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* |
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Oxygen 3 O2•A di-RADICAL |
How ROS is Formed from Oxygen |
Major Source (s) in Body |
Products Generated |
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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
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3 O2 is reduced by addition of 2 e's to outer shells |
Dismutation of O2•- O2•- + O2•- + 2H+ → H2O2 + 1O2*
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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+ |
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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-)
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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 |
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)
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Produce Peroxyl ROO• /Alkoxyl Radicals RO• Vital for killer action |
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Ozone O3 |
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O2•- as intermediate to OH•;
Peroxide anionO2 2-;
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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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