Glutathione conjugates metabolite identification

Tang W, Steams RA, Bandiera SM, Zhang Y, Raab C, Braun MP, Dean DC, Pang J, Leung KH, Doss GA, Strauss JR, Kwei GY, Rushmore TH, Chiu SH, Baillie TA. Studies on cytochrome P-450-mediated bioactivation of diclofenac in rats and in human hepatocytes Identification of glutathione conjugated metabolites. Dmg Metab Dispos 1999 27(3) 365-372. 

Figure 9. Identification of metabolites A through D in urine of rats treated with CDA led to the proposed hidden metabolites shown here in brackets. The reactive sulfate conjugate apparently undergoes glutathione conjugation, further metabolism via the mercapturic acid pathway and, finally, C-S cleavage, methylation and sulfur oxidation of C to yield D.

Methyl sulfones are ultimate mammalian metabolites of PCBs produced by a series of reactions involving arene oxides and glutathione conjugates and have been synthesized to enable their conclusive identification and quantification (Bergman and Wach-meister 1978 Haraguchi et al. 1987). This is discussed further in Section 7.5.2. 

Metabolites of the herbicides alachlor and metolachlor in which the chlorine of the -CO. CH2-C1 group is replaced by -S03- by glutathione conjugation and oxidation have been recovered from a number of water courses in the United States Two aspects are worth noting (a) the analytical problems of identification and (b) the fact that the sulfonate of alachlor has low bioconcentration potential and is nonmutagenic in contrast to its precursor (Field and Thurman 1996). 

Kassahun K, Davis M, Hu P, Martin B, BaUhe T. Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat identification of phase 1 metabolites and glutathione conjugates. Chem Res Toxicol 1997 10 1228-1233. 

MR Davis, K Kassahun, CM Jochheim, KM Brandt, TA Baillie. Glutathione and A-acetylcysteine conjugates of 2-chloroethyl isocyanate. Identification as metabolites of N,N -bis(2-chloroethyl)-A-nitrosourea in the rat and inhibitory properties toward glutathione reductase in vitro. Chem Res Toxicol 6 376, 1993. 

K Kassahun, K Farrell, F Abbott. Identification of characterization of the glutathione and N-acetylcysteine conjugates of (E)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid, in rats and humans. Drug Metab Dispos 19 525, 1991. 

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