Superoxide dismutase mechanisms

Quint P et al (2006) Crystal structure of nitrated human manganese superoxide dismutase mechanism of inactivation. Free Radio Biol Med 40 453-458 PDBID 2ADQ... 

Figure 18.22. Superoxide Dismutase Mechanism. The oxidized form of superoxide dismutase (Mq ) reacts with one superoxide ion to form O2 and generate the reduced form of the enzyme (M gj). The reduced form then reacts with a second superoxide and two protons to form hydrogen peroxide and regenerate the oxidized form of the enzyme.

As described in Section 15.7, enzymes are the catalysts of biological reactions. Without enzymes, most of the reactions that occur in a cell would be imperceptibly slow. Cations of transition metals play essential roles in the mechanisms of many enzyme-catalyzed reactions. Here we introduce just one representative example, superoxide dismutase. 

The hydroxyl radical plays two essentially different roles (a) as a reactant mediating the transformations of xenobiotics and (b) as a toxicant that damages DNA. They are important in a number of environments (1) in aquatic systems under irradiation, (2) in the troposphere, which is discussed later, and (3) in biological systems in the context of superoxide dismutase and the role of iron. Hydroxyl radicals in aqueous media can be generated by several mechanisms ... 

Zemlan, F., Thienhaus, O.J. and Bosmann, H.B. (1989). Superoxide dismutase activity in Alzheimer s disease possible mechanism for paired helical filament formation. Brain Res. 476, 160-162. 

Superoxide Dismutase. Again, only electron-capture is important on irradiation (78). For the Cu-Zn enzyme, Cu is converted into Cu form. In the presence of oxygen, 02 is formed in competition with Cu, and on annealing reacts to re-form Cu. Thus radiolysis has proven to be a useful method for checking the mechanism of action of this dismutase. The conclusion is that the somewhat disputed mechanism [21,22] is probably correct. 

J.M. McCord and I. Fridovich, Utility of superoxide dismutase in studying free radical reactions. II. Mechanism of the mediation of cytochrome c reduction by a variety of electron carriers. J. Biol. Chem. 245,1374-1377 (1970). 

M.E. Me Adam, E.M. Fielden, F. Favelle, F. Calabrese, D. Cocco, and G. Rotilio, The involvement of the bridging imidazolate in the catalytic mechanism of action of bovine superoxide dismutase. 

General descriptors may be related to the metabolism responses in the biofilm. Biofilm algae have several mechanisms to counterbalance the damage caused by the toxicants. Environmental stress produces oxidative damage in the cells, which can be tracked down by means of the analysis of many enzymes (superoxide dismutase, catalase, peroxidase, etc.) that function as effective quenchers of reactive oxygen species (ROS). 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

Figure 5.4 Detailed mechanism for superoxide dismutase activity. (Adapted with permission from Figure 8 of Hart, P. J. Balbimie, M. M. Ogihara, N. L. Versissian, A. M. Weiss, M. S. Valentine, J. S. Eisenberg, D. Biochemistry, 1999, 38, 2167-2178. Copyright 1999, American Chemical Society.)...

This discussion of copper-containing enzymes has focused on structure and function information for Type I blue copper proteins azurin and plastocyanin, Type III hemocyanin, and Type II superoxide dismutase s structure and mechanism of activity. Information on spectral properties for some metalloproteins and their model compounds has been included in Tables 5.2, 5.3, and 5.7. One model system for Type I copper proteins39 and one for Type II centers40 have been discussed. Many others can be found in the literature. A more complete discussion, including mechanistic detail, about hemocyanin and tyrosinase model systems has been included. Models for the blue copper oxidases laccase and ascorbate oxidases have not been discussed. Students are referred to the references listed in the reference section for discussion of some other model systems. Many more are to be found in literature searches.50... 

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