Biomedical Engineering Reference
In-Depth Information
Fig. 1 Biologically relevant
ROS production
2.1 Superoxide (O
2
2
)
In cells, the mitochondrial oxidation-reduction system generates superoxide
(O
2
-
). Specifically, enzymes such as NADH/NADPH oxidase, xanthine oxidase,
lipooxygenase, mitochondrial oxidase and cyclooxygenase reduce molecular O
2
during oxidative phosphorylation for ATP generation (Eq.
1
)[
9
]. Approximately
2 % of the O
2
reduced by mitochondria is converted into O
2
-
.O
2
-
is also gen-
erated in vivo by phagocytic cells such as macrophages, monocytes, neutrophils,
and eosinophils in response to foreign bodies such as bacteria [
10
].
O
2
þ
e
!
O
2
ð
1
Þ
Due to its negative charge, O
2
-
cannot readily cross biological membranes.
However, aqueous O
2
-
at low pH forms hydroperoxyl radical (HO
2
), which can
easily enter the cell. Superoxide is removed from cells by a spontaneous dismu-
tation reaction (Eq.
2
), during which two O
2
-
are converted to molecular oxygen
and hydrogen peroxide. The reaction rate constant is 8 9 10
4
M
-1
s
-1
, and the
reaction proceeds four orders of magnitude faster in the presence of the enzyme
superoxide dismutase [
11
,
12
]. Most of the biological effects of superoxide are
mediated through the dismutation to hydrogen peroxide.
O
2
þ
O
2
þ
2H
þ
!
H
2
O
2
þ
O
2
ð
2
Þ
2.2 Singlet Oxygen (O
2
(
1
D
g
))
Molecular oxygen exists in the triplet state ((
3
R
g
-
)
3
O
2
), with two unpaired elec-
trons of parallel spin in separate orbitals. Singlet oxygen is the electronically
excited state of oxygen when these electrons adopt antiparallel spins and occupy
the same orbital, thus opening an opportunity to accept electrons of either spin
[
10
]. Singlet oxygen is formed in cells by energy transfer from photochemically
excited photosensitizers to triplet state molecular oxygen or during an inflamma-
tory reaction. For example, O
2
-
produced by NADPH oxidase (Eq.
3
) undergoes
dismutation to form H
2
O
2
and O
2
(Eq.
4
). This H
2
O
2
is in the singlet state if
dismutation is spontaneous rather than catalyzed by superoxide dismutase. H
2
O
2
produces hypochlorite in the presence of myeloperoxidase (Eq.
5
) which in turn
reacts with H
2
O
2
to yield O
2
(
1
D
g
) (Eq.
6
).
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