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 N 2 Osaturated aqueous solutions. Ammonia has been found to be a prominent product with G values around 2.5-2.9 × 10 Ϫ7 J mol Ϫ1 from pH 6 to 10.5. The ammonia is considered to be a product of the disproportionation reaction of the -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 -amino carbon-centred radical is deduced to be >10 4 . The strength of the C-H bond to the NH 2 and CO 2 Ϫ groups is thus <343 kJ mol Ϫ1 . The corresponding bond energy of the C-H bond to the NH 2 and CO 2 H groups is estimated to be <329 kJ mol Ϫ1 . Based on the ammonia formation, consumption of free SH groups and the HPLC chromatograms obtained at different pH values after -irradiation of N 2 O-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.

Hydrogen Exchange Equilibria in Glutathione Radicals: Rate Constants

“…We reinterpret the published pulse radiolysis data of glutathione and show that the formation of C-centered radicals takes place extremely rapidly, but also that more than one C-centered radical species participates in reaction 3 . While the fast formation of α C-radicals from S-radicals is reported in the literature ( 23 ), we propose the additional formation of β C (or γ C-)-radicals. These reactions have been investigated under both alkaline and acidic conditions and will, therefore, also take place at neutral pH.…”

“…The formation and reactivity of both GS • and GSSG •− radical types have been studied for nearly a half a century (20−23). In the 1980s, it was reported that not only S-centered radicals but also C-centered radicals are part of the chemistry of the GS • radical (24).…”

Mechanism of O2activation and substrate hydroxylation in noncoupled binuclear copper monooxygenases

“…Thus, a correction of -7.8 kcal/mol was applied to the HAA ΔG ‡ in PHM to give a corrected barrier height of ΔG ‡ = +14.4 kcal/mol, which is consistent with the ∼14 kcal/mol obtained experimentally from the temperature dependence of the intrinsic isotope effect. Similarly, the calculated thermodynamics of HAA from FmG were calibrated to experimental bond dissociation enthalpies (21,22), giving a corrected value of ΔG HAA = +6.7 kcal/mol in PHM (see SI Appendix for details).…”

Intramolecular Hydrogen Transfer Reactions of Thiyl Radicals from Glutathione: Formation of Carbon-Centered Radical at Glu, Cys, and Gly

“…24,39 The low BDE of α C-H (Gln) is consistent with the experimental observation of the formation of an α C-centered radical at the Gln moiety. 18 On the other hand, the calculated free energy of activation for the H-atom transfer reaction between GS • and the α C-H bond at Gly is hindered by a barrier of 134 kJ mol −1 . 24 …”