Reactions of superoxide anion

Despite their increasing biological importance, reactions of superoxide anion and of its acidic form, hydroperoxyl radical, with proteins, are little understood. More generally speaking, the chemical basis of biological role of superoxide is still questioned (88). 

It is known that superoxide reacts very slowly with all amino-acids since all rate constants are below 100 mol l 1 s (89). Hence its reactivity with proteins without prosthetic group is low (89). One exception seems to be collagen, in which proline residues are oxidized into hydroxyproline (90). On the other hand, superoxide reacts efficiently with free radicals such as tryptophanyl radical (91). Reaction is fast with metalloproteins. It proceeds mostly by oxidizing or reducing the metal center. Some characteristics and rate constants of reactions with metalloproteins are given in table 7. It is obvious that products are often unknown and that the mechanism is sometimes unclear. It seems that there is no reaction with transferrin (92) and horseradish and lacto-peroxidase compounds II (93). The reason is unknown. 

Superoxide ion reduces Fe3+-cytochrome c (k = 2.6 xlO mol l 1 S (97)) but can also oxidize Fe2+-cytochrome c. The free radical seems to attack one of the edges of the heme and the kinetic control is due to electrostatic guidance to the heme. 

Brownian dynamics simulation suggests that such a high value is due to an enhanced substrate attraction by the modified electric field distribution. The reaction with Mn SOD was less deeply studied. The proposed mechanism involves adducts Mn2+(02 ) (114). 

INSIGHT INTO MECHANISMS REACTIONS OF OTHER FREE RADICALS 

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The elementary reaction step, which involves the formation of singlet oxygen, is a reaction of superoxide anion radicals CO ), which are the reaction intermediates of the above oxidation when performed in an alkaline medium. In the presence of water they may be converted to hydrogen peroxyl radicals HOO as follows ... 

Shimizu N, Kobayashi K, Hayashi K (1989) Kinetics of the reaction of superoxide anion with ferric horseradish peroxidase. Biochim Biophys Acta 995 133-137... 

Reactions of Superoxide Anion Radical and Hydrogen Peroxide. 195... 

The interesting cage reactions of superoxide anion subsequent to the reaction of O2 in the absence of a salt have been reviewed in the preceding section. 

DISMUTATION REACTION OF SUPEROXIDE ANIONIC RADICALS (SCHAAP.A.R)... 

Recently it has been reported,that singlet oxygen can be produced by the dismutation reaction of superoxide anionic radicals (see chemical generation of singlet oxygen,page 3 of this paper)(31-33) Superoxide anionic radicals take part in several polymer reactions and are also important species in biopolymer chemistry ... 

Fig. 3. Production of reactive species. (A) ROS can be produced from the weak radical oxygen in the mitochondria and endoplasmic reticulum, by various enzymatic reactions, and from oxyhemoglobin. Normally, nontoxic hydrogen peroxide can give rise to the powerful hydroxyl radical in the presence of transition metals (R5). Oxygen can also be induced to react with biomolecules by transition metals and enzymes. RNS can be produced by reaction of superoxide anion radical with the weak radical nitric oxide. These can react to form the powerful oxidant peroxynitrite/peroxynitrous acid, which can cause formation of other radicals, some with longer lives. See the text for details. SOD, superoxide dismutase. (B) Myeloperoxidase in leukocytes can produce the reactive species hypochlorous acid and tyrosyl radical. Unpaired electrons are indicated by the dense dots and paired electrons by the light ones.

Korytowski W, Kalyanaraman B, Menon lA, Sama T, Scaly RC (1986) Reaction of Superoxide Anions with Melanins Electron Spin Resonance and Spin Trapping Studies. Biochim Biophys Acta 882 145... 

The reaction of superoxide anion with a copper(ii) complex has been reported. Pale blue solutions of [Cu(phen)2] + in DMSO react with O2 on mixing to yield deep brown solutions of [Cu(phen)a]+. The copper(i) species reacts only relatively slowly with dissolved oxygen in this solvent but the reaction is dramatically accelerated by protons. The overall equilibria are... 

Valentine JS, Curtis AB (1975) A convenient preparation of solutions of superoxide anion and the reaction of superoxide anion with a copper (II) complex. J Am Chem Soc 97 224-226... 

At pH values below 4.7— the pATa of HO2 —disproportionations of 02 and HO2 were orders of magnitude slower than reactions of superoxide anion or its protonated form with a second equivalent of POMie. This was true even at the lowest pH values studied, at which disproportionations of superoxide (and of... 

V. Massey, S. Strickland, S.G. Mayhew, L.G. Howell, P.C. Engel, R.G. Matthews, M. Schuman, and P.A. Sullivan, Production of superoxide anion radicals in the reaction of reduced flavins and flavopro-teins with molecular oxygen. Biochem. Biophys. Res. Commun. 36, 891-897 (1969). 

Other postulated routes (Jourd heuil et al., 2003) to RSNO formation include the reaction between NO and 02 to yield N02 via a second-order reaction. NO and thiolate anion, RS, react giving rise to thiyl radical, (RS ) [e]. RS then reacts with NO to yield RSNO [f]. The reaction between RS and RS- can also be the source of non-enzymatic generation of superoxide anion (02 ) [g], [h]. 02 reacts with NO to produce peroxynitrite (ONOO ) [i] (Szabo, 2003). Thiols react with ONOOH to form RSNOs [k] (van der Vliet et al.,1998). 

A photooxidative reaction in which molecular oxygen is incorporated into the reaction products(s). Three mechanisms appear to be common for such processes (a) reaction of triplet O2 with free radicals that have been generated photochemically (b) reaction of photochemically produced singlet oxygen with a molecular species and (c) the production of superoxide anion which then acts as the reactive species. See also Photooxidation... 

The T)/pe I reaction often results in the formation of superoxide anion via electron transfer from the excited triplet PS to molecular oxygen. Though superoxide is not particularly damaging to the cell, it can react with itself, producing hydrogen peroxide and oxygen in the enzymatic reaction catalyzed by superoxide dismutase, or it can produce highly reactive hydroxyl radical (HO ). 

The direct reaction of superoxide with nitric oxide is only one of at least four possible pathways that can form peroxynitrite (Fig. 40). For example, superoxide should also efficiently reduce nitrosyldioxyl radical to peroxynitrite. Alternatively, nitric oxide may be reduced to nitroxyl anion, which reacts with oxygen to form peroxynitrite. Superoxide dismutase could even catalyze the formation of peroxynitrite, since reduced (Cu or cuprous) superoxide dismutase can reduce nitric oxide to nitroxyl anion (Murphy and Sies, 1991). Thus, superoxide might first reduce superoxide dismutase to the cuprous form, with nitric oxide reacting with reduced superoxide dismutase to produce nitroxyl anion. A fourth pathway to form peroxynitrite is by the rapid reaction of nitrosonium ion (NO" ) with hydrogen peroxide. This is a convenient synthetic route for experimental studies (Reed et al., 1974), but not likely to be physiologically relevant due to the low concentrations of hydrogen peroxide and the difficulty of oxidizing nitric oxide to nitrosonium ion. 

The enzyme copper, zinc superoxide dismutase (Cu,Zn-SOD, EC 1.15.1.1) catalyzes the disproportionation of superoxide anion to dioxygen and hydrogen peroxide (equations 1 and 2). Crystallographic data can be found in References 41-46. This antioxidant enzyme is present in the cytosol and mitochondrial intermembrane space of eukaryotic cells and in the periplasmic space of bacterial cells as a homodimer of 32 kDa. Each monomer binds one copper and one zinc ion. The reaction mechanism involves the... 

The evidence for this reaction is that when solutions of hemoglobin are subjected to a flux of superoxide anions generated either photochemically or by radio-... 

Hydrogen abstraction by RH02 could also participate in the process of initiating a chain of thermal oxidation reactions (pathy). In aqueous systems, cations will further react by solvolysis, and superoxide anion will readily disproportionate to yield H202 (path i). This is in contrast to the fate of superoxide anions in ozonation advanced oxidation processes (AOPs), where they react primarily with ozone to produce hydroxyl radical. This description of the chemical pathways of UV/H202 oxidation of organics illustrates that, when oxygen is present, the major paths directly or indirectly create more... 

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