GSH S-transferase

Figure 53-1. Simplified scheme showing how metabolism of a xenobiotic can result in cell injury, immunologic damage, or cancer. In this instance, the conversion of the xenobiotic to a reactive metabolite is catalyzed by a cytochrome P450,and the conversion of the reactive metabolite (eg, an epoxide) to a nontoxic metabolite is catalyzed either by a GSH S-transferase or by epoxide hydrolase.

Fair, P.H. 1986. Interaction of benzo[a]pyrene and cadmium on GSH-S-transferase and benzo[a]pyrene hydroxylase in the black sea bass Centropristis striata. Arch. Environ. Contam. Toxicol. 15 257-263. 

Ivanetich KM, Thumser AE, A. 1987. Reversible inhibition and activation of hepatic GSH S-transferases by ethylene dibromide. Pharmac Ther 33 85,88. 

Ivanetich KM, Ziman MR, Mennie REM, et al. 1984. Inhibition of rat GSH S-transferases by ethylene dibromide. Res Common Chem Pathol Pharmacol 45 233-242. 

In in vitro studies with 10 plant species, all 10 species contained GSH S-transferases that utilized PCNB as a substrate (.5). 

Lam, L. K. T., V. L. Spamins, and L. W. Wattenberg. Isolation and identification of kahweol palmitate and cafestol palmitate as active constituents of green coffee beans that enhance glutathione (GSH) S-transferase activity. Proc Am Ass Cancer Res 1982 23 88. 

Glutathione conjugation Glutathione (GSH) GSH-S-transferase (cytosol, microsomes) Epoxides, arene oxides, nitro groups, hydroxylamines Acetaminophen, ethacrynic acid, bromobenzene... 

The mechanism seems to involve first the formation of a GSH conjugate in the liver, catalyzed by the microsomal GSH S-transferase. The hepatic metabolite is then secreted into... 

Table VI. Effect of Dietary Vitamin E and Cigarette Smoking on GSH S-Transferase Activity ...

Considerable interest was generated when it was shown that substantial GSHPx activity exists in liver of selenium-depleted rats when LOOH is used as substrate but not H2O2 [20]. The enzyme was subsequently shown to be identical to a member of the glutathione-S-transferase family of enzymes [20,21,48], The enzyme was for a time called selenium-independent , or non-selenium dependent GSHPx and this nomenclature, which is confusing, has persisted in the literature. The role of GSH-S-transferases in the overall protection of cells against the harmful potential of LOOH has not been determined but it undoubtedly must form part of that protective mechanism. 

CDAA also elevated GSH-S -transferase activity in corn roots or shoots (Table VI) when assayed spectrophotometrical ly with CDNB (l-chloro-2,4-dinitrobenzene) (20). However, in this case, treatment with CDAA for 2.5 days produced the greatest increase in enzyme activity in the roots of 6-day-old corn seedlings. 

Table VI. Effect of CDAA pretreatments on GSH-S.-transferase activity in roots or shoots of 6-day-old corn seedlings (c.v. PAG SX-111).

Although CDAA pretreatments elevated both GSH and GSH-S.-transferase activity (as assayed by CDNB), it was essential to determine whether these effects would actually result in greater CDAA metabolism. For these studies, we examined [14C]CDAA metabolism in vitro and in excised corn root tips [detailed methods described by Ezra et. al. (20)]. The in vitro assay revealed a significant level of non-enzymatic [A C] CDAA... 

The effects of R-25788 on elevation of GSH and GSH-S.-transferase have been well documented (13). However, unlike CDAA, R-25788 pretreatments did not prevent or reduce injury to corn seedlings from later higher doses of R-25788 (Figure 6). 

Dihydroxy-9,10-cpoxy-beny.pyrene, as well as other epoxide compounds, can be detoxified by glutathione. A number of different GSH S-transferases can catalyze the transfer of GSH to the epoxide. This transfer results in the formation of a GSH conjugate. An example of the reaction is shown in Figure 10.64. The resulting conjugate is not carcinogenic. It can be readily excreted in the bile. 

CPH-treatment of rats (1200 mg/kg/d for 2 d) induced the enzymatic activities of other renal cortical drug-metabolizing enzymes such as 7-ethoxy-couma-rine-O-deethylase and cytosolic GSH-S-transferase whereas the enzymatic activities of aniline hydroxylase and aminopyrine-N-demethylase were simultaneously decreased or remained unchanged, respectively (Table 1) [74]. Treatment of male and female rats with cephaloridine (750 mg/kg/d) for two weeks to three... 

A few fine points concerning GSH S-transferase might be of interest. There is evidence that a large proportion of the population lacks one of the GSH S-trans-... 

The glutathione (L-y-glutamyl-L-cysteinylglycine GSH) S-transferases (GSTs) are a multigene family of dimeric... 

Glutathione conjugation Glutathione GSH-S-transferase (cytosol, microsomes)... 

Table IV. GSH-S Transferase Activities In Cytosol Prcm Several Species...

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