THE CATALYTIC ROLE OF CARBON-DIOXIDE IN THE DECOMPOSITION OF PEROXYNITRITE

The fast reaction of peroxynitrite with CO2 and the high concentration of dissolved CO2 in vivo (ca. 1 mM) suggest that CO2 modulates most o f the reactions of peroxynitrite in biological systems. The addition o f peroxynitrite to CO2 produces the adduct ONOO-CO2- (1). The producti on of 1 greatly accelerates the decomposition of peroxynitrite to give nitrate. We now show that the formation of 1 is followed by reformati on of CO2 (rather than another carbonate species such as CO3= or HCO3- ). To show this, it is necessary to study systems with limiting concen trations of CO2. (When CO2 is present in excess, its concentration rem ains nearly constant during the decomposition of peroxynitrite, and th e recycling of CO2, although it occurs can not be detected kinetically ). We find that CO2 is a true catalyst of the decomposition of peroxyn itrite, and this fundamental insight into its action must be rationali zed by any in vivo or in vitro reaction mechanism that is proposed. Wh en the concentration of CO2 is lower than that of peroxynitrite, the r eformation of CO2 amplifies the fraction of peroxynitrite that reacts with CO2. Even low concentrations of CO2 that result from the dissolut ion of ambient CO2 can have pronounced catalytic effects. These effect s can cause deviations from predicted kinetic behavior in studies of p eroxynitrite in noncarbonate buffers in vitro, and since 1 and other i ntermediates derived from it are oxidants and/or nitrating agents, som e of the reactions attributed to peroxynitrite may depend on the avail ability of CO2. (C) 1997 Elsevier Science Inc.