; Chemical and industrial products toxicology. Toxic occupational diseases; Glutathione; Glutathione - metabolism; Glutathione transferase; Haloalkanes; Haloalkenes; Humans; Medical sciences; Toxicology; Various organic compounds; Alkene; Toxicity; Haloalkane; Metabolic activation; Pharmacokinetics; Metabolism; Glutathione
• ISSN: 0360-2532; 1097-9883
• DOI: 10.1081/DMR-200033451

Haloalkanes and haloalkenes constitute an important group of widely used chemicals that have the potential to induce toxicity and cancer. The toxicity of haloalkanes and haloalkenes may be associated with cytochromes P450− or glutathione transferase-dependent bioactivation. This review is concerned with the glutathione− and glutathione transferase-dependent bioactivation of dihalomethanes, 1,2-dihaloalkanes, and haloalkenes. Dihalomethanes, e.g., dichloromethane, and 1,2-dihaloethanes, e.g., 1,2-dichloroethane and 1,2-dibromoethane, undergo glutathione transferase-catalyzed bioactivation to give S-(halomethyl)glutathione or glutathione episulfonium ions, respectively, as reactive intermediates. Haloalkenes, e.g., trichloroethene, hexachlorobutadiene, chlorotrifluoroethene, and tetrafluoroethene, undergo cysteine conjugate β-lyase-dependent bioactivation to thioacylating intermediates, including thioacyl halides, thioketenes, and 2,2,3-trihalothiiranes. With all of these compounds, the formation of reactive intermediates is associated with their observed toxicity.