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H
2
O
2
R
•
+ HCO
3
-
RH
SOD-Cu(II)
H
+
+ HOO
-
CO
3
•-
+ HO
-
NH
+
NH
+
GIu
O
Arg
C
O
SOD-Cu(I)
H
HO
O
His
Cu
+
SOD-Cu(I)
His
His
H
H
+
+ HOO
-
CO
2
+ H
2
O
-
O
O
SOD-Cu(I)
H
2
O
2
H
+
+ HCO
3
-
Figure 5.2.
Mechanism proposed for carbonate radical production during the peroxi-
dase activity of superoxide dismutase 1. The inset shows a pictorial view of the enzyme-
Cu(I)-bound peroxymonocarbonate intermediate (adapted from Medinas et al. [2]
with the permission of IUBMB). See color insert.
biological oxidant was suggested earlier [21, 22]. A xanthine oxidase (xO)
turnover process involving peroxymonocarbonate as the precursor of
CO
•−
has also been proposed (see below).
xO, a complex enzyme, consists of two identical subunits each composed
of one molybdenum atom, one of flavin adenine dinucleotide (FAd), and two
nonidentical iron sulfur centers [2]. The generation of
CO
•−
by xO through
the Fenton reaction was first proposed in the 1970s to explain the detection
of low-level chemiluminescence from incubations of xO, acetaldehyde, and
bicarbonate at pH 10.2 [23]. Recently, electron paramagnetic resonance (EPR)
measurements provided strong evidence for the production of the
CO
•−
radical
in the xO-mediated oxidation of xanthine, acetaldehyde, and hypoxanthine at
pH 6.9-8.1 [1, 13, 22, 24]. A generalized scheme was proposed based on the
many redox centers of xO involved in the electron flow from the oxidizing
species to result in the production/escape of the intermediates, which are par-
tially protonated/reduced, such as
HO
−
and
O
•−
(Fig. 5.3). The
HO
−
anion may
react with the surrounding CO
2
to produce peroxymonocarbonate. This species
is then reduced at the active site to
CO
•−
(Fig. 5.3). Another possibility is the
peroxymonocarbonate leaves the active site and behaves as a two-electron
oxidant.
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