S-Nitrosoglutathione as a substrate for gamma-glutamyl transpeptidase.
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.
Hogg
N
N
Biophysics Research Institute, Medical College of Wisconsin, 8701 Watertown Plank Rd., P.O. Box 26509, Milwaukee, WI 53226, USA.
Singh
R J
RJ
Konorev
E
E
Joseph
J
J
Kalyanaraman
B
B
D000818:Animals; D003326:Coronary Circulation; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009603:Nitroso Compounds / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026422:S-Nitrosoglutathione; D014664:Vasodilation; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D026422:S-Nitrosoglutathione; D005723:gamma-Glutamyltransferase; D005978:Glutathione