Superoxide dismutase Dismutation

Section 5.2.3 in Chapter 5. Superoxide dismutase enzymes catalyze dismutation of the superoxide anion radical (O2 ) according to the summary reactions in equation 7.1 ... 

Mn superoxide dismutases are found in both eubacteria and archaebacteria as well as in eukaryotes, where they are frequently found in mitochondria. They (Figure 16.1) have considerable structural homology to Fe SODs both are monomers of 200 amino acid and occur as dimers or tetramers, and their catalytic sites are also very similar. They both catalyse the two-step dismutation of superoxide anion and, like the Cu-Zn SODs, avoid the difficulty of overcoming electrostatic repulsion between two negatively charged superoxide anions by reacting with only one molecule at a time. As in the case of Cu-Zn SOD, a first molecule of superoxide reduces the oxidized (Mn3+) form of the enzyme, releasing... 

ROS generation is generally a cascade of reactions that starts with the production of superoxide. Superoxide rapidly dismutates to hydrogen peroxide either spontaneously, particularly at low pH, or catalyzed by superoxide dismutase (SOD). 

Thus, superoxide can react with almost all redox-active metal centers (Scheme 1). In general, going through similar redox reaction steps metal complexes can interact with superoxide either as catalysts for its dismutation (superoxide dismutase (SOD) mimetics), or in a stoichiometric manner (Scheme 1). 

A superoxide dismutase activity had been reported for the Fe-EDTA complex in contrast with the inactivity of the Cu-EDTA complex. It was shown, on the contrary, that Fe-EDTA, instead of catalysing the dismutation of OJ, interferes with the reduction of nitroblue tetrazolium and of Fe(III)-cytochrome c in the assays of the dismutase activity... 

The demonstration that PMNs formed O2- in the respiratory burst necessitated the consideration of all the species which result when dioxygen is reduced one electron at a time (Fig. 1). Superoxide, the result of the reduction of dioxygen by one electron, appears to act mainly as a mild reductant in aqueous solutions. But when it coexists with H2O2, its spontaneous dismutation product, O can initiate a number of potentially injurious events [reviewed by Fridovich The primary means by which cells deal with superoxide anions appears to be through the catalysis of their dismutation by a family of metalloenzymes collectively designated superoxide dismutases. 

Mammalian systems have enzymes, superoxide dismutases (SODs), which dismutate two molecules of superoxide into one of hydrogen peroxide and one of oxygen. The enzymes are located in the cytosol and mitochondria. The location in the mitochondria is important because ROS are often produced there, and one form of SOD is inducible, as a result of oxidative stress. 

In this reaction (demonstrated in vitro), one of the two radicals is oxidizing while the other is reducing. In vivo, this reaction is catalyzed by one of several isoforms of an enzyme known as superoxide dismutase (SOD). As shown above, hydrogen peroxide may form as a result of the superoxide anion s dismutation reaction however, it may also be produced from a bivalent reduction of 02. The addition of the second electron leads to the formation of hydrogen peroxide, which is a powerful oxidizing agent. Due to the unpaired electrons in their outer shells, free radicals are favored to pair with other molecules during bimolecular collisions. 

Superoxide dismutase is an enzyme which catalyses the dismutation of superoxide into 02 and H202 (Valentine and Pantoliano, 1981 Oberley, 1982 Bannister et al., 1987) 202 + 2H + - H202 + 02... 

The generation of the superoxide anion radical is but the first of four steps in the complete reduction of oxygen to water. Successive steps include the sequential generation of hydrogen peroxide, formed through the dismutation of superoxide via superoxide dismutase (SOD), and the hydroxyl radical. The hydroxyl radical is one of the most powerful and most reactive oxidants that exist. It reacts immediately... 

HP here is great interest in the biochemistry and relevant coordination chemistry of copper-containing proteins (1,2, 3, 4, 5). They are widely distributed in both plants and animals and are often involved in oxygen metabolism, transport, and use. One of the most actively studied copper proteins is bovine erythrocyte superoxide dismutase (SOD) (6,7,8). This enzyme catalyzes the dismutation of superoxide ion, Reaction 1. 

Some metal- (especially copper) complexes catalyse the dismutation of superoxide at rates that compare favourably with catalysis by superoxide dismutase. One could therefore argue that the presence of such complexes in vivo might be beneficial. There are, however, additional considerations (1) such metal complexes may also reduce hydrogen peroxide, which could result in the formation of hydroxyl radicals, and (2) it is extremely likely that the metal will be displaced from its ligands (even when those ligands are present in excess), and becomes bound to a biomolecule, thereby becoming less active as a superoxide dismutase mimic. As an example, copper binds well to DNA and catalyses the formation of hydroxyl radicals in the presence of hydrogen peroxide and ascorbate [30],... 

The reduction of oxygen by copper(I) is faster than that of the iron(II) complexes 5x 104M 1 s-1 for CuI(phen)2 [52] and 4xl04M 1 s 1 for Cu1 (histidine [76]. It is this relatively fast autoxidation that limits the usefulness of copper complexes as mimics of superoxide dismutase under conditions of high superoxide concentrations [77]. Copper(II) catalyses the dismutation of superoxide at near diffusion-controlled rates kcat = 8 x 109 M 1 s-1 [78,79],... 

In 1969, McCord and Fridovich discovered that a copper-containing protein, erythrocuprein, isolated from red blood cells, catalyzed the dismutation of superoxide O - [17]. This enzyme was renamed superoxide dismutase (SOD). A striking positive correlation is now known to exist between the life-span potential of mammal species and the ratio of SOD activity and specific metabolic rate of their tissues [18]. The ubiquitous vitaminE, glutathione peroxidases and superoxide dismutases provide a primary protective barrier against the toxicity of free radicals and peroxides in mammalian cells. 

The redox-active copper of copper/zinc-superoxide dismutases [24,37] is associated with an E° for [Cun/Cur] of +0.3-0.4 V, approximately mid-way between the redox potential E° aq for O2 reduction to 02 relative to 1M 02, and that for 02 reduction to H2O2, enabling dismutation to take place. 

The reaction products of superoxide ions are believed to be partly responsible for the removal and destruction of bacteria and damaged cells [1]. In view of its low reactivity it is unlikely that superoxide itself is responsible for killing the invading material, but the hydrogen peroxide formed from dismutation by superoxide dismutase can kill some strains of bacteria. Once the phagocytic... 

There are a number of enzymes that catalyse the dismutation of superoxide in vivo, viz. the superoxide dismutases [50,51], They are metalloproteins which contain copper, zinc, manganese or iron as the prosthetic group. The enzyme catalase exists in vivo to degrade hydrogen peroxide within cells to form water and oxygen [43]. As stated earlier, there are barely detectable amounts of these two enzymes in the synovial fluid of arthritic patients and hence both superoxide radicals and hydrogen peroxide are potential mediators of damage to the biomolecules of the synovial fluid. 

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