Superoxide dismutating enzymes

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 ... 

The pH dependence of the Mn(III/II) potential has not been studied for other organisms. It is interesting to note that the Fe-substituted form of MnSOD has E° = —0.24 V and that the Mn-substituted form of FeSOD has E° > 0.96 V [105]. These altered enzyme forms are ineffective in superoxide dismutation. 

Other than in prokaryotic cells which lack mitochondria and chloroplasts, manganese superoxide dismutases are apparently restricted to the above two organelles in eukaryotic cells (51, 52) this forms strong support for the symbiotic hypothesis for the origin of mitochondria and chloroplasts (53, 54). Kinetic studies of superoxide dismutation by these enzymes indicate three oxidation states of Mn (presumably divalent, trivalent, and tetravalent) are involved in the catalytic cycle (57, 58). They also show that a Mn-02 complex may conceivably be formed. Well-characterized Mn-dioxygen (i.e., 02,02 , 022 ) adducts are extremely rare, the first structurally characterized example being reported only in 1987 (60). 

Superoxide dismutase (SOD, EC 1.15.1.1) is a scavenger of the superoxide anion, and therefore, provides protection against oxidative stress in biological systems [259]. Most SODs are homodimeric metalloenzymes and contain redox active Fe, Ni, Mn or Cu. The superoxide dismutation by SOD is among the fastest enzyme reactions known. The rate constant for CuZnSOD is = 2x 10 s [260], FeSOD is about one order of... 

For molecular electrocatalysts otherwise, and especially transition metal macrocycles, the electrocatalytic activity is often modified by subtle structural and electronic factors spanning the entire mechanistic spectrum, that is, from strict four-electron reduction, as for the much publicized cofacial di-cobalt porphyrin, in which the distance between the Co centers was set at about 4 A [12], to strict two-electron reduction, as in the monomeric (single ring) Co(II) 4,4, 4",4" -tetrasulfophthalo-cyanine (CoTsPc) [20] and Co(II) 5,10,15,20-tetraphenyl porphyrin (CoTPP) [21]. Not surprisingly, nature has evolved highly specific enzymes for oxygen transport, oxygen reduction to water, superoxide dismutation and peroxide decomposition. 

Copper is present in a large number of enzymes, many involved in electron transfer, activation of oxygen and other small molecules like oxides of nitrogen, methane and carbon monoxide, superoxide dismutation, and even, in some invertebrates, oxygen transport (for further details see Granata et al., 2004 Hatcher and Karlin, 2004 Messerschmidt et al., 2001 Rosenzweig and Sazinsky, 2006 Solomon, 2006). 

Fig. 55. Reaction scheme of superoxide dismutation following the bovine enzyme numbering. The first O2 molecule binds to Cu(II) and is stabilized by the H bond to Arg-141. A second superoxide molecule then approaches the active site and, by an outer-sphere electron transfer via the Cu-bound first O2 molecule, reduces the copper to Cud) 44) (step III). Alternatively, O2" directly reduces superoxide to peroxide 336) (step IV), leaving as dioxygen. Note that the Cu(I)-superoxide and Cu(II)-peroxide complexes are resonant forms of the same molecular arrangement. The newly formed peroxide is protonated by Arg-141 and leaves as HO2. Arg-141 receives a proton from the solvent, restoring the active enz5Tne (I). These reaction proposals do not require the breaking and reforming of the Cu-His-61 bridge.

The superoxide dismutation can be spontaneous or can be catalyzed and therefore significantly accelerated by the enzyme superoxide dismutase (SOD). The superoxide not only generates lydrogen peroxide (H2O2) but also stimulates its conversion into OH radicals, which are actually extremely strong oxidizers very effective in sterilization through a chain oxidation mechanism (to be especially discussed in Section 12.1.5). The H2O2 conversion into OH, known as the Fenton reaction, proceeds as a redox process provided by oxidation of metal ions (for example, Fe +) ... 

Besides the superoxide dismutation mechanism, the reactivity of metal centers, in particular manganese complexes, toward NO is very much dependent on the possibility for binding a substrate molecule. As it will be shown later, the possibility that MnSOD enzymes and some mimetics can react with NO has been wrongly excluded in the literature, simply based on the known redox potential for the (substrate) free enzymes, mimetics, and NO, respectively. Therefore, the general fact that, upon coordination, redox potentials of both the metal center and a coordinated species are changed should be considered in the case of any inner-sphere electron-transfer process as a possible reaction mechanism. 

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... 

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