S-NITROSOGLUTATHIONE AS A SUBSTRATE FOR GAMMA-GLUTAMYL-TRANSPEPTIDASE

S-Nitrosoglutathione (GSNO) has been used as a nitric oxide ((.) NO) d onor compound and has also been postulated to be involved in the trans port 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 t o give glutamate and cysteinylglycine. gamma-GT accelerated the decomp osition of GSNO, forming S-nitrosocysteinylglycine (CG-SNO) by a mecha nism inhibitable by the gamma-GT inhibitors acivicin and S-methylgluta thione. The K-m of gamma-GT for GSNO was found to be 28 mu M. In the p resence of contaminating transition metal ions, gamma-GT accelerated t he release of (.) NO from GSNO, as CG-SNO is more susceptible to trans ition metal ion-dependent decomposition than GSNO. However, in the pre sence of the transition metal ion chelator diethylenetriaminepentaacet ic acid, neither GSNO nor CG-SNO decomposed to generate (.) NO. Neithe r S-methylglutathione nor acivicin affected the vasodilatory response to GSNO in an isolated perfused rat heart. However, rat kidney homogen ate stimulated the decomposition of GSNO by an acivicin-inhibitable me chanism. It is likely therefore that gamma-GT is involved in the decom position of GSNO in the kidney but not in the heart.