Monks T J, Lau S S
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712.
Adv Pharmacol. 1994;27:183-210. doi: 10.1016/s1054-3589(08)61033-9.
From this and other chapters in this volume, it should be clear that GSH conjugation no longer represents a mechanism for the detoxication of xenobiotics or their metabolites.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).
从本章及本卷中的其他章节可以清楚地看出，谷胱甘肽结合不再是外源性物质或其代谢产物解毒的一种机制。虽然大多数与谷胱甘肽的结合确实有助于外源性物质从体内有效排出，但现在有许多例子表明，这个过程会导致生物活性增强（蒙克斯等人，1990年a；蒙克斯和刘，1992年，1994年）。谷胱甘肽结合在生物活性中间体生成中起重要作用的例子数量正在迅速增加，并且谷胱甘肽依赖性毒性以多种不同方式表现出来。正如本章所强调的，谷胱甘肽可以作为活性代谢产物的转运形式，使这些代谢产物能够输送到初始结合部位远端的靶组织。这种类型的谷胱甘肽结合物可能在多种氧化还原活性化合物的致突变、致癌、肾毒性、胚胎毒性、致白内障、高铁血红蛋白血症和神经毒性特性中起重要作用（蒙克斯和刘，1992年）。
