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. 1997 Apr 15;323(Pt 2):477–481. doi: 10.1042/bj3230477

S-Nitrosoglutathione as a substrate for gamma-glutamyl transpeptidase.

N Hogg 1, R J Singh 1, E Konorev 1, J Joseph 1, B Kalyanaraman 1
PMCID: PMC1218344  PMID: 9163341

Abstract

S-Nitrosoglutathione (GSNO) has been used as a nitric oxide (.NO) donor compound and has also been postulated to be involved in the transport of .NO in vivo. In this study we have examined the possibility that GSNO is a substrate for gamma-glutamyl transpeptidase (gamma-GT), an enzyme that hydrolyses the gamma-glutamyl moiety of glutathione to give glutamate and cysteinylglycine. gamma-GT accelerated the decomposition of GSNO, forming S-nitrosocysteinylglycine (CG-SNO) by a mechanism inhibitable by the gamma-GT inhibitors acivicin and S-methylglutathione. The Km of gamma-GT for GSNO was found to be 28 microM. In the presence of contaminating transition metal ions, gamma-GT accelerated the release of ;NO from GSNO, as CG-SNO is more susceptible to transition metal ion-dependent decomposition than GSNO. However, in the presence of the transition metal ion chelator diethylenetriaminepentaacetic acid, neither GSNO nor CG-SNO decomposed to generate .NO. Neither S-methylglutathione nor acivicin affected the vasodilatory response to GSNO in an isolated perfused rat heart. However, rat kidney homogenate stimulated the decomposition of GSNO by an acivicin-inhibitable mechanism. It is likely therefore that gamma-GT is involved in the decomposition of GSNO in the kidney but not in the heart.

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Selected References

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  1. Butler A. R., Flitney F. W., Williams D. L. NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in biology: a chemist's perspective. Trends Pharmacol Sci. 1995 Jan;16(1):18–22. doi: 10.1016/s0165-6147(00)88968-3. [DOI] [PubMed] [Google Scholar]
  2. Capraro M. A., Hughey R. P. Use of acivicin in the determination of rate constants for turnover of rat renal gamma-glutamyltranspeptidase. J Biol Chem. 1985 Mar 25;260(6):3408–3412. [PubMed] [Google Scholar]
  3. De Groote M. A., Granger D., Xu Y., Campbell G., Prince R., Fang F. C. Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6399–6403. doi: 10.1073/pnas.92.14.6399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gaston B., Reilly J., Drazen J. M., Fackler J., Ramdev P., Arnelle D., Mullins M. E., Sugarbaker D. J., Chee C., Singel D. J. Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10957–10961. doi: 10.1073/pnas.90.23.10957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Girard P., Potier P. NO, thiols and disulfides. FEBS Lett. 1993 Mar 29;320(1):7–8. doi: 10.1016/0014-5793(93)81645-g. [DOI] [PubMed] [Google Scholar]
  6. Gordge M. P., Hothersall J. S., Neild G. H., Dutra A. A. Role of a copper (I)-dependent enzyme in the anti-platelet action of S-nitrosoglutathione. Br J Pharmacol. 1996 Oct;119(3):533–538. doi: 10.1111/j.1476-5381.1996.tb15704.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gordge M. P., Meyer D. J., Hothersall J., Neild G. H., Payne N. N., Noronha-Dutra A. Copper chelation-induced reduction of the biological activity of S-nitrosothiols. Br J Pharmacol. 1995 Mar;114(5):1083–1089. doi: 10.1111/j.1476-5381.1995.tb13317.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hogg N., Singh R. J., Kalyanaraman B. The role of glutathione in the transport and catabolism of nitric oxide. FEBS Lett. 1996 Mar 18;382(3):223–228. doi: 10.1016/0014-5793(96)00086-5. [DOI] [PubMed] [Google Scholar]
  9. Joseph J., Kalyanaraman B., Hyde J. S. Trapping of nitric oxide by nitronyl nitroxides: an electron spin resonance investigation. Biochem Biophys Res Commun. 1993 Apr 30;192(2):926–934. doi: 10.1006/bbrc.1993.1504. [DOI] [PubMed] [Google Scholar]
  10. Konorev E. A., Tarpey M. M., Joseph J., Baker J. E., Kalyanaraman B. S-nitrosoglutathione improves functional recovery in the isolated rat heart after cardioplegic ischemic arrest-evidence for a cardioprotective effect of nitric oxide. J Pharmacol Exp Ther. 1995 Jul;274(1):200–206. [PubMed] [Google Scholar]
  11. Mathews W. R., Kerr S. W. Biological activity of S-nitrosothiols: the role of nitric oxide. J Pharmacol Exp Ther. 1993 Dec;267(3):1529–1537. [PubMed] [Google Scholar]
  12. McIntyre T. M., Curthoys N. P. Comparison of the hydrolytic and transfer activities of rat renal gamma-glutamyltranspeptidase. J Biol Chem. 1979 Jul 25;254(14):6499–6504. [PubMed] [Google Scholar]
  13. Meister A., Tate S. S., Griffith O. W. Gamma-glutamyl transpeptidase. Methods Enzymol. 1981;77:237–253. doi: 10.1016/s0076-6879(81)77032-0. [DOI] [PubMed] [Google Scholar]
  14. Orning L., Hammarström S., Samuelsson B. Leukotriene D: a slow reacting substance from rat basophilic leukemia cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2014–2017. doi: 10.1073/pnas.77.4.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Park J. W., Billman G. E., Means G. E. Transnitrosation as a predominant mechanism in the hypotensive effect of S-nitrosoglutathione. Biochem Mol Biol Int. 1993 Aug;30(5):885–891. [PubMed] [Google Scholar]
  16. Poderoso J. J., Carreras M. C., Lisdero C., Riobó N., Schöpfer F., Boveris A. Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys. 1996 Apr 1;328(1):85–92. doi: 10.1006/abbi.1996.0146. [DOI] [PubMed] [Google Scholar]
  17. Radomski M. W., Rees D. D., Dutra A., Moncada S. S-nitroso-glutathione inhibits platelet activation in vitro and in vivo. Br J Pharmacol. 1992 Nov;107(3):745–749. doi: 10.1111/j.1476-5381.1992.tb14517.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Singh R. J., Hogg N., Joseph J., Kalyanaraman B. Mechanism of nitric oxide release from S-nitrosothiols. J Biol Chem. 1996 Aug 2;271(31):18596–18603. doi: 10.1074/jbc.271.31.18596. [DOI] [PubMed] [Google Scholar]
  19. Singh R. J., Hogg N., Neese F., Joseph J., Kalyanaraman B. Trapping of nitric oxide formed during photolysis of sodium nitroprusside in aqueous and lipid phases: an electron spin resonance study. Photochem Photobiol. 1995 Apr;61(4):325–330. doi: 10.1111/j.1751-1097.1995.tb08616.x. [DOI] [PubMed] [Google Scholar]
  20. Wink D. A., Nims R. W., Darbyshire J. F., Christodoulou D., Hanbauer I., Cox G. W., Laval F., Laval J., Cook J. A., Krishna M. C. Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. Insights into the fate and physiological effects of intermediates generated in the NO/O2 reaction. Chem Res Toxicol. 1994 Jul-Aug;7(4):519–525. doi: 10.1021/tx00040a007. [DOI] [PubMed] [Google Scholar]
  21. de Belder A. J., MacAllister R., Radomski M. W., Moncada S., Vallance P. J. Effects of S-nitroso-glutathione in the human forearm circulation: evidence for selective inhibition of platelet activation. Cardiovasc Res. 1994 May;28(5):691–694. doi: 10.1093/cvr/28.5.691. [DOI] [PubMed] [Google Scholar]

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