Influence of γ-Glutamyl Transpeptidase Inactivation on the Status of Extracellular Glutathione and Glutathione Conjugates
Glutathione-S-transferases, which catalyze the conjugation of GSH* with a large number of electrophilic chemicals, have been studied extensively as indicated by the recent review of Chasseaud, 1979. Neither the intermediary fate of these glutathione-Sconjugates nor the extent of extrahepatic sites for the initial hydrolytic reaction catalyzed by γ-glutamyl transpeptidase (EC 2.3. 2.2) is well understood. Biliary excretion of glutathione-Sconjugates from the liver can be quantitative in some instances (Wahlländer and Sies, 1979). While GSH may be released from the liver to the systemic circulation, both GSH and GSSG appear to be excreted via the bile (Sies et al., 1978). A majority of the systemic glutathione appears to be degraded extracellularly by the kidney (Hahn et al., 1978; Häberle et al., 1979). In contrast, biliary glutathione and glutathioné-S-conjugates may be substrates for γ-glutamyl transpeptidase located in canalicular plasma membranes, plasma membrane of biliary duct epithelial cells (Rutenberg et al., 1969; Tanaka, 1974) and intestinal mucosal cells (Grafström et al., 1980).
KeywordsTotal Glutathione Ethacrynic Acid Glutathione Conjugate Mercapturic Acid Diethyl Maleate
Unable to display preview. Download preview PDF.
- Allen, L., Meck, R. Yunis, A., 1980, The inhibition of y-glutamyl transpeptidase from human pancreatic carcinoma cells by (aS, 5S)-a-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125; NSC-163501), Res. Commun. Chem. Pathol. Pharmacol. 27: 175.Google Scholar
- Barnhart, J. L., Combes, B., 1978, Choleresis associated with metabolism and biliary excretion of diethyl maleate in the rat and dog, J. Pharmacol. Exptl. Therap. 206: 614.Google Scholar
- Bartoli, G. M., Häberle, D. and Sies, H., 1978, Glutathione efflux from perfused rat liver and its relation to glutathione uptake by the kidney, in Functions of Glutathione in Liver and Kidney, Sies, H. and Wendel, A., eds., Springer-Verlag, Berlin, Heidelberg, New York, pp. 27–31.Google Scholar
- Chasseaud, L. F., 1979, The role of glutathione and glutathione Stransferases in the metabolism of chemical carcinogens and other electrophilic agents, Adv. in Cancer Res. 29: 175.Google Scholar
- Fischer, G. A. and Sartorelli, A. C., 1964, Development, maintenance and assay of drug resistance, Methods in Medical Res. 10: 247.Google Scholar
- Klaassen, C. D. and Fitzgerald, T. J., 1974, Metabolism and biliary excretion of ethacrynic acid, J. Pharmacol. Exptl. Therap. 191: 548.Google Scholar
- Reed, D. J., Ellis, W. W. and Meck, R. A., 1980a, The inhibition of y-glutamyl transpeptidase and glutathione metabolism of isolated rat kidney cells by L-(aS,5S)-a-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125; NSC-163501), Biochem. Biophys. Res. Commun. 94: 1273.PubMedCrossRefGoogle Scholar
- Sies, H., Wahlländer, A., Waydhas, Ch., 1978, Properties of glutathione disulfide (GSS) and glutathione-S-conjugate released from perfused rat liver, in “Functions of Glutathione in Liver and Kidney”, Sies, H. and Wendel, A., eds., Springer-Verlag, Berlin, Heidelberg, New York, pp. 120–126.Google Scholar
- Tanaka, M., 1974, A histochemical study of the activity of y-glutamyl transpeptidase in liver disease, Acta Pathol. Jap. 24: 651.Google Scholar