Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 May;78(5):2777–2781. doi: 10.1073/pnas.78.5.2777

Formation of gamma-glutamycyst(e)ine in vivo is catalyzed by gamma-glutamyl transpeptidase.

O W Griffith, R J Bridges, A Meister
PMCID: PMC319440  PMID: 6114489

Abstract

These studies indicate that gamma-glutamylcyst(e)ine, found in the urine of a patient with gamma-glutamyl transpeptidase deficiency and also in the urine of experimental animals injected with glutathione or with inhibitors of gamma-glutamyl transpeptidase, is formed by the action of gamma-glutamyltranspeptidase. The evidence demonstrates that transpeptidation between glutathione and cystine occurs in vivo and also that this reaction constitutes a significant physiological function of the enzyme. The appearance of large amounts of gamma-glutamylcyst(e)ine in the urine seems to reflect an inhibitory effect of glutathione on the transport of gamma-glutamylcyst(e)ine into cells. The findings also indicate that conversion of glutathione to gamma-glutamylcysteine by hydrolytic cleavage of the COOH-terminal glycine moiety of glutathione (or analogous cleavage of glutathione disulfide) is not a quantitatively significant pathway. The results reported here show that gamma-glutamyl transpeptidase activity is not completely absent in a patient found to have a deficiency of this enzyme and that the activity of the enzyme is not abolished in experimental animals treated with potent gamma-glutamyl transpeptidase inhibitors.

Full text

PDF
2781

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison R. D., Meister A. Evidence that transpeptidation is a significant function of gamma-glutamyl transpeptidase. J Biol Chem. 1981 Mar 25;256(6):2988–2992. [PubMed] [Google Scholar]
  2. Anderson M. E., Bridges R. J., Meister A. Direct evidence for inter-organ transport of glutathione and that the non-filtration renal mechanism for glutathione utilization involves gamma-glutamyl transpeptidase. Biochem Biophys Res Commun. 1980 Sep 30;96(2):848–853. doi: 10.1016/0006-291x(80)91433-3. [DOI] [PubMed] [Google Scholar]
  3. Griffith O. W., Bridges R. J., Meister A. Transport of gamma-glutamyl amino acids: role of glutathione and gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6319–6322. doi: 10.1073/pnas.76.12.6319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Griffith O. W., Meister A. Excretion of cysteine and gamma-glutamylcysteine moieties in human and experimental animal gamma-glutamyl transpeptidase deficiency. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3384–3387. doi: 10.1073/pnas.77.6.3384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Griffith O. W., Meister A. Glutathione: interorgan translocation, turnover, and metabolism. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5606–5610. doi: 10.1073/pnas.76.11.5606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Griffith O. W., Meister A. Selective inhibition of gamma-glutamyl-cycle enzymes by substrate analogs. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3330–3334. doi: 10.1073/pnas.74.8.3330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Griffith O. W., Meister A. Translocation of intracellular glutathione to membrane-bound gamma-glutamyl transpeptidase as a discrete step in the gamma-glutamyl cycle: glutathionuria after inhibition of transpeptidase. Proc Natl Acad Sci U S A. 1979 Jan;76(1):268–272. doi: 10.1073/pnas.76.1.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Griffith O. W., Novogrodsky A., Meister A. Translocation of glutathione from lymphoid cells that have markedly different gamma-glutamyl transpeptidase activities. Proc Natl Acad Sci U S A. 1979 May;76(5):2249–2252. doi: 10.1073/pnas.76.5.2249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Griffith O. W., Tate S. S. The apparent glutathione oxidase activity of gamma-glutamyl transpeptidase. Chemical mechanism. J Biol Chem. 1980 Jun 10;255(11):5011–5014. [PubMed] [Google Scholar]
  10. Meister A., Tate S. S. Glutathione and related gamma-glutamyl compounds: biosynthesis and utilization. Annu Rev Biochem. 1976;45:559–604. doi: 10.1146/annurev.bi.45.070176.003015. [DOI] [PubMed] [Google Scholar]
  11. Oppenheimer L., Wellner V. P., Griffith O. W., Meister A. Glutathione synthetase. Purification from rat kidney and mapping of the substrate binding sites. J Biol Chem. 1979 Jun 25;254(12):5184–5190. [PubMed] [Google Scholar]
  12. Orlowski M., Wilk S. Intermediates of the gamma-glutamyl cycle in mouse tissues. Influence of administration of amino acids on pyrrolidone carboxylate and gamma-glutamyl amino acids. Eur J Biochem. 1975 May 6;53(2):581–590. doi: 10.1111/j.1432-1033.1975.tb04101.x. [DOI] [PubMed] [Google Scholar]
  13. Sekura R., Meister A. gamma-Glutamylcysteine synthetase. Further purification, "half of the sites" reactivity, subunits, and specificity. J Biol Chem. 1977 Apr 25;252(8):2599–2605. [PubMed] [Google Scholar]
  14. Taniguchi N., Meister A. gamma-Glutamyl cyclotransferase from rat kidney. Sulfhydryl groups and isolation of a stable form of the enzyme. J Biol Chem. 1978 Mar 25;253(6):1799–1806. [PubMed] [Google Scholar]
  15. Tate S. S., Meister A. Interaction of gamma-glutamyl transpeptidase with amino acids, dipeptides, and derivatives and analogs of glutathione. J Biol Chem. 1974 Dec 10;249(23):7593–7602. [PubMed] [Google Scholar]
  16. Thompson G. A., Meister A. Hydrolysis and transfer reactions catalyzed by gamma-glutamyl transpeptidase; evidence for separate substrate sites and for high affinity of L-cystine. Biochem Biophys Res Commun. 1976 Jul 12;71(1):32–36. doi: 10.1016/0006-291x(76)90245-x. [DOI] [PubMed] [Google Scholar]
  17. Thompson G. A., Meister A. Utilization of L-cystine by the gamma-glutamyl transpeptidase-gamma-glutamyl cyclotransferase pathway. Proc Natl Acad Sci U S A. 1975 Jun;72(6):1985–1988. doi: 10.1073/pnas.72.6.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES