Intramolecular transformation reaction of the glutathione thiyl radical into a non-sulphur-centred radical: a pulse-radiolysis and EPR study

The thiyl radical derived from glutathione (GSH) is shown to decay rapidly in aqueous solution by intramolecular rearrangement reactions into the non-sulphur-centred radical 1. The reaction is induced by OH- with a rate constant of 5 x 109 dm3 mol-1 and is also observable at near-neutral conditions (at physiological pH values around 7.5 the rate of formation of 1 amounts to ∼ 1 x 103 s-1). The activation enthalpy and entropy at pH 8.4 and 20oC were found to be 26.7 kJ mol-1 and -77 J mol-1 K-1, respectively. Radical 1 was unequivocally identified by EPR as the α-amino radical at the glutamyl residue of GSH. It is relatively long-lived with typical biomolecular decay rate constants of the order of (2-20) x 106dm3 mol-1 s-1. At higher GSH concentrations the formation of 1 is retarded but not inhibited. All radicals, sulphur- as well as non-sulphur-centred ones are connected via equilibria, partly under the action of 'repair' processes of GSH. These repair processes, however, are slow (k << 1.4 x 105 dm3 mol-1 S -1). (Author)