Metals and oxidative stress

Displacing the Essential Metal Ion in Biomolecules. It is estimated that approximately one third of all enzymes require metal as a cofactor or as a structural component. Those that involve metals as a structural component do so either for catalytic capability, for redox potential, or to confer steric arrangements necessary to protein function. Metals can cause toxicity via substitution reactions in which the native, essential metal is displaced/replaced by another metal. In some cases, the enzyme can still function after such a displacement reaction. More often, however, enzyme function is diminished or completely abolished. For example, Cd can substitute for Zn in the protein famesyl protein transferase, an important enzyme in adding famesyl groups to proteins such as Ras. In this case, Cd diminishes the activity of the protein by 50%. Pb can substitute for Zn in 8-aminolevulinic acid dehydratase (ALAD), and it causes inhibition in vivo and in vitro. ALAD contains eight subunits, each of which requires Zn. Another classic example of metal ions substituting for other metal ions is Pb substitution for Ca in bones. 

Modifying the Active Conformation of Biomolecules. Class B metals such as Hg have been shown to alter the steric conformation of proteins via interactions with sulfur atoms, particularly disulphide bonds. For example, Hg insertion between the two sulfurs involved in a disulfide bond can significantly alter the shape of the protein and reduce or abolish its activity. This has been demonstrated with ribonuclease, for example. 

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W15. Wolff, S. P., Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications. Br. Med. Bull. 49, 642-652 (1993). 

Dalton TP, Paria BC, Fernando LP, Huet-Hudson YM, Dey SK and Andrews GK (1997) Activation of the chicken metallothionein promoter by metals and oxidative stress in cultured cells and transgenic mice. Comp Biochem Physiol B Biochem Mol Biol 116 75 -86. 

The surface-phase layers will difier in character depending on the stractures of metal and oxide. On certain metals (zinc, cadmium, magnesium, etc.), loose, highly porous layers are formed which can attain appreciable thicknesses. On other metals (aluminum, bismuth, titanium, etc.), compact layers with low or zero porosity are formed which are no thicker than 1 pm. In a number of cases (e.g., on iron), compact films are formed wfiicfi fiave a distorted lattice, owing to the influence of substrate metal stracture and of the effect of chemical surface forces. The physicochemical and thermodynamic parameters of such films differ from tfiose of ordinary bulk oxides. Because of the internal stresses in the distorted lattice, such films are stable only when their thickness is insignificant (e.g., up to 3 to 5 nm). 

REDOX METAL IONS, OXIDATIVE STRESS AND NEURODEGENERATIVE DISEASES... 

Schutzendubel, A., and Polle, A., 2002, Plant responses to abiotic stresses heavy metal-induced oxidative stress and protection by mycorrhization, J. Exp. Bot. 53 1351-1365. 

Reactive oxygen species production is largely catalyzed by transition metals (especially copper and iron), and oxidative stress plays a critical role in AD pathogenesis. In one study, the association of metal levels and Ap toxicity was demonstrated by (i) the effect on cell viability by metal alone and in the combination with APP and Ap, (ii) Ap-induced neurotoxicity relevant to oxidative stress indicated by ROS production, and (iii) APPsw cells expressed APP and generated Ap, so that Ap Cu2+ and APP Cu2+ can catalyze more ROS generation than APP cells that only expressed APP. 

Mehta, A., Flora, S.J.S. (2001). Possible role of metal redistribution, hepatotoxicity and oxidative stress in chelating agents induced hepatic and renal metallothionein in rats. Food. Chem. Toxicol. 39 1029-38. 

Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005 12(10) 1161-208. 

Phillips et al. [27] studied the surface chemistry of IL-lubricated steel/steel sliding contacts under temperature variation from room temperature to 300 C. This study was focused on understanding the high-temperature stability of the liquids in contact with metal under tribological stress [27]. Some Fe samples were oxidized to Fe Oj and FOjO via thermal evaporation prior to treatment with ILs. The metallic and oxidized Fe samples were then reacted with ILs at elevated temperatures. Results showed that the friction coefficient of different fluorinated ILs was below... 

Oxidative stress can be caused by a wide variety of factors, including inflammatory responses to infections or immune activation, exposure to heavy metals or toxic substances (Carpenter et al., 2002), and oxidative stress increases during the natural course of aging (Junqueira et al., 2007). When oxidative stress is induced by environmental exposures it represents a significant component of the toxicity syndrome, and most xenobiotics share the ability to cause oxidative stress. As a consequence, the effects of multiple exposures are additive at the level of oxidative stress. Metabolic changes associated with oxidative stress can be considered to be adaptive responses that increase prospects for survival during these stressful episodes. 

O2)" biochemistry is strongly influenced by transition metals. Tyler (1975) reasoned that lipid peroxidation (LPO) in membranes occurs only in the presence of iron (for iron and oxidative stress see Section 4.1.4). 

P. Kovacic, WJ. Popp, J.R. Ames and M.D. Ryan, Anti-cancer action of metal complexes electron transfer and oxidative stress Anti-Cancer Drug Des., 3 (1988) 205. 

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