毒理学相关资料,第四章内容参考文献22.pdfVIP

Chemico-Biological Interactions 129 (2000) 61–76 locatechembiont Glutathione conjugation as a bioactivation reaction Peter J. van Bladeren TNO Nutrition and Food Research and TNO WU Centre for Food Toxicology, PO Box 360, Zeist 3700AJ, The Netherlands Abstract In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate beta-lyase, conjugates that are activated through redox cycling and lastly conjugates that release the original reactive parent compound. The glutathione S-transferases have three connections with the formation of biactivated conju- gates: they catalyze their formation in a number of cases, they are the earliest available target for covalent binding by these conjugates and lastly, the parent alkylating agents are regularly involved in the induction of the enzymes. Individual susceptibility for each of these agents is determined by individual transferase subunit composition and methods are becoming avail- able to assess this susceptibility. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Glutathione S-transferases; Glutathione conjugates; Bioactivation 1. Introduction The glutathione S-transferases are an extremely well studied family of enzymes. The reason no doubt is the dichotomy that on the one hand they seem to fulfill very important functions and are certainly ubiquitous, but that on the other hand man and