Fenton reaction, iron-catalyzed

From the point of view of the redox properties of the formed complex, Merkofer et al. [2006] have studied the Fenton reaction 18 catalyzed by different iron chelators and concluded that a Fe-complex can participate in cell redox cycling only when two conditions are fulfilled (i) the oxidized complex (ligand-M(" + 1 +) can be reduced by a physiologically relevant compound [e.g., NAD(P)H] [Pierre et al., 2002], then the 0 (Ligand M( +i)+/Ligand M +) is higher... 

Excess iron can lead to diabetes mellitus, faulty liver functions, and endocrine disturbance. Iron is a catalyst for oxidative damage leading to lipid peroxidation. The latest hypotheses link peroxidation to heart disease, cancer, and accelerated aging. Iron is involved in the Fenton Reaction, which catalyzes the formation of free radicals that cause excessive damage to cells and their components. 

Iron-stimulated free radical-mediated processes are not limited to the promotion of peroxidative reactions. For example, Pratico et al. [188] demonstrated that erythrocytes are able to modulate platelet reactivity in response to collagen via the release of free iron, which supposedly catalyzes hydroxyl radical formation by the Fenton reaction. This process resulted in an irreversible blood aggregation and could be relevant to the stimulation by iron overload of atherosclerosis and coronary artery disease. 

Thus, superoxide itself is obviously too inert to be a direct initiator of lipid peroxidation. However, it may be converted into some reactive species in superoxide-dependent oxidative processes. It has been suggested that superoxide can initiate lipid peroxidation by reducing ferric into ferrous iron, which is able to catalyze the formation of free hydroxyl radicals via the Fenton reaction. The possibility of hydroxyl-initiated lipid peroxidation was considered in earlier studies. For example, Lai and Piette [8] identified hydroxyl radicals in NADPH-dependent microsomal lipid peroxidation by EPR spectroscopy using the spin-trapping agents DMPO and phenyl-tcrt-butylnitrone. They proposed that hydroxyl radicals are generated by the Fenton reaction between ferrous ions and hydrogen peroxide formed by the dismutation of superoxide. Later on, the formation of hydroxyl radicals was shown in the oxidation of NADPH catalyzed by microsomal NADPH-cytochrome P-450 reductase [9,10]. 

As mentioned above, in contrast to classic antioxidant vitamins E and C, flavonoids are able to inhibit free radical formation as free radical scavengers and the chelators of transition metals. As far as chelators are concerned their inhibitory activity is a consequence of the formation of transition metal complexes incapable of catalyzing the formation of hydroxyl radicals by the Fenton reaction. In addition, as shown below, some of these complexes, for example, iron- and copper-rutin complexes, may acquire additional antioxidant activity. 

Conflicting data were also received for the reactions of LA and DHLA with hydroxyl radicals and superoxide. Suzuki et al. [206] found that both LA and DHLA inhibited the formation of DMPO-OH adducts formed in the Fenton reaction. However, Scott et al. [207] concluded that only LA is a powerful scavenger of hydroxyl radicals while DHLA accelerated iron-catalyzed hydroxyl radical formation and lipid peroxidation. 

In this classical Haber-Weiss cycle iron is being reduced by superoxide anion radical (02T), ascorbic acid or glutathione and subsequently decomposes hydrogen peroxide - formed by spontaneous dismutation of 02T - in the Fenton reaction to produce 0H. This iron-driven 0H formation has a stringent requirement for an available iron coordination site, a sine qua non met not only by hexaaquoiron(III) but by most iron chelates (28). Thus, Fe-EDTA, -EGTA, and -ATP retain a reactive coordination site and catalyze the Haber-Weiss cycle. Phytic acid, however, occupies all available iron coordination sites and consequently fails to support 0H generation (Figure 6). 

The superoxide anion radical and hydrogen peroxide are not particularly harmful to cells. It is the product of hydrogen peroxide decomposition, the hydroxyl radical (HO ), that is responsible for most of the cytotoxicity of oxygen radicals. The reaction can he catalyzed hy several transition metals, including copper, manganese, cohalt, and iron, of which iron is the most ahimdant in the human body (Reaction 2 also called the Fenton reaction). To avoid iron-catalyzed reactions, iron is transported and stored chiefly as Fe(III), although redox active iron can be formed in oxidative reactions, and Fe(III) can be reduced by semiquinone radicals (Reaction 3). 

The second reaction achieved notoriety as a possible source of hydroxyl radicals, but the reaction proceeds extremely slowly. Iron(III) complexes may catalyze this reaction in this case, Fe(III) would first be reduced by the superoxide, followed by oxidation by hydrogen peroxide. See also Fenton Reaction... 

Thus, antioxidant effects of nitrite in cured meats appear to be due to the formation of NO. Kanner et al. (1991) also demonstrated antioxidant effects of NO in systems where reactive hydroxyl radicals ( OH) are produced by the iron-catalyzed decomposition of hydrogen peroxide (Fenton reaction). Hydroxyl radical formation was measured as the rate of benzoate hydtoxylation to salicylic acid. Benzoate hydtoxylation catalyzed by cysteine-Fe +, ascorbate - EDTA-Fe, or Fe was significantly decreased by flushing of the reaction mixture with NO. They proposed that NO liganded to ferrous complexes reacted with H2O2 to form nitrous acid, hydroxyl ion, and ferric iron complexes, preventing generation of hydroxyl radicals. 

Hug, S.J. and Leupin, O. (2003) Iron-catalyzed oxidation of arsenic(in) by oxygen and by hydrogen peroxide pH-dependent formation of oxidants in the fenton reaction. Environmental Science and Technology, 37(12), 2734-42. 

Three types of SODs occur (1) extracellular (EC)-SOD, (2) manganese SOD found in the mitochondria, and (3) copper-zinc SOD found in the cytosol and nucleus. H202 can be converted to the highly toxic hydroxyl radical ("OH) via the iron-catalyzed Fenton reaction ... 

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