Chemistry Reference
In-Depth Information
Figure 1.8.
Oxidation of protein thiols by one-electron and two-electron pathways.
PUFA, polyunsaturated fatty acids (adapted from Winterbourn and Hampton [230]
with the permission of Elsevier Inc.) See color insert.
sulfoxide through a one-electron transfer [232]. Recently, the reactivity of
simple thiols and protein thiols with H
2
O
2
has been explained in detail [228].
Generally, the nucleophilic attack of thiolate on an electrophile occurs and
rate constants vary by seven orders of magnitude (
k
(cysteine)) = 2.6 × 10
1
/M/s;
k
(peroxiredoxin 2) = 1.0 × 10
8
/M/s) [233, 234]. Thiyl radicals are involved in
enzymatic and detoxifying pathways, and in recent years, the oxidizing power
of the thiyl radicals produced by one-electron oxidations has been studied. In
a recent work, cysteine thiyl radicals were shown to be involved in reversible
intramolecular hydrogen transfer reactions with amino acid residues in pep-
tides and proteins [235].
The reduction potential is the key parameter to express oxidation power
and is pH dependent. The reduction potential of a one-electron couple,
expressed as a midpoint electrode potential,
E
m
(GS
•
, H
+
/GSH) for GSH (γ-
glutamylcysteineglycine) in water as a function of pH has been determined
(Fig. 1.9) [236].
E
m
is an experimentally useful midpoint potential where
the sum of concentrations of oxidants is equal to the sum of reductants [237].
In Figure 1.9, the solid line is for a simple thiol in which only thiol/thiolate
ionization was considered with p
K
a
= 9.2 and assuming
E
o
(RS
•
/RS
−
) = 0.8V.
However, the dashed line represents the considered four macroscopic p
K
a
values of the reductant (GSH, p
K
r1−4
), consisting of 2.05, 3.40, 8.72, and 9.49,
and three p
K
a
values of the oxidant (GS
•
, p
K
o1-3
), consisting of 1.8, 3.2, and
9.08, and also assuming
E
o
(RS
•
/RS
−
) = 0.8V for the fully deprotonated GSH
[236]. The value of
E
m
(GS
•
, H
+
/GSH) = 0.92 at pH 7.4 was determined and
compared to other biologically relevant free radicals (Table 1.7). The value of
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