Rapid oxidation of DL-selenomethionine by peroxynitrite

Peroxynitrite, the reaction product of nitric oxide and superoxide, rapidly oxidizes DL-selenomethionine (MetSe) with overall second-order kinetics, first-order in peroxynitrite and first-order in MetSe. The oxidation of MetSe by peroxynitrite goes by two competing mechanism. The first produces ethylene by what we propose to be a one-electron oxidation of MetSe. In the second mechanism, MetSe undergoes a two-electron oxidation that gives methionine selenoxide (MetSe = O); the apparent second-order rate constant, k2(app), for this process is (2.4 +/- 0.1) x 10(3) M-1s-1 at pH 7.4 and 25 degrees C. The kinetic modeling of the experimental data suggests that both peroxynitrous acid (k2 = 20,460 +/- 440 M-1s-1 at 25 degrees C) and the peroxynitrite anion (k3 = 200 +/- 170 M-1s-1 at 25 degrees C) are involved in the second-order reaction leading to selenoxide. These rate constants are 10- to 1,000-fold higher than those for the reactions of methionine (Met) with peroxynitrite. With increasing concentrations of MetSe at pH 7.4, the yield of ethylene decreases, while that of MetSe = O increases, suggesting that the reactions leading to ethylene and selenoxide have different kinetic orders. These results are analogous to those we previously reported for methionine and 2-keto-4-thiomethylbutanoic acid (KTBA),where ethylene is produced in a first-order reaction and sulfoxide in a second-order reaction. Therefore, we suggest that the reaction of peryoxynitrite with MetSe involves a mechanism similar to that we proposed for Met, in which an activated intermediate of peroxynitrous acid (HOONO) is the one-electron oxidant and reacts with first-order kinetics and ground-state peroxynitrite is the two-electron oxidant and reacts with second-order kinetics.