Superoxide dismutase model

Scheme 4. Schiff-base superoxide dismutase models surriving biological chelators. Upper section Dibenzoy Imethane does not readily react with 2-(2-aminoethyl)-pyridine due to a keto-enol tautomery. Therefore only poorly active and instable complexes are obtained. In contrast, 2-pyridine-aldehyde and putrescine yield a highly active and stable copper

Ceballos-Picot, I., Nicole, A., and 8inet, P. M., 1992, Cellular clones and transgenic mice overexpressing copper-zinc superoxide dismutase Models for the study of free radical metabolism and aging, in Free Radicals and Aging (I. Emerit and B. chance, eds.), pp. 89-98, Birkhauser, Basel, 8witzer-land. 

CL Eisher, J-L Chen, J Li, D Bashford, L Noodleman. Density-functional and electrostatic calculations for a model of a manganese superoxide dismutase active site in aqueous solution. J Phys Chem 100 13498-13505, 1996. 

Przyklenk, K. and Kloner, R.A. (1986). Superoxide dismutase plus catalase improve contractile function in the canine model of the stunned myocardium. Circ. Res. 58, 148-156. 

Ceballos-Picot, I., Nicole, A., Briand, P., Grimber, G., Delacourte, A., Defossez, A., Javoy-Agid, F., Lafon, M., Blouin, J.L. and Sinet, P.M. (1991). Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice animal model of gene dosage effects in Down s syndrome. Brain Res, 552, 198-214. 

Steer, M.L., Rutledge, P.L., Powers, R.E., Saluja, M. and Saluja, A.K. (1991). The role of oxygen-derived fiee radicals in two models of experimental acute pancreatitis effects of catalase, superoxide dismutase, dimethyl sulphoxide, and allopurinol. Klin. Wochenschr. 69, 1012-1017. 

Durham HD, Roy J, Dong L, Figlewicz DA. Aggregation of mutant Cu/ Zn superoxide dismutase proteins in culture model of ALS. J Neuropathol Exp Neurol 1997 56 523-530. 

Nickel is found in thiolate/sulflde environment in the [NiFe]-hydrogenases and in CODH/ACS.33 In addition, either a mononuclear Ni-thiolate site or a dinuclear cysteine-S bridged structure are assumed plausible for the new class of Ni-containing superoxide dismutases, NiSOD (A).34 [NiFe]-hydrogenase catalyzes the two-electron redox chemistry of dihydrogen. Several crystal structures of [NiFe]-hydrogenases have demonstrated that the active site of the enzyme consists of a heterodinuclear Ni—Fe unit bound to thiolate sulfurs of cysteine residues with a Ni—Fe distance below 3 A (4) 35-39 This heterodinuclear active site has been the target of extensive model studies, which are summarized in Section 6.3.4.12.5. 

Carloni et al.91 applied the DFT(PZ) calculations to investigate the electronic structure of various models of oxydized and reduced Cu, Zn superoxide dismutase. The first stage of the enzymatic reaction involves the electron transfer from Cu" ion to superoxide. The theoretical investigations provided a detailed description of the electronic structure of the molecules involved in the electron transfer process. The effect of charged groups, present in the active center, on the electron transfer process were analyzed and the Argl41 residue was shown to play a crucial role. 

The mitochondrial dysfunctionality seen in manganese neurotoxicity might be related to the accumulation of reactive oxygen species (Verity, 1999). Mitochondrial Mn superoxide dismutase (MnSOD) is found to be low or absent in tumour cells and may act as a tumour suppressor. It is induced by inflammatory cytokines like TNF, presumably to protect host cells. In a rat model, iron-rich diets were found to decrease MnSOD activity, although a recent study reported that in rat epithelial cell cultures iron supplementation increased MnSOD protein levels and activity, but did not compromise the ability of inflammatory mediators like TNF to further increase the enzyme activity (Kuratko, 1999). 

Turner, B. J., Lopes, E. C. and Cheema, S. S. Neuromuscular accumulation of mutant superoxide dismutase 1 aggregates in a transgenic mouse model of familial amyotrophic lateral sclerosis. Neurosci. Lett. 350 132-136, 2003. 

Figure 5.10 Models for superoxide dismutase as illustrated in reference 40. (A) [Cu2(bpz-biap)Cl3] (1) and (B) [Cu2(Hbzbiap)Cl4] (2).

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... 

Cu,Zn superoxide dismutase. Essentially, these observations support a stepwise one-electron model again. Interestingly, the oxidation state of copper does not change during the catalytic reaction, i.e. the sole kinetic role of the histidine coordinated metal center is to alter the electronic structures of the substrate and 02 in order to facilitate the electron transfer process between them. 

A. Type I—Direct-Stacking Models Transthyretin and Superoxide Dismutase... 

Johnston, J. A., et al.. Formation of high molecular weight complexes of mutant Cu, Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis. Proc Natl Acad Sci USA, 2000, 97(23), 12571-6. 

Corvo ML, Boerman OC, Oyen WJ, et al. Intravenous administration of superoxide dismutase entrapped in long circulating liposomes. II. In vivo fate in a rat model of adjuvant arthritis. Biochim Biophys Acta 1999 1419 325. 

Transition metal hydroperoxo species are well established as important intermediates in the oxidation of hydrocarbons (8,70,71). As they relate to the active oxygenating reagent in cytochrome P-450 monooxygenase, (porphyrin)M-OOR complexes have come under recent scmtiny because of their importance in the process of (poiphyrin)M=0 formation via 0-0 cleavage processes (72-74). In copper biochemistry, a hydroperoxo copper species has been hypothesized as an important intermediate in the catalytic reaction of the copper monooxygenase, dopamine P-hydroxylase (75,76). A Cu-OOH moiety has also been proposed to be involved in the disproportionation of superoxide mediated by the copper-zinc superoxide dismutase (77-78). Thus, model Cun-OOR complexes may be of... 

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