Chart of ROS and their Metabolites in
the Body
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O2•-and
H2O2
- are primary reactive metabolites
of oxygen
OH•
,
LOO•,
LO•
- are produced by secondary reactions of the primary metabolites.
O2•-
is far less damaging than
H2O2,
which penetrates membranes andcan be transformed to
OH•,
HOCl,
1O2* |
Oxygen 3 O2•
 
A di-RADICAL
|
How
ROS is Formed from Oxygen |
Major
Source (s) in Body |
Products Generated |
|
Superoxide
RADICAL
O2•-
MildlyReactive
Can not easily get into cells |
3O2
is reduced by addition of 1 electron to outer shells |
Electron leakage from mitochondrial Electron Transfer Chain:
3
O2•
+e-
→
O2•-
Phagocytic respiratory burst
(uses NADPH-dependent Oxidase):
NADPH +2O2
→NADP +
O2•-+
H2O2
Phagocytes also produce:
OH•
1O2*
NO* ONOO- |
Dismutation of
O2•-
O2•-
+
O2•-
+ 2H+
→
H2O2
+
1O2
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|
Haber-Weiss Reaction - As reductant of free transition metals:
E.g. iron-catalyzed
(1)
O2•-
+ Fe3+
→
3
O2•
+ Fe2+
(2) Fe2+
+
H2O2
→Fe3+
+
OH•+OH—
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H2O2
Poorly
Reactive
NON-radical
 Passes
easily into cells (because it is neutrally charged) |
3
O2
is reduced by addition of 2 e's to outer shells |
Dismutation of
O2•-
O2•-
+
O2•-
+ 2H+
→
H2O2
+
1O2*
|
Haber-Weiss Reaction (2) /
Fenton Reaction
- Main source ofOH•
in presence of free transition metals:
E.g.
Iron-catalyzed
(2)
H2O2+Fe2+
→
OH•+
OH—+Fe3+ |
|
Production of
HOCl by neutrophils:
H2O2
+Cl-→
HOCl +OH—
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|
1O2*
With
hypochlorite or peroxynitrite
H2O2
+ ClGAS →
1O2*+ClGAS +H2O
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Hydroxyl
RADICAL
OH•
Most potent biological oxidant |
By reduction of
H2O2
(i.e.
by addition of 1 e-)
|
Haber-Weiss Reaction:
O2•-
and
H2O2
in the presence of freetransition metals produce MOST
OH•:
E.g.
Iron-catalyzed
(1)
O2•-
+ Fe3+ →
3
O2•
+ Fe2+
(2) Fe2+
+
H2O2
→
Fe3++
OH•+OH—
Normally, most iron confined in RBCs
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O3and
H2O2
|
2
O3
+H2O2→
OH•
+3
O2•
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Radiation
|
Radiobiological damage
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Singlet oxygen
1O2*
Highly
Reactive
NON-radical
Lowest excited state of oxygen
Passes easily into cells
(because it is neutrally charged) |
TherapiesEnergy input (radiation)
to
3
O2
Sensitizer with light and oxygen.(Basis of
PDT
for cancer) |
"Excited"electron spin flips + jumps to next orbital
3
O2
•
+Energy
→
1O2*
Chlorophyll (in plants), retinal, flavins, dyes (Bengal rose, methylene
blue), natural pigment (porphyrins)
Sens
→Sens*
→
Sens +
1O2*
uvO2
Photosynthesis may occur in skin cells |
Transfer the energy to a new molecule -
thereby acting as a catalyst for free radical formation.
Reactions with substrate molecules -
leading to the formation of a new free radical by oxidation.
(Olefins,
dienes, sulphides, aromatics, hetero-aromatics, terpenes, steroids,
fatty acids, flavones, tetracyclines, vitamines, amino acids, proteins,
nucleic acids, blood and bile pigments, and synthetic polymers)
(1)
Ene reaction -
H abstraction/O2 addition
Lipid peroxidation:
RH+
1O2*
→
ROOH
Unsaturated lipid Hydroperoxide
(2)
Cycloaddition -
Typically results in:
1,2-dioxetaneorEndoperoxide
(3)Oxygenation - unfinished
1O2*
reacts
with ascorbate, producing H2O2
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Enzymatically
catalyzed
by
peroxidases
/lipooxigenasesor myeloperoxidase (MPO) - in neutrophils, monocytes, new
macrophages.
Or SOD
|
H2O2w/hypochlorite or peroxynitrite
H2O2
+ ClGAS →
1O2*
+ClGAS +H2O
HOCl
with
O2•-
(MPO-dependent):
HOCl
+
O2•-
→
Cl-
+
OH•
+
1O2*
HOCl
with
H2O2:
HOCl
+
H2O2
→
HCl +
H2O +
1O2*
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Dismutation of
O2•-
or
ROO•:
O2•-
+
O2•-
+
2H+
→
H2O2
+
1O2* (Non-catalyzed, rate pH-dependent)
O2•-
+
O2•-
+
2H+
→
H2O2
+
3O2 (Enzymatically w/SOD
very fast reaction)
ROO•
+
ROO•
+
2H+
→
RO•
+
1O2*
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Endogenously
|
Respiratory burst of phagocytes;
By-product of metabolism
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Thermo- decomposition of dioxetanes
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Phosphite ozonides:
(RO)3PO3
→ (RO)3PO
+
1O2*
Endoperoxides:
E.g. 9,10-diphenylanthracene peroxide (DAP)
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Hydroperoxides
(ROOH)/
Endoperoxides
|
React with some metal ions. |
Involves breaking C=C bonds E.g. in carotene, chlorophyll,
polyunsaturated fatty acids (PUFAs)
|
Produce Peroxyl
ROO•
/Alkoxyl Radicals
RO•
Vital for killer action |
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Ozone
O3 |
|
O2•-
as intermediate to
OH•;
Peroxide anionO2
2-;
|
O3
oxidizes/ionizes
organic molecules(saturated hydrocarbons, amines, sulfhydryl
groups and aromatic compounds) to chiefly aldehydes, ketones, acids or
alcohols.
O3
will oxidize metals
(except gold, platinum, and iridium) to metal oxides (much easier
to remove) -
2Cu2++2H++
O3→
2 Cu3++
H2O+O2
O3
changes oxides into peroxides:
SO2
+
O3
→
SO3 +
O2•
O3
converts cyanides into cyanates
(1000 X less toxic than
cyanide):
CN-
+
O3
→CNO- +
O2•
O3
→
1O2*
+
O1* Excited
singlet oxygen MOLECULE
1O2* Excited
oxygen ATOM
O1*
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 Chlorine
Dioxide
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