The Catalytic Role of Carbon Dioxide in the Decomposition of Peroxynitrite

Abstract

The fast reaction of peroxynitrite with CO 2 and the high concentration of dissolved CO 2 in vivo (ca. 1 mM) suggest that CO 2 modulates most of the reactions of peroxynitrite in biological systems. The addition of peroxynitrite to CO 2 produces the adduct ONOO-CO 2 − ( 1). The production of 1 greatly accelerates the decomposition of peroxynitrite to give nitrate. We now show that the formation of 1 is followed by reformation of CO 2 (rather than another carbonate species such as CO 3 = or HCO 3 −). To show this, it is necessary to study systems with limiting concentrations of CO 2. (When CO 2 is present in excess, its concentration remains nearly constant during the decomposition of peroxynitrite, and the recycling of CO 2, although it occurs, can not be detected kinetically). We find that CO 2 is a true catalyst of the decomposition of peroxynitrite, and this fundamental insight into its action must be rationalized by any in vivo or in vitro reaction mechanism that is proposed. When the concentration of CO 2 is lower than that of peroxynitrite, the reformation of CO 2 amplifies the fraction of peroxynitrite that reacts with CO 2. Even low concentrations of CO 2 that result from the dissolution of ambient CO 2 can have pronounced catalytic effects. These effects can cause deviations from predicted kinetic behavior in studies of peroxynitrite in noncarbonate buffers in vitro, and since 1 and other intermediates derived from it are oxidants and/or nitrating agents, some of the reactions attributed to peroxynitrite may depend on the availability of CO 2.