Human glutathione transferase catalysis of the formation of S-nitrosoglutathione from organic nitrites plus glutathione

Abstract

The kinetics of spontaneous and human glutathione transferase catalysed formation of S-nitrosoglutathione(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 × k 2) × 10 −4, due to purified human GSH transferases A1−1, A2−2 and Mla−la 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.