HUMAN GLUTATHIONE TRANSFERASE CATALYSIS OF THE FORMATION OF S-NITROSOGLUTATHIONE FROM ORGANIC NITRITES PLUS GLUTATHIONE

The kinetics of spontaneous and human glutathione transferase catalysed formation of S-nitrosogtutathione(GSNO) from glutathione(GSH) and n-butyl- or amyl nitrite have been studied. At physiological pH and temperature, k(2) values of 22.3 and 21.0 M(-1) min(-1) were obtained for n-butyl- and amyl nitrites, respectively. Rate enhancements, (k(cat)/K-m x k(2)) x 10(-4), due to purified human GSH transferases A1-1,A2-2 and M1a-1a were, respectively, 7.00, 2.94 and 10.6 for n-butyl nitrite and 121, 3.92 and 34.5 for amyl nitrite. GSH transferase P1-1 showed no detectable catalysis of the formation of GSNO. The data suggest that the presence of GSTs A1-1, A2-2 or M1-1 contribute substantially to intracellular metabolism of alkyl nitrites to GSNO. The results may be significant with regard to the immunotoxicity of alkyl nitrites.