Glutathione conjugates

FIGURE 2.14 Phase 2 biotransformation—conjugation. (1) Glucuronide formation. (2) Sulfate formation. (3) Glutathione conjugation. 

Residues of PCBs in animal tissues include not only the original congeners themselves, but also hydroxy metabolites that bind to cellular proteins, for example, transthyretin (TTR Klasson-Wehler et al. 1992 Brouwer et al. 1990 Fans et al. 1993). Small residues are also found of methyl-sulfonyl metabolites of certain PCBs (Bakke et al. 1982, 1983). These appear to originate from the formation of glutathione conjugates of primary epoxide metabolites, thus providing further evidence of the existence of epoxide intermediates. Further biotransformation, including methylation, yields methyl-sulfonyl products that are relatively nonpolar and persistent. 

In terrestrial animals, the excreted products of PAHs are mainly conjugates formed from oxidative metabolites. These include glutathione conjugates of epoxides, and sulfate and glucuronide conjugates of phenols and diols. 

Oakley AJ, Lo Bello M, Mazzetti AP, Federici G, Parker MW. The glutathione conjugate of ethacrynic acid can bind to human pi class glutathione transferase Pl-1 in two different modes. FEES Lett 1997 419 32-6. 

Dekant W, Koob M, Henschler D. 1990. Metabolism of trichloroethene—vivo and in vitro evidence for activation by glutathione conjugation. Chem Biol Interact 73 89-101. 

Elfarra AA, Anders MW. 1984. Renal processing of glutathione conjugates. Role in nephrotoxicity. Biochem Pharmacol 33 3729-3732. 

Iverson, S. L. Shen, L. Anlar, N. Bolton, J. L. Bioactivation of estrone and its catechol metabolites to quinoid-glutathione conjugates in rat liver microsomes. Chem. Res. Toxicol. 1996, 9, 492-A99. 

Glucuronidation Sulfation Acetylation Peptide conjugation Glutathione conjugation... 

Suzuki, H., Sugiyama, Y., Excretion of GSSG and glutathione conjugates mediated by MRP1 and cMOAT/ MRP2, Semin. Liver Dis. 1998, 18, 359-376. 

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