Wa. Pryor et al., ONE-ELECTRON AND 2-ELECTRON OXIDATIONS OF METHIONINE BY PEROXYNITRITE, Proceedings of the National Academy of Sciences of the United Statesof America, 91(23), 1994, pp. 11173-11177
Peroxynitrite is stable, but its acid, HOONO, either rearranges to for
m nitrate or oxidizes nearby biomolecules. We report here the reaction
s of HOONO with methionine and the methionine analog 2-keto-4-thiometh
ylbutanoic acid (KTBA). These oxidations proceed by two competing mech
anisms. The first yields the sulfoxide; the second-order rate constant
s, k(2), for this process for methionine and KTBA are 181 +/- 8 and 27
7 +/- 11 M(-1).s(-1), respectively, at pH 7.4 and 25 degrees C. In the
second mechanism, methionine or KTBA undergoes a one-electron oxidati
on that ultimately gives ethylene. We propose that the one-electron ox
idant is an activated form of peroxynitrous acid, HOONO, that is form
ed in a steady state mechanism. The ratios of the second-order rate co
nstants for the ethylene-producing reaction (k(2)()) and the first-or
der rate constant to produce nitric acid (k(N)) for methionine and KTB
A, k(2)()/k(N), are 1250 +/- 290 and 6230 +/- 1390 M(-1), respectivel
y. Both eerie and peroxydisulfate ions also oxidize KTBA to ethylene,
confirming a one-electron transfer mechanism. The yields of neither Me
tSO nor ethylene are affected by several hydroxyl radical scavengers,
suggesting that a unimolecular homolysis of HOONO to HO. and (NO2)-N-.
is not involved in these reactions. HOONO gives hydroxyl radical-lik
e products from various substrates but displays more selectivity than
does the hydroxyl radical; thus, HOONO is incompletely trapped by typ
ical HO. scavengers. However, a mechanism involving dissociation of HO
ONO to caged radicals cannot be ruled out at this time.