⁶⁰Co γ radiolysis of reduced glutathione in aerated solutions at pH values between 1–7.0

Abstract

G-values for the formation of oxidised glutathione (GuS—SGu), glutathione sulphinic acid (GuSO2H), γ-glutamylalanylglycine (GuH), γ-glutamylserylglycine (GuOH), and hydrogen peroxide and G(—GuSH) have been estimated in the γ-radiolysis of aerated reduced glutathione solutions at pH values between 1–7.3. The results show excellent material balance for the radiolytic amino products. Oxygen is necessary for the production of both glutathione sulphinic acid and γ-glutamylserylglycine in the radiolysis of glutathione. Product yields increase with increasing GuSH concentration and reflect the occurrence of a small chain reaction. Although the spectrum of amino products is identical to the corresponding products from cysteine radiolysis under similar conditions, their yields are very much different. It is significant, that there is no evidence for the scission of the peptide chain, at any of the GuSH concentrations and pH's; thus the —SH group of glutathione is the site of attack of the primary species.A reaction mechanism, which explains most of the experimental results has been put forward. A rate expression for G(—GuSH) has been evaluated and it is found that the experimental and calculated G(—GuSH) are in good agreement.

Radiolysis of Glutathione in Oxygen-containing Solutions of pH 7

“…The question might be clarified by studying the radiolysis of GSH and of its derivative disulphide GSSG in chemicallydefined systems . This note supplements our preliminary reports on the radiochemical yield G(-GSH) in O2 containing solutions of pH 7, and on some pulse-radiolysis experiments (Quintiliani, Esfandi, Matsui andGorin 1973, Quintiliani, Badiello, Tamba andGorin 1976), and it complements the reports of other investigators (Lal, Armstrong andWieser 1969, Owen andWilbraham 1972), especially the recent paper by Lal (1976) which gives an analysis of the radiolysis products . Also pertinent are the numerous investigations of the radiolysis of cysteine, which have recently been reviewed, together with new experimental results, by Al-Thannon, Barton, Packer, Sims, Trumbore and Winchester (1974) .…”

“…Lal (1976) has reported that the conversion is 85 ± 10 per cent and that the other products are the derived sulphinic acid GS( :O)OH and y-glutamylserylglycine . Although the material balance is not exact, within the accuracy of the measurements the -SH titre can be set equal to [GSH] .…”

Generation of Reactive Species and Fate of Thiols during Peroxidase-Catalyzed Metabolic Activation of Aromatic Amines and Phenols

“…During the HRP-catalyzed oxidation of either p-phenetidine or acetaminophen we observed increased GSSG formation relative to controls without the phenol or the amine and a GSH-dependent oxygen uptake (13,19,20) ( Table 1). The interaction of the glutathionyl radical with oxygen generates the peroxysulfenyl radical (GSOO) which may then undergo a number of reactions (17,18). One possible fate of this radical is the generation of glutathione sulfonic acid (GSO3H) (21), but we were unable to detect this in our incubations.…”

“…There is however another radical species generated in these reactions-the thiyl radical, and whether or not the removal of amine or phenoxy radicals by GSH is M-00-00-00QA ow-I 01%-rp, 'I 010 I".11.0.1-'k indeed a true detoxification reaction depends on the subsequent fate of the glutathionyl radical. Thiyl radicals are known to dimerize to form oxidized gluathione (GSSG) and to interact with oxygen (17,18). During the HRP-catalyzed oxidation of either p-phenetidine or acetaminophen we observed increased GSSG formation relative to controls without the phenol or the amine and a GSH-dependent oxygen uptake (13,19,20) ( Table 1).…”

“…4) as well as regenerating the glutathionyl radical (GS') would produce glutathione sulfenyl hydroperoxide (GSOOH). The fate of this species is unknown, but on the basis of extensive work on the radiolysis of thiols in aqueous solution (17,18,22,23) rearrangement to glutathione sulfinic acid (GSO2H) or hydrolysis eventually leading to the generation of GSSG are two possible pathways (Fig. 4).…”