REACTIVE INORGANIC OXY-SPECIES OF C, N, S, AND P - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 236

5.6) to yield sulfonate (Table 5.7) [216]. In addition to disulfide and sulfonate,
the disulfide radical anion (RSSR •− ), sulfinyl radical (RSO • ), and nitroso- and
nitrothiol have been detected (Table 5.7) [41, 271].
The oxidation of selenium-containing compounds, selenomethionine, sele-
nocysteine, and ebselen (2-phenyl-11,2-benzisoselenazol-3(2H)-one) by per-
oxynitrite has been performed (Table 5.6). The selenium compounds reacted
much faster than their sulfur analogues (Table 5.6). Peroxynitrite reacts with
ebselen at a rate constant of 2 × 10 6 /M/s, producing selenoxide and nitrite
[272].
Among the aromatic amino acids, Trp had a direct reaction (Table 5.6),
while His, Phe, and Tyr did not react directly with peroxynitrite. The formation
of the tryptophan radical and nitrate products were observed, with increasing
concentrations in the presence of CO 2 (Table 5.7) [41, 199, 205, 206, 207, 212,
216, 240, 248, 263, 269, 273, 274, 270, 271, 275, 276, 277, 278, 279, 280, 209].
Nitrotryptophan also formed in vitro when the protein, human Cu,Zn super-
oxide dismutase, was exposed to peroxynitrite/CO 2 [281]. A recent study
examined the modification of Trp in a number of proteins by peroxynitrite
[282]. Peroxynitrate resulted in nitration of residues of Trp to form nitrotryp-
tophan (NO 2 -Trp), which may be significant in nitrosative stress [282]. The
indirect reaction of peroxynitrite with His formed a product with a nitro addi-
tion, while Phe resulted in the formation of o-, p-, and m-tyrosine and nitro-
phenylalanine (Table 5.7). Formations of oxo- and nitro-derivatives were
observed in the reaction of peroxynitrite with histidine-containing peptides.
Nitration of tyrosine residues by peroxynitrite under physiological condi-
tions has been studied in detail [132, 283]. The mechanism of the reaction in
the presence of excess CO 2 at pH 7.5 is presented in Figure 5.15. As stated
above, peroxynitrite decomposed to ∼33% yield of CO •− and • NO 2 , and there-
fore, ∼33% of peroxynitrite formed the tyrosyl radical (TyrO • ) and • NO 2 due
to the fast reaction of CO •− with Tyr. The cross recombination of radicals
resulted in 3-nitrotyrosine. The expected yield of 3-nitrotyrosine from the
reaction of TyrO • with • NO 2 is 45%, consisting of 15% peroxynitrite. The
experimental results agreed with the expected yield [192, 284-286]. The forma-
tion of 3-nitrotyrosine in peroxynitrite-treated oxyHb, metHb, and Co-Hb
have also been reported [287]. The individual steps of the mechanism, dis-
played in Figure 5.15, were recently examined theoretically and the calculated
enthalpy changes are given in Figure 5.16 [288]. The calculations were based
on the nitration of p -methylphenol [288]. Initially, the unimolecular decompo-
sition of peroxynitrous acid or ONOOCOO − yielded CO •− and • NO 2 . The
reaction proceeded through the phenoxy radical intermediate from the reac-
tion of Tyr with CO •− . The reaction of this intermediate with • NO 2 , followed
by tautomerization, formed nitrated tyrosine. The yield of nitration depended
on the concentration of peroxynitrite and the dosage rate of peroxynitrite
[132]. dityrosine was the dimerization product of TyrO • (Fig. 5.15). Both
in vitro and in vivo studies have shown that the peroxynitrate and other nitrat-
ing species can cause nitration of Tyr to 3-nitrotyrosine in mitochondrial