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. 1970 Nov;67(3):1248–1255. doi: 10.1073/pnas.67.3.1248

The γ-Glutamyl Cycle: A Possible Transport System for Amino Acids*

Marian Orlowski 1, Alton Meister 1
PMCID: PMC283344  PMID: 5274454

Abstract

Evidence is presented that rat kidney contains enzymes that catalyze the synthesis and utilization of glutathione; these reactions, which involve the uptake and release of amino acids from γ-glutamyl linkage, constitute a cyclical process which is termed „the γ-glutamyl cycle.” The γ-glutamyl cycle has properties that fulfill the requirements of an amino acid transport system. Thus, γ-glutamyl transpeptidase may function in translocation and γ-glutamylcysteine synthetase and glutathione synthetase may catalyze energy-requiring „recovery” steps in transport. These and other considerations suggest that glutathione serves a carrier function in amino acid transport.

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Selected References

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

  1. ALBERT Z., ORLOWSKA J., ORLOWSKI M., SZEWCZUK A. HISTOCHEMICAL AND BIOCHEMICAL INVESTIGATIONS OF GAMMA-GLUTAMYL TRANSPEPTIDASE IN THE TISSUES OF MAN AND LABORATORY RODENTS. Acta Histochem. 1964 May 30;18:78–89. [PubMed] [Google Scholar]
  2. ALBERT Z., ORLOWSKI M., SZEWCZUK A. Histochemical demonstration of gamma-glutamyl transpeptidase. Nature. 1961 Aug 19;191:767–768. doi: 10.1038/191767a0. [DOI] [PubMed] [Google Scholar]
  3. Albert Z., Orlowski M., Rzucidlo Z., Orlowska J. Studies on gamma-glutamyl transpeptidase activity and its histochemical localization in the central nervous system of man and different animal species. Acta Histochem. 1966;25(5):312–320. [PubMed] [Google Scholar]
  4. BALL E. G., COOPER O., REVEL J. P. The quantitative measurement of gamma glutamyl transpeptidase activity. J Biol Chem. 1956 Aug;221(2):895–908. [PubMed] [Google Scholar]
  5. BEARN A. G., KUNKEL H. G. Abnormalities of copper metabolism in Wilson's disease and their relationship to the aminoaciduria. J Clin Invest. 1954 Mar;33(3):400–409. doi: 10.1172/JCI102912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CHRISTENSEN H. N., RIGGS T. R. Concentrative uptake of amino acids by the Ehrlich mouse ascites carcinoma cell. J Biol Chem. 1952 Jan;194(1):57–68. [PubMed] [Google Scholar]
  7. CLARKSON T. W., KENCH J. E. Urinary excretion of amino acids by men absorbing heavy metals. Biochem J. 1956 Mar;62(3):361–372. doi: 10.1042/bj0620361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CONNELL G. E., HANES C. S. Enzymic formation of pyrrolidone carboxylic acid from gamma-glutamyl peptides. Nature. 1956 Feb 25;177(4504):377–378. doi: 10.1038/177377a0. [DOI] [PubMed] [Google Scholar]
  9. Connell G. E., Szewczuk A. The properties of gamma-glutamyl lactamase in man. Clin Chim Acta. 1967 Sep;17(3):423–430. doi: 10.1016/0009-8981(67)90218-5. [DOI] [PubMed] [Google Scholar]
  10. DEMETRY J. P., AIKAWA J. K. Effect of Hg 203-labeled mercaptomerin on renal sulfhydryl concentration in normal rabbits. Proc Soc Exp Biol Med. 1955 Nov;90(2):413–415. doi: 10.3181/00379727-90-22051. [DOI] [PubMed] [Google Scholar]
  11. FODOR P. J., MILLER A., NEIDLE A., WAELSCH H. Enzymatic synthesis of glutathione by a transfer reaction. J Biol Chem. 1953 Aug;203(2):991–1002. [PubMed] [Google Scholar]
  12. FODOR P. J., MILLER A., WAELSCH H. Enzymic splitting and synthesis of glutathione. Nature. 1952 Nov 15;170(4333):841–842. doi: 10.1038/170841a0. [DOI] [PubMed] [Google Scholar]
  13. Greenberg E., Wollaeger E. E., Fleisher G. A., Engstrom G. W. Demonstration of gamma-glutamyl transpeptidase activity in human jejunal mucosa. Clin Chim Acta. 1967 Apr;16(1):79–89. doi: 10.1016/0009-8981(67)90272-0. [DOI] [PubMed] [Google Scholar]
  14. HANES C. S., HIRD F. J. R. Synthesis of peptides in enzymic reactions involving glutathione. Nature. 1950 Aug 19;166(4216):288–292. doi: 10.1038/166288a0. [DOI] [PubMed] [Google Scholar]
  15. HIRD F. J., SPRINGELL P. H. The enzymic hydrolysis of the gamma-glutamyl bond in glutathione. Biochim Biophys Acta. 1954 Sep;15(1):31–37. doi: 10.1016/0006-3002(54)90090-6. [DOI] [PubMed] [Google Scholar]
  16. Hillman R. E., Albrecht I., Rosenberg L. E. Identification and analysis of multiple glycine transport systems in isolated mammalian renal tubules. J Biol Chem. 1968 Nov 10;243(21):5566–5571. [PubMed] [Google Scholar]
  17. Hillman R. E., Rosenberg L. E. Amino acid transport by isolated mammalian renal tubules. II. Transport systems for L-proline. J Biol Chem. 1969 Aug 25;244(16):4494–4498. [PubMed] [Google Scholar]
  18. JERVIS E. L., SMYTH D. H. The active transfer of D-methionine by the rat intestine in vitro. J Physiol. 1960 Apr;151:51–58. [PMC free article] [PubMed] [Google Scholar]
  19. KAMIN H., HANDLER P. Effect of infusion of single amino acids upon excretion of other amino acids. Am J Physiol. 1951 Mar;164(3):654–661. doi: 10.1152/ajplegacy.1951.164.3.654. [DOI] [PubMed] [Google Scholar]
  20. KINOSHITA J. H., BALL E. G. A transpeptidation reaction between glutathione and arginine. J Biol Chem. 1953 Feb;200(2):609–617. [PubMed] [Google Scholar]
  21. MANDELES S., BLOCK K. Enzymatic synthesis of gamma-glutamylcysteine. J Biol Chem. 1955 Jun;214(2):639–646. [PubMed] [Google Scholar]
  22. Mooz E. D., Meister A. Tripeptide (glutathione) synthetase. Purification, properties, and mechanism of action. Biochemistry. 1967 Jun;6(6):1722–1734. doi: 10.1021/bi00858a022. [DOI] [PubMed] [Google Scholar]
  23. ORLOWSKI M., MEISTER A. GAMMA-GLUTAMYL-P-NITROANILIDE: A NEW CONVENIENT SUBSTRATE FOR DETERMINATION AND STUDY OF L- AND D-GAMMA-GLUTAMYLTRANSPEPTIDASE ACTIVITIES. Biochim Biophys Acta. 1963 Aug 6;73:679–681. doi: 10.1016/0006-3002(63)90348-2. [DOI] [PubMed] [Google Scholar]
  24. Orlowski M., Richman P. G., Meister A. Isolation and properties of gamma-L-glutamylcyclotransferase from human brain. Biochemistry. 1969 Mar;8(3):1048–1055. doi: 10.1021/bi00831a036. [DOI] [PubMed] [Google Scholar]
  25. Pardee A. B. Membrane transport proteins. Proteins that appear to be parts of membrane transport systems are being isolated and characterized. Science. 1968 Nov 8;162(3854):632–637. doi: 10.1126/science.162.3854.632. [DOI] [PubMed] [Google Scholar]
  26. ROSENBERG L. E., BLAIR A., SEGAL S. Transport of amino acids by slices of rat-kidney cortex. Biochim Biophys Acta. 1961 Dec 23;54:479–488. doi: 10.1016/0006-3002(61)90088-9. [DOI] [PubMed] [Google Scholar]
  27. ROSENBERG L. E., DOWNING S. J., SEGAL S. Competitive inhibition of dibasic amino acid transport in rat kidney. J Biol Chem. 1962 Jul;237:2265–2270. [PubMed] [Google Scholar]
  28. RUSZKOWSKI M., ARASIMOWICZ C., KNAPOWSKI J., STEFFEN J., WEISS K. Renal reabsorption of amino acids. Am J Physiol. 1962 Nov;203:891–896. doi: 10.1152/ajplegacy.1962.203.5.891. [DOI] [PubMed] [Google Scholar]
  29. Rutenburg A. M., Kim H., Fischbein J. W., Hanker J. S., Wasserkrug H. L., Seligman A. M. Histochemical and ultrastructural demonstration of gamma-glutamyl transpeptidase activity. J Histochem Cytochem. 1969 Aug;17(8):517–526. doi: 10.1177/17.8.517. [DOI] [PubMed] [Google Scholar]
  30. SNOKE J. E., BLOCH K. Studies on the mechanism of action of glutathione synthetase. J Biol Chem. 1955 Apr;213(2):825–835. [PubMed] [Google Scholar]
  31. SNOKE J. E., YANARI S., BLOCH K. Synthesis of glutathione from gamma-glutamylcysteine. J Biol Chem. 1953 Apr;201(2):573–586. [PubMed] [Google Scholar]
  32. SZEWCZUK A., BARANOWSKI T. PURIFICATION AND PROPERTIES OF GAMMA-GLUTAMYL TRANSPEPTIDASE FROM BEEF KIDNEY. Biochem Z. 1963;338:317–329. [PubMed] [Google Scholar]
  33. Stern J. R., Eggleston L. V., Hems R., Krebs H. A. Accumulation of glutamic acid in isolated brain tissue. Biochem J. 1949;44(4):410–418. [PMC free article] [PubMed] [Google Scholar]
  34. TENENHOUSE A., QUASTEL J. H. Amino acid accumulation in Ehrlich ascites carcinoma cells. Can J Biochem Physiol. 1960 Nov;38:1311–1326. [PubMed] [Google Scholar]
  35. WEBBER W. A., BROWN J. L., PITTS R. F. Interactions of amino acids in renal tubular transport. Am J Physiol. 1961 Feb;200:380–386. doi: 10.1152/ajplegacy.1961.200.2.380. [DOI] [PubMed] [Google Scholar]
  36. WEBBER W. A. Interactions of neutral and acidic amino acids in renal tubular transport. Am J Physiol. 1962 Mar;202:577–583. doi: 10.1152/ajplegacy.1962.202.3.577. [DOI] [PubMed] [Google Scholar]
  37. Wilson O. H., Scriver C. R. Specificity of transport of neutral and basic amino acids in rat kidney. Am J Physiol. 1967 Jul;213(1):185–190. doi: 10.1152/ajplegacy.1967.213.1.185. [DOI] [PubMed] [Google Scholar]

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