Decomposition of S-nitrosoglutathione in the presence of copper ions and glutathione.
The decomposition of S-nitrosoglutathione (GSNO) in the presence of Cu2+ and glutathione (GSH) was studied by stopped-flow/rapid-scan spectroscopy. Reduction of Cu2+ by GSH and subsequent formation of a GS-*Cu+ complex occurred within 200 ms, with the amount of complex formed depending on the GSH-to-Cu2+ ratio. The rate of GSNO decomposition at a fixed concentration of Cu2+ increased linearly with the concentration of GSH at low GSH-to-Cu2+ ratios (< or = 0.2), but sharply declined at higher ratios. The same pattern was observed for the rate of NO. release, measured with an NO.-sensitive electrode. GSNO decomposition and NO. release in the presence of GSH and/or Cu2+ were completely inhibited by the Cu+ chelator neocuproine, but unaffected by the Cu2+ chelator cuprizone. Ascorbate and cysteine, which will reduce Cu2+ but have little or no affinity for Cu+, also stimulated GSNO decomposition in the presence of Cu2+, but did not inhibit it at higher concentrations. It is concluded that the homolytic cleavage of GSNO is efficiently catalyzed by Cu+ and that the GS-*Cu+ complex is catalytically inactive. By determining the anaerobic GSNO decomposition rates in the presence of varying concentrations of Cu+ a value of 4 x 10(3)M(-1) x s(-1) was derived for the apparent Cu+-GSNO association rate constant.
Gorren
A C
AC
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Graz, Austria.
Schrammel Astrid
Schmidt
K
K
Mayer
B
B
D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D003471:Cuprizone / Q000494:pharmacology; D005609:Free Radicals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D019803:Glutathione Disulfide; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008670:Metals / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D009603:Nitroso Compounds / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000494:pharmacology; D026422:S-Nitrosoglutathione; D013053:Spectrophotometry
D002614:Chelating Agents; D005609:Free Radicals; D008670:Metals; D009603:Nitroso Compounds; D010618:Phenanthrolines; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D003471:Cuprizone; D003300:Copper; C002701:neocuproine; D005978:Glutathione; D019803:Glutathione Disulfide