Superoxide dismutation

Many different kinds) Superoxide dismutation (eukaryotes)... 

Vitamin A (retinol) is not a classic antioxidant although it is frequently related to a group of antioxidant vitamins E, C, and A. Murata and Kawanishi [83] found that retinol and its derivative retinal induced the formation of 8-HOdG in HL-60 cells. This process was supposedly mediated by hydroxyl radicals formed from hydrogen peroxide (the product of superoxide dismutation) and endogenous transition metal ions. 

Superoxide-dismuting activity of copper rutin complex was confirmed by comparison of the inhibitory effects of this complex and rutin on superoxide production by xanthine oxidase and microsomes (measured via cytochrome c reduction and by lucigenin-amplified CL, respectively) with their effects on microsomal lipid peroxidation [166]. An excellent correlation between the inhibitory effects of both compounds on superoxide production and the formation of TBAR products was found, but at the same time the effect of copper rutin complex was five to nine times higher due to its additional superoxide dismuting capacity. 

Thus, the mechanism of MT antioxidant activity might be connected with the possible antioxidant effect of zinc. Zinc is a nontransition metal and therefore, its participation in redox processes is not really expected. The simplest mechanism of zinc antioxidant activity is the competition with transition metal ions capable of initiating free radical-mediated processes. For example, it has recently been shown [342] that zinc inhibited copper- and iron-initiated liposomal peroxidation but had no effect on peroxidative processes initiated by free radicals and peroxynitrite. These findings contradict the earlier results obtained by Coassin et al. [343] who found no inhibitory effects of zinc on microsomal lipid peroxidation in contrast to the inhibitory effects of manganese and cobalt. Yeomans et al. [344] showed that the zinc-histidine complex is able to inhibit copper-induced LDL oxidation, but the antioxidant effect of this complex obviously depended on histidine and not zinc because zinc sulfate was ineffective. We proposed another mode of possible antioxidant effect of zinc [345], It has been found that Zn and Mg aspartates inhibited oxygen radical production by xanthine oxidase, NADPH oxidase, and human blood leukocytes. The antioxidant effect of these salts supposedly was a consequence of the acceleration of spontaneous superoxide dismutation due to increasing medium acidity. 

The inhibition of lipid peroxidation by metalloporphyrins apparently depends on metal ions because only compounds with transition metals were efficient inhibitors. Therefore, the most probable mechanism of inhibitory effects of metalloporphyrins should be their disuniting activity. Manganese metalloporphyrins seem to be more effective inhibitors than Trolox (/5o = 204 pmol I 1) and rutin (/50 112 pmol I 1), and practically equal to SOD (/50= 15 pmol I 1). The mechanism of inhibitory activity of manganese and zinc metalloporphyrins might be compared with that of copper- and iron-flavonoid complexes [167,168], which exhibited enhanced antiradical properties due to additional superoxide-dismuting activity. 

The mechanisms of superoxide-dismuting activity of SODs are well established. Dismutation of superoxide occurs at copper, manganese, or iron centers of SOD isoenzymes CuZnSOD, MnSOD, or FeSOD. These isoenzymes were isolated from a variety of sources, including humans, animals, microbes, etc. In the case of CuZnSOD, dismutation process consists of two stages the one-electron transfer oxidation of superoxide by cupric form (Reaction (1)) and the one-electron reduction of superoxide by cuprous form (Reaction (2)). 

The mechanism of catalytic superoxide dismutation by nitroxides can be presented as follows [27] ... 

Many copper(II) complexes, including Cu(DIPS)2 (DIPS = diisopro-pylsalicylate), Cu(salicylate)2, and Cu(Gly-His-Lys), are also active in superoxide dismutation (437, 438), but their use in vivo is limited by dissociation of Cu(II) and binding to natural ligands such as albumin (439). In contrast, the activity of Fe-93 is not affected by albumin (439, 440). 

Unlike Cu(II), free Mn(II) ions are not active in superoxide dismutation, but some Mn(II)-macrocycle complexes catalyze the dismutation of 02 and are biologically active (441). For example, complex 94 (SC-52608) inhibits neutrophil-mediated killing of human aortic endothelial cells in vitro, attenuates inflammation, protects against myo-... 

II. Catalytic Superoxide Dismutation by Seven-Coordinate Manganese and... 

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. 

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