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.