Superoxide dismutase catalysis

Cytocupreins (EC 1.15.11) Erythrocuprein Cerebrocuprein Hepatocuprein Erythrocytes Brain Liver 31-33 2 Blue-green Superoxide dismutase Catalysis of dismutation of Each molecule also contains 2 atoms of zinc... 

Cockle, S. A., Bray, R. C. Do all the copper atoms in bovine superoxide dismutase function in catalysis In Superoxide and Superoxide Dismutases (Michelson, A. M., McCord, J, M., Fridovich, L, eds.), London-New York-San Francisco, Academic Press, 1977, pp. 215-216... 

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. 

Dopa can also undergo autocatalytic oxygenation with Fem, but Cu11 inhibits the reaction. This difference in reactivity reflects different coordination modes (see Section 20.2.2.2.8).82 The enzyme superoxide dismutase (vide infra) catalyzes disproportionation of the superoxide ion. The same catalysis is exhibited by Cun-L-His solutions, the reactive species, from the pH dependence, appearing to be [Cu(L-HisO)(L-His)]+. 

Copper has an essential role in a number of enzymes, notably those involved in the catalysis of electron transfer and in the transport of dioxygen and the catalysis of its reactions. The latter topic is discussed in Section 62.1.12. Hemocyanin, the copper-containing dioxygen carrier, is considered in Section 62.1.12.3.8, while the important role of copper in oxidases is exemplified in cytochrome oxidase, the terminal member of the mitochondrial electron-transfer chain (62.1.12.4), the multicopper blue oxidases such as laccase, ascorbate oxidase and ceruloplasmin (62.1.12.6) and the non-blue oxidases (62.12.7). Copper is also involved in the Cu/Zn-superoxide dismutases (62.1.12.8.1) and a number of hydroxylases, such as tyrosinase (62.1.12.11.2) and dopamine-jS-hydroxylase (62.1.12.11.3). Tyrosinase and hemocyanin have similar binuclear copper centres. 

Smirnov V. V. Roth J. P. Mechanisms of electron transfer in catalysis by copper zinc superoxide dismutase. J. Am. Chem. Soc. 2006, 128, 16424—16425. 

Another illustration of the power of molecular dynamics simulation can be drawn from the sphere of enzyme catalysis. Many enzyme-catalyzed reactions proceed at a rate that depends on the diffusion-limited association of the substrate with the active site. Sharp et al. [28] have carried out Brownian dynamics simulations of the association of superoxide anions with superoxide dismutase (SOD). The active center in SOD is a positively charged copper atom. The distribution of charge over the enzyme is not uniform, and so an electric field is produced. Using their model, Sharp et al. [28] have shown that the electric field enhances the association of the substrate with the enzyme by a factor of 30 or more. Their calculations also predict correctly the response of the association rate to changes in ionic strength and amino... 

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],... 

C19. Crow, J. P., Sampson, J. B., Zhuang, Y., Thompson, J. A., and Beckman, J. S., Decreased zinc affinity of amyotrophic lateral sclerosis-associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J. Neurochem. 69, 1936-1944 (1997). 

Mn catalase cycles between the Mn /Mfo and the Mn /Mn oxidation states during catalysis and is thus, in some sense, the two-electron analog of Mn superoxide dismutase. One possible mechanistic model, based on the known coordination chemistry of Mn dimers and the crystal structures of Mn catalase, is shown in Scheme 3. In this scheme, the bridging solvent molecules play a critical role in... 

Cabelli DE, Guan Y, Leveque V, Hearn AS, Tainer JA, Nick HS, Silverman DN. (1999) Role of tryptophan 161 in catalysis by hiunan manganese superoxide dismutase. Riochem 3% 11686-11692. 

Zinc usually binds to proteins via residues of cysteine and histidine. Sometimes, zinc is bound to residues of glutamate or aspartate. The zinc ion sometimes plays a catalytic role and sometimes a structural role. In the latter case, it helps maintain the three-dimensional structure or conformation of the protein. For example, carboxypeptidase A contains two atoms of zinc. One is required for catalytic activity and is boimd to cysteine and histidine. The other, which plays a structural role, is bound only to cysteine. Cytoplasmic superoxide dismutase is a dimer. It contains one atom of Cu " and one of Zn per subunit. The zinc is boimd via three residues of histidine and one residue of aspartate. It is buried deep within the enzyme and serves a structural role. The copper atom is bound via four residues of histidine. It resides close to the surface of the protein and participates in the chemistry of catalysis. 

The herbicidal effect of paraquat is attributable to the formation of superoxide anion (02 ). Superoxide anion is very toxic compound and is formed by the reaction of oxygen with paraquat radical (paraquat ). Plants, algae, and cyanobacteria have ferredoxin-NADP reductase to form NADPH for the reduction of carbon dioxide (see below). The chemolithoautotrophs also have NAD(P) (NAD and NADP) reductase to form NAD(P)H for the reduction of carbon dioxide. Paraquat [mid-point redox potential at pH 7.0 (Emj 0) = -0.43 V] radical is produced when paraquat is reduced by the catalysis of ferredoxin-NAD(P) reductase or NAD(P) reductase, which catalyzes the reduction of many compounds with of around -0.4 V. Although the aerobic organisms (and even many anaerobic organisms) have superoxide dismutase (SOD) which detoxifies superoxide anion in cooperation with catalase [ascorbate peroxidase in the case of plants (Asada, 1999)], the anion accumulates in the organisms when it is over-produced beyond the capacity of SOD. 

The catalyzed disproportionation (dismutation) of superoxide has been studied extensively, particularly in regard to its enzymatic catalysis by the superoxide dismutases (SODs). The superoxide dismutases are metalloenzymes and can have Cu-Zn, Fe, Mn, or Ni active sites. Simple inorganic species can also catalyze the reaction.28 For example, catalysis by Fe2+/Fe(III) at pH 7.2 has the rate law... 

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