RAPID OXIDATION OF DL-SELENOMETHIONINE BY PEROXYNITRITE

Peroxynitrite, the reaction product of nitric oxide and superoxide, ra pidly oxidizes DL-selenomethionine (MetSe) with overall second-order k inetics, first-order in peroxynitrite and first-order in MetSe. The ox idation of MetSe by peroxynitrite goes by two competing mechanisms. Th e first produces ethylene by what we propose to be a one-electron oxid ation of MetSe. In the second mechanism, MetSe undergoes a two-electro n oxidation that gives methionine selenoxide (MetSe=O); the apparent s econd-order rate constant, k(2(app)), for this process is (2.4 +/- 0.1 ) x 10(3) M(-1)s(-1) at pH 7.4 and 25 degrees C. The kinetic modeling of the experimental data suggests that both peroxynitrous acid (k(2) = 20,460 +/- 440 M(-1)s(-1) at 25 degrees C) and the peroxynitrite anio n (k(3) = 200 +/- 170 M(-1)s(-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 (M et) 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 hav e different kinetic orders. These results are analogous to those we pr eviously reported for methionine and 2-keto-4-thiomethylbutanoic acid (KTBA), where ethylene is produced in a first-order reaction and sulfo xide in a second-order reaction. Therefore, we suggest that the reacti on of peroxynitrite 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 a nd reacts with second-order kinetics.