Glutathione conjugation as a mechanism for the transport of reactive metabolites.

From this and other chapters in this volume, it should be clear that GSH conjugation no longer represents a mechanism for the detoxication of xenobiotics or their metabolites. Although the majority of conjugations with GSH do facilitate the efficient excretion of xenobiotics from the body, many examples now exist where this process results in enhanced biological reactivity (Monks et al., 1990a; Monks and Lau, 1992, 1994). The number of examples in which GSH conjugation plays an important role in the generation of biologically reactive intermediates is expanding rapidly and GSH-dependent toxicity is manifested in many diverse ways. As emphasized in this chapter, GSH can act as a transport form for reactive metabolites, permitting the delivery of such metabolites to target tissues distal to the site of the initial conjugation. This type of GSH conjugate may be important in the mutagenic, carcinogenic, nephrotoxic, embryotoxic, cataractogenic, methemoglobinemic, and neurotoxic properties of a variety of redox active compounds (Monks and Lau, 1992).