REACTIVE INORGANIC OXY-SPECIES OF C, N, S, AND P - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 250

the reactivity of the HPO •− radical was higher than that of the PO 4 • − radical
[377, 378]. The reaction mechanisms for the oxidation of Trp and Tyr peptides
by phosphate radicals were studied by observing the spectra of transients. The
organic radicals were formed from reaction (5.73):

HPO

•− +

Gly-Trp or Tyr-Gly ( ) → organic radicals . (5.73)

4

The phenoxy radical of Tyr as one of the organic radicals was detected as
an intermediate involved in the oxidation of Tyr by HPO •− [378].

5.5 CONCLUSIONS

Carbonate, nitrogen dioxide, sulfate, and phosphate radicals are one-electron
oxidants, while peroxynitrite is considered a two-electron oxidant. Peroxyni-
trite can be derived through • OH, • NO 2 , and CO •− in the absence and presence
of CO 2 . Rate constants for the reactions of one- and two-electron oxidants of
biological importance with sulfur-containing molecules are compared in Table
5.11 [127, 267, 268, 394-400]. Hydrogen sulfide is an endogenously generated
gaseous molecule and can mediate a wide range of biological responses and
is therefore included as a substrate in comparing reactivities [397, 401]. Per-
oxynitrite reacted much faster than hydrogen peroxide (Table 5.11). This may
be related to the leaving-group tendency of these oxidants (HNOOH;
p K a = 3.15 vs. p K a = 15.7). The calculation for the intrinsic reactivity of HS −
from the data in Table 5.11 showed that the reactivity of HS − with oxidants
was faster than Cys and gSH. Hydrogen sulfide is a less favorable target by
oxidants in vivo unless its local concentration is high. One-electron oxidation
of thiols yielded thiyl radicals (RS • ), which could (1) recombine to form disul-
fides, (2) react with oxygen to yield secondary radicals (e.g., RSOO • ), and (3)
react with a thiolate to yield a reductive disulfide radical anion (RSSR •− ). The
radical anion can react with oxygen to form superoxide, which may also react
with thiols to initiate the oxygen-dependent chain reaction.
Peroxynitrite is very reactive against the Cys, Met, Trp, Tyr, Phe, and His
residues in proteins. The significance of peroxynitrite in the biological environ-
ment is also related to the rates of its formation and decay and to the diffusion
across membranes of the involved species [133]. The levels of CO 2 present in
biological systems also need to be considered to assess the role of peroxyni-
trite. While performing studies on reactions of peroxynitrite with heme pro-
teins, simple spectroscopic methods such as UV-visible spectroscopy have
been used. Future studies may examine intermediates of the reactions by using
additional analytical methods such as Mössbauer, EPR, and x-ray absorption
spectroscopies [402, 403]. Further studies are needed to understand the impor-
tance of nitrated protein modifications in normal cellular function and in