S-Nitrosoglutathione as a substrate for γ-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 γ-glutamyl transpeptidase (γ-GT), an enzyme that hydrolyses the γ-glutamyl moiety of glutathione to give glutamate and cysteinylglycine. γ-GT accelerated the decomposition of GSNO, forming S-nitrosocysteinylglycine (CG-SNO) by a mechanism inhibitable by the γ-GT inhibitors acivicin and S-methylglutathione. The K(m) of γ-GT for GSNO was found to be 28 μM. In the presence of contaminating transition metal ions, γ-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 γ-GT is involved in the decomposition of GSNO in the kidney but not in the heart.