INHIBITION OF PEROXYNITRITE-MEDIATED OXIDATION OF GLUTATHIONE BY CARBON-DIOXIDE

Peroxynitrite reacts with CO2 to form an adduct containing a weak O-O bond that can undergo homolytic and/or heterolytic cleavage to give ot her reactive intermediates. Because the peroxynitrite/CO2 reaction is fast and physiological concentrations of CO2 are relatively high, pero xynitrite-mediated oxidations of biological species probably involve t he peroxynitrite-CO2 adduct and its subsequent reactive intermediates, We have examined the,reaction of glutathione with peroxynitrite in th e presence and absence of added bicarbonate. In the presence of added bicarbonate, CO2 competes with glutathione for peroxynitrite, resultin g in a markedly decreased consumption of glutathione compared with tha t observed in the absence of added bicarbonate, However, the consumpti on of glutathione still is much higher than predicted from the assumpt ion that the glutathione-peroxynitrite reaction is the only reaction t hat can consume glutathione in this system. These results suggest that glutathione partially, but not completely, traps intermediate(s) deri ved from the peroxynitrite and CO2 reaction. Some rate constants for t he trapping of the intermediates are estimated by simulating the react ions, and possible mechanisms for the reaction of peroxynitrite with g lutathione in the presence of added bicarbonate are discussed. (C) 199 7 Academic Press.