REACTIVE OXYGEN SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 126

substitution or as a moderate one-electron reducing agent with numerous
transition metal complexes and organic compounds [19, 42-45]. O •− also acts
as a weak base with acidic compounds, and hence, a proton transfer is involved
[42, 43]. Both proton transfer and radical transfer pathways occur when phe-
nolic compounds react with O •− [46, 47].
The rates of reactions of superoxide with amino acids were performed
because amino acids are building blocks of large molecules (e.g., protein). The
second-order rate constants were found to be relatively low [48]. The second-
order rate constants for the reactions of HO • were in the range of 1 × 10 1 /M/s
for aliphatic amino acids to ∼6 × 10 2 /M/s for cys. comparatively, the rate con-
stants for the reactions of O •− with amino acids were significantly smaller and
ranged from 1.0 × 10 −1 /M/s to ∼2 × 10 1 /M/s. Such difference in reactivity of two
superoxide species may be that HO • acts like a weak oxidizing agent, while
O •− behaves as both a weak oxidizing and reducing agent. Furthermore, a rate
constant represents composite of many reactions depending on the fractions
of HO /O
2

• •− and protonated/unprotonated forms of amino acids. Other sulfur-
containing amino acids, such as cystine and Met, were unreactive with super-
oxide. However, thiols such as dithiothreitol, N -acetylcysteine, and glutathione
(gSH) showed significant reactivity with rate constants of 3.5 × 10 1 /M/s,
6.8 × 10 1 /M/s, and 2.4 × 10 1 /M/s, respectively [49-51]. The relative reactivity of
thiols with superoxide inversely correlated with p K a of thiols. The ab initio
molecular calculations suggested the main pathway of formation of a three-
electron-bonded adduct followed by elimination of a hydroxide ion to yield a
sulfinyl radical as the reaction product [52, 53]. The formation of a sulfinyl
radical in the oxidation of thiols by superoxide has also been supported by ab
initio molecular orbital theory [52]. The disulfide was the only product in the
reaction of N -acetylcystein with O •− , studied by steady-state radiolysis [49].
Phe was the least reactive compound among aromatic amino acids at
alkaline pH ( k = (3.6 ± 0.5) × 10 −1 /M/s). His had a rate constant of 1.0 ± 0.2/M/s
in the alkaline pH range. The rate constants of Tyr and Trp were
(1.0 ± 0.2) × 10 1 /M/s and (2.4 ± 0.3) × 10 1 /M/s, respectively, in the alkaline pH
range. These results suggest that the aromatic ring(s) in Tyr and Trp influenced
reactivity with O •− .
A number of studies on the kinetics of superoxide with biological molecules
such as ascorbic acids, vitamin E, Trolox, catalase, MPO, and horseradish per-
oxidase have been summarized and reviewed [19, 25]. Studies involving metal
complexes and O •− have been performed to understand the role of metals in
the deleterious effects of superoxide in biological systems [19, 54-56]. The
reactions between cu 2+ -amino acid complexes with HO /O
2

2

• •− are of interest
because many of such copper complexes possess significant catalytic efficiency
to disproportionate superoxide radicals [19, 57]. For example, a study on the
reactivity of cu 2+ -histidine complexes in the pH range from 1 to 10 showed
that one of the complexes, (cuHist 2 H) 3+ , out of possible six complexes was
catalytic active [58]. The reaction of cu 2+ -arginine complexes with superoxide
in the pH range of 2.5-11.0 also supported the catalytic effect of copper

2