The Glutathione Transferases in Detoxification

  • W. B. Jakoby
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Summary

The glutathione transferases (EC 2.5.1.18) appear to perform several detoxification functions. This group of enzvmes is analogous to serum albumin in the broad spectrum of compounds that serve as ligands, but differs significantly in that the transferases have an additional and specific site for GSH. They appear to catalyze all reactions that would be expected of GSH acting as a nucleophile, providing that the electro-philic substrate is bound to the enzyme. Examples of the reactions catalyzed include conjugation to compounds with a reactive electrophilic carbon to form thioethers; reactions with other electrophilic atoms including the nitrogen of organic nitrates and the sulfur of organic thiocyanates; isomerization; disulfide interchange; glutathione peroxidase activity with organic peroxides; and the formation of a thiolester from p-nitrophenylacetate.

The enzymes have been shown to act as storage proteins and appear to be responsible for the binding of bilirubin and its conjugates, among many other compounds, within the hepatocyte. A more speculative scavenger function has also been suggested for them.

These enzymes are widely distributed in higher animals and constitute 10% and 3%, respectively, of the extractable protein of rat and human liver.

Keywords

Sludge Glutathione Cortisol Cysteine Polycyclic Aromatic Hydrocarbon 

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References

  1. 1.
    Jakoby, W.B., Keen, J.H.: Trends Biochem. Sci. 2, 229–231 (1977)CrossRefGoogle Scholar
  2. 2.
    Jakoby, W.B., Ketley, J.N., Habig, W.H.: In: Glutathione: metabolism and function. Arias, I.M., Jakoby, W.B. (eds.), pp. 213–223. New York: Raven Press 1976Google Scholar
  3. 3.
    Kamisaka, K., Habig, W.H., Ketley, J.N., Arias, I.M., Jakoby, W.B.: Eur. J. Biochem. 60, 153–161 (1975)PubMedCrossRefGoogle Scholar
  4. 4.
    Boyland, E., Chasseaud, L.F.: Adv. Enzymol. 32, 172–219 (1969)Google Scholar
  5. 5.
    Jakoby, W.B.: Adv. Enzymol. 46, 383–414 (1978)PubMedGoogle Scholar
  6. 6.
    Mannervik, B., Askelof, P.: FEBS Lett. 56, 218 (1975)PubMedCrossRefGoogle Scholar
  7. 7.
    Pabst, M.J., Habig, W.H., Jakoby, W.B.: J. Biol. Chem. 249, 7140–7150 (1974)PubMedGoogle Scholar
  8. 8.
    Keen, J.H., Habig, W.H., Jakoby, W.B.: J. Biol. Chem. 251, 6283–6288 (1976)Google Scholar
  9. 9.
    Keen, J.H., Jakoby, W.B.: J. Biol. Chem. 253, 5654–5657 (1978)PubMedGoogle Scholar
  10. 10.
    Jakoby, W.B., Habig, W.H., Keen, J.H., Ketley, J.N., Pabst, M.J.: In: Glutathione: metabolism and function. Arias, I.M., Jakoby, W.B. (eds.), pp.189–211. New York: Raven Press 1976Google Scholar
  11. 11.
    Tate, S.S., Meister, A.: J. Biol. Chem. 249, 7593–7602 (1974)PubMedGoogle Scholar
  12. 12.
    Benson, A.M., Talalay, P., Keen, J.H., Jakoby, W.B.: Proc. Nat. Acad. Sci. U.S.A. 74, 158–162 (1977)CrossRefGoogle Scholar
  13. 13.
    Prohaska, J.R., Ganther, H.E.: Biochem. Biophys. Res. Commun. 76, 437–445 (1977)CrossRefGoogle Scholar
  14. 14.
    Scher, W., Jakoby, W.B.: J. Biol. Chem. 244, 1878–1882 (1969)PubMedGoogle Scholar
  15. 15.
    Jencks, W.P.: Catalysis in chemistry and enzymology, pp.4–5. New York: McGraw-Hill 1969Google Scholar
  16. 16.
    Reyes, A., Levi, A.J., Arias, I.M.: J. Clin. Invest. 50, 2242–2252 (1971)PubMedCrossRefGoogle Scholar
  17. 17.
    Morey, K.S., Litwack, G.: Biochemistry 8, 4813–4821 (1969)PubMedCrossRefGoogle Scholar
  18. 18.
    Ketterer, B., Ross-Mansell, P., Whitehead, J.K.: Biochem. J. 103, 316–324 (1967)PubMedGoogle Scholar
  19. 19.
    Litwack, G., Ketterer, B., Arias, I.M.: Nature (London) 234, 466–467 (1971)CrossRefGoogle Scholar
  20. 20.
    Habig, W.H., Pabst, M.J., Fleischner, G., Gatmaitan, Z., Arias, I.M., Jakoby, W.B.: Proc. Nat. Acad. Sci. U.S.A. 71, 3879–3882 (1974)CrossRefGoogle Scholar
  21. 21.
    Ketley, J.N., Habig, W.H., Jakoby, W.B.: J. Biol. Chem. 250, 8670–8673 (1975)PubMedGoogle Scholar
  22. 22.
    Wolkoff, A.W., Ketley, J.N., Waggoner, J.G., Berk, P.D., Jakoby, W.B.: J. Clin. Invest. 61, 142–149 (1978)PubMedCrossRefGoogle Scholar
  23. 23.
    Wolkoff, A.W., Weisiger, R.A., Jakoby, W.B.: In: Progress in liver diseases. Popper, H., Schassner, F. (eds.), Vol.6. In press (1979)Google Scholar
  24. 24.
    Miller, E.C., Miller, J.A.: In: Molecular biology of cancer. Busch, H. (ed.), pp.377–402. New York: Academic Press 1974Google Scholar
  25. 25.
    Stadtman, T.C.: Nutrition Reviews 35, 161 (1977)PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1978

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  • W. B. Jakoby

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