Chemistry Reference
In-Depth Information
1.3.2 Oxygen Species
ROS play fundamental roles in maintaining health and in developing diseases,
and estimation of their generation in isolated mitochondria has been evalu-
ated as 0.1-2.0% of all consumed oxygen [204]. Mitochondria can produce
O
−•
at complex I (NADH-coenzyme Q reductase) and complex III (ubiquinone-
cytochrome
c
oxireductase) [13, 205]. The generation of ROS in mitochondria
is monitored by NO
•
, which is transferred to other RNS (see Fig. 1.1). Thus, a
low concentration of NO
•
can increase the production of
O
−•
and H
2
O
2
, while
the formation of OONO
−
results in from the reaction of
O
−•
and NO
•
[206].
Other major cellular sources of ROS are lipoxygenases, Nox family of enzymes,
peroxisomers, uncoupled nitric oxide synthase (NOS), cyclooxygenases, xan-
thine oxireductase, and cytochrome P450 family proteins [207]. Levels of ROS
were shown to increase in mouse hepatic cells in culture and in mouse liver
by cytochrome P450 enzyme-mediated processes [208].
Significantly, the basic biology of cells and tissues is affected by SOD,
O
−•
,
and H
2
O
2
[209]. Due to the importance of SOD, several studies have been
performed on their structures and their involvement in the dismutation of
O
−•
[210-216]. MnSOD is an essential enzyme affecting levels of ROS in mitochon-
dria and the protection of cells from damage by ROS [210, 216]. Nickel super-
oxide dismutase (NiSOD) has also been studied to elucidate its role in the
disproportionation of
O
−•
[217-219]. Part of the
O
−•
produced in the mitochon-
dria may be converted to H
2
O
2
by Cu,Zn-SOD. The mechanistic aspects of the
reactions of SOD with
O
−•
are described in Chapter 4. Under unregulated
conditions, ROS accumulate and result in oxidative damage to cellular proteins,
lipids, and nucleic acids [5, 7, 220, 221]. However, SOD, CAT, and thiol-based
redox couples in molecular systems neutralize threats from ROS to cells.
Chapter 4 discusses the oxidation of functional groups on proteins by ROS
(
O
−•
,
1
O
2
, O
3
, and
•
OH). Mechanisms of reactions are also given in Chapter 4.
Carbonate radical (
CO
•−
) may also be considered as ROS due to its selectiv-
ity. The reactivity of
CO
•−
with amino acids is less than that of
•
OH, but it is
more selective and may also be a mediator of protein modification in cellular
environments under conditions of oxidative stress. Carbonate radicals may
also play a role in the decomposition of peroxynitrite in the presence of bicar-
bonate. Reactions of
CO
•−
are discussed in Chapter 5. Modifications of pro-
teins by peroxymonocarbonate (
HCO
−
) and carboxy radical (
CO
•−
) are briefly
presented in Chapter 4. Other species that may also be considered ROS are
peroxyl (ROO
•
) and alkoxyl (RO
•
) radicals, which are formed from the reac-
tion of carbon-centered radicals with oxygen. Peroxidation has been demon-
strated to go through chain reactions and to generate these radicals. The
breakdown of these radicals into carbonyl hydrperoxides, alcohols, and car-
bonyl groups suggests their importance in biological systems.
Sulfite and sulfate radicals (
•
SO
3
and
SO
•−
) may be other ROS because of
their possible reactions with amino acids and peptides (Chapter 5).
SO
•−
is a
−
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