Glutathione adduct

Stevens GJ, Hitchcock K, Wang YK, et al. In Vitro metabolism of N-(5-Chloro-2-methylphenyl)-N-(2-methylpropyl)thiourea species comparison and identification of a novel thiocarbamide-glutathione adduct. Chem Res Toxicol 1997 10 733-741. 

When administered orally to rats at various doses, U-91592 was completely absorbed and extensively metabolized [118]. Two metabolites (a phenol glucuronide and a glutathione adduct) were formed following initial cytochrome P450 mediated epoxidation of the heterocycle. The third metabolite was the triester (9.52, Fig. 9.11), which was also a major product of in vitro metabolism in rat liver microsomes. Interestingly, the formation of the tries-... 

Ozawa N, Guengerich FP. 1983. Evidence for formation of an S-[2(N -guanyl]ethyl) glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA. Proc Natl Acad Sci USA 80 5266-5270. 

Reiter R, Burk RF. 1988. Formation of glutathione adducts of carbon tetrachloride metabolites in a rat liver microsomal incubation system. Biochem Pharmacol 37 327-331. 

Curcumin (diferuloylmethane) has very low oral bioavailability, but is rapidly absorbed and low nanomolar levels of the parent compound and its glucuronide and sulfate conjugates can be detected in human plasma and portal circulation after very high (nondietary) intakes (3.6g/day for 1 week). Metabolic reduction occurs in the liver, and glutathione adducts have been observed in vitro ... 

Mycale sp. from Japan contained thiomycalolides A (619) and B (620) as minor metabolites. They are highly cytotoxic glutathione adducts of the known metabolites mycalolides A and B [494]. 

Deterding, L. J., Srinivas, P., Mahmood, N. A., Burka, L. T., and Tomer, K. B. (1989). Fast atom bombardment and tandem mass spectrometry for structure determination of cysteine, N- acety I cyste i n e, and glutathione adducts of xenobiotics. Anal. Biochem. 183 94-107. 

Stevens, G. J. Hitchcock, K. Wang, Y. K. Coppola, G. M. Versace, R. W. Chin, J. A. Shapiro, M. Suwanrumpha, S. Mangold, B. L. 1997. In vitro metabolism of N-(5-chloro-2-methylphenyl)-N -(2-methylpropyl) thiourea species comparison and identification of a novel thiocar-bamide-glutathione adduct. Chem. Res. Toxicol., 10,733-741. 

R R Alkene c=c r R CYP, GST Epoxidation, glutathione adduct formation 0 Amide R-C-NH-R Amidase (esterase)... 

Nocerini MR, Yost GS, Carlson JR, Liberato DJ, Breeze RG (1985) Structure of the glutathione adduct of activated 3-methylindole indicates that an imine methide is the electrophilic intermediate. Dmg Metab Dispos 13 690-694... 

The latter reaction sequence was of importance since addition of the thiol glutathione to arene-oxide intermediates under control of hepatic glutathione-S-epoxide transferase enzyme(s) is a very important metabolic transformation. It would appear probable that most of the structures of the arene oxide-glutathione adducts (premercapturic acids) reported in the literature before 1975 are incorrect with respect to the position of the hydroxy and thioether substituents (they should now be reversed). Addition of thiomethoxide anion to arene oxide 70 may occur via 1,6- and 1,4-addition, although one of these thioether adducts could also be accounted for by the alternative arene-oxide intermediate obtained from an oxygen-walk. Styrene 3,4-oxide (S3) has been observed to react with ethanethiol to yield three adducts which appear to aromatize to three isomeric ethylthiostyrenes without the formation of episulphonium intermediates. ... 

RG Tirona, E Tan, G Meier, KS Pang. Uptake and glutathione conjugation of ethacrynic acid and efflux of the glutathione adduct by periportal and perivenous rat hepatocytes. J Pharmacol Exp Ther 291 1210—1219, 1999. 

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