Glutathione conjugation as a bioactivation reaction.
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 conjugates: 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 available to assess this susceptibility.
van Bladeren
P J
PJ
TNO Nutrition and Food Research and TNO WU Centre for Food Toxicology, PO Box 360, Zeist 3700AJ, The Netherlands. bladeren@voeding.tno.nl
D000818:Animals; D001711:Biotransformation; D013437:Carbon-Sulfur Lyases / Q000378:metabolism; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D010084:Oxidation-Reduction; D015262:Xenobiotics / Q000493:pharmacokinetics* / Q000494:pharmacology
D015262:Xenobiotics; D005982:Glutathione Transferase; D013437:Carbon-Sulfur Lyases; C019969:S-alkylcysteine lyase; D005978:Glutathione