Significance of the intramolecular transformation of glutathione thiyl radicals to α-aminoalkyl radicals. Thermochemical and biological implications

Abstract

Product studies have been undertaken on the OH˙ radical-induced oxidation of glutathione in N₂O- saturated aqueous solutions. Ammonia has been found to be a prominent product with G values around 2.5–2.9 × 10^-7 J mol^-1 from pH 6 to 10.5. The ammonia is considered to be a product of the disproportionation reaction of the α-amino carbon-centred radicals, formed via the intramolecular transformation of glutathione thiyl radicals. At pH ca. 4–6, the ammonia yield decreases due to the fact that the transformation reaction slows down with decreasing pH and eventually comes into competition with bimolecular recombination. From the pH dependence of the ammonia yield curve, the equilibrium constant between the glutathione thiyl radical and the α-amino carbon-centred radical is deduced to be >10⁴. The strength of the C–H bond α to the NH₂ and CO₂^- groups is thus <343 kJ mol^-1. The corresponding bond energy of the C–H bond α to the NH₂ and CO₂H groups is estimated to be <329 kJ mol^-1. Based on the ammonia formation, consumption of free SH groups and the HPLC chromatograms obtained at different pH values after γ-irradiation of N₂O-saturated glutathione solutions, the overall reaction mechanism concerning the fate of glutathione thiyl radicals is proposed. This mechanism and its kinetics indicate that the intramolecular transformation is one of the principal pathways of self-removal of glutathione thiyl radicals, which is formed in various repair processes, in both anaerobic and aerobic conditions.