REACTIVE INORGANIC OXY-SPECIES OF C, N, S, AND P - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 206

O 2 •-

• NO

2H + /e -

O 2

ONOO -

• NO 2

H 2 O 2

CO 2 /
HCO 3 -

BH
P-Fe(III)

H + e -

• NO

B • HOOCO 2 - [ONO •• OCO 2 - ] NO 2 - ONO •• OH N 2 O 3

BH
BNO

M n +
(XO/SOD?)
M ( n +1)+

P-Fe(III)/
H 2 O 2

BH

HCO 3 -
BOH

OH -

CO 3 •-

• NO 2 • OH • NO 2 • NO 2 • NO 2 -

BOH

B—B

BNO

BNO 2
Oxidative Damage

Figure 5.1. Schematic representation of sources and consequences of oxidants derived
from bicarbonate buffer. The reactions were not balanced and some intermediates were
omitted for clarity. xO, SOd and P-Fe(III), BH, and M n+ represent xanthine oxidase,
superoxide dismutase 1, hemoproteins in the iron(III) state, general biomolecule, and
transition metal ion, respectively (adapted from Medinas et al. [2] with the permission
of IUBMB).

5.1 CARBON SPECIES

5.1.1 Carbonate Radical

5.1.1.1 Generation and Properties. The peroxidase activity of the mutated
superoxide dismutase 1 (SOd-1) is one possibility of the production of the
carbonate radical ( CO •− ). The proposed mechanism given in Figure 5.2 com-
bines the results and suggestions of several studies [2, 11-14]. The reaction of
SOd-1 with H 2 O 2 proceeds in steps, which ultimately forms an enzyme-bound
oxidant (e.g., Cu(O) ↔ Cu(OH • ) 2+ ↔ Cu 3+ ) at the enzyme active site [15].
The oxidation of one or more histidine residues at the SOd-1 active site is
promoted by this oxidant [16]. Formation of the hypothetical complex of
Cu(I)-hydrogen peroxide in the mechanism reacts with CO 2 to form an
enzyme-Cu(I)-bound peroxymonocarbonate ( HCO − ), which reduces to
produce a diffusible CO •− (Fig. 5.2). The enzyme is recycled to the Cu(II) state.
The formation of the complex is supported by the accelerating effects of the
bicarbonate buffer on the oxidations of transition metal ions and enzyme-
metal centers [17-20]. The formation of peroxymonocarbonate as a feasible