Superoxide formation from

SOF Inhibition of W-formylmethionyl-leucyl-phenylalanine (FMLP) induced superoxide formation from rat neutrophils [122]... 

J. Vasquez-Vivar, N. Hogg, K.A. Pritchard, and B. Kalyanaraman, Superoxide anion formation from ludgenin an electron spin resonance spin-trapping study. FEBS Lett. 403, 127—130 (1997). 

Now, we may consider in detail the mechanism of oxygen radical production by mitochondria. There are definite thermodynamic conditions, which regulate one-electron transfer from the electron carriers of mitochondrial respiratory chain to dioxygen these components must have the one-electron reduction potentials more negative than that of dioxygen Eq( 02 /02]) = —0.16 V. As the reduction potentials of components of respiratory chain are changed from 0.320 to +0.380 V, it is obvious that various sources of superoxide production may exist in mitochondria. As already noted earlier, the two main sources of superoxide are present in Complexes I and III of the respiratory chain in both of them, the role of ubiquinone seems to be dominant. Although superoxide may be formed by the one-electron oxidation of ubisemiquinone radical anion (Reaction (1)) [10,22] or even neutral semiquinone radical [9], the efficiency of these ways of superoxide formation in mitochondria is doubtful. 

Spin trapping has been widely used for superoxide detection in various in vitro systems [16] this method was applied for the study of microsomal reduction of nitro compounds [17], microsomal lipid peroxidation [18], xanthine-xanthine oxidase system [19], etc. As DMPO-OOH adduct quickly decomposes yielding DMPO-OH, the latter is frequently used for the measurement of superoxide formation. (Discrimination between spin trapping of superoxide and hydroxyl radicals by DMPO can be performed by the application of hydroxyl radical scavengers, see below.) For example, Mansbach et al. [20] showed that the incubation of cultured enterocytes with menadione or nitrazepam in the presence of DMPO resulted in the formation of DMPO OH signal, which supposedly originated from the reduction of DMPO OOH adduct by glutathione peroxidase. 

Gardner and Fridovich [85] proposed that the inactivation of aconitase might be used as an assay of superoxide formation in cells. The mechanism of the interaction of superoxide with aconitases has been considered in Chapter 21. As follows from data presented in that chapter, peroxynitrite is also able to inactivate aconitases rapidly therefore, this method cannot be a specific assay of superoxide detection. 

These pathways are thought to result in the production of superoxide (13) or in the release of superoxide directly from the particles themselves. Superoxide production leads to the formation of hydrogen peroxide, and metal ions such as Fe + react with hydrogen peroxide to produce the hydroxyl radical. It is well documented that the hydroxyl radical can damage DNA as well as lipids and proteins (18, 19). Some of the health effects of cigarette tar and smoke are attributed to free radicals that can initiate production of superoxide and hydroxyl radical (3, 10, 11, 20, 21). (Adapted from Dellinger et al., 2001)... 

Similarly, catechin polymers formed upon horseradish peroxidase-catalyzed oxidation of catechin or polycondensation of catechin with aldehydes prove much more efficient than catechin (at identical monomer concentration) at inhibiting XO and superoxide formation. A more detailed investigation with the catechin-acetaldehyde polycondensate (which is expected to form in wine because of the microbial oxidation of ethanol to acetaldehyde) shows that inhibition is noncompetitive to xanthine and likely occurs via binding to the FAD or Fe/S redox centers involved in electron transfers from the reduced molybdenum center to dioxygen with simultaneous production of superoxide. 

The effect of the concentration of base requires that the formation of superoxide from peroxide is more rapid and occurs to a greater extent at the higher base concentrations. This conclusion is difficult to test, because both potassium peroxide and potassium superoxide are insoluble in the oxidation solvent and potassium superoxide precipitates from solution with as much as 35% by weight of potassium terf-butoxide or potassium hydroxide (which can be removed by extraction with tert-butyl... 

Ischiropoulos, H., Zhu, L., and Beckman, J. S. (1992a). Peroxynitrite formation from activated rat alveolar macrophages. Arch. Biochem. Biophys. 298, 446-451. Ischiropoulos, H., Zhu, L., Chen, J., Tsai, H. M., Martin, J. C., Smith, C. D., and Beckman, J. S. (1992b). Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch. Biochem. Biophys. 298, 431-437. 

Xanthine oxidase catalyzes the formation of urate and superoxide anion from xanthine. Quercetin and baicalein inhibit both xanthine oxidase and xanthine dehydrogenase. The level of xanthine oxidase is high in patients with hepatitis and brain tumor and select flavonoids might be useful in treating this disorder. 

Bowman PD, Betz AL, Goldstein GW (1982) Primary culture of microvascular endothelial cells from bovine retina selective growth using fibronectin coated substrate and plasma derived serum. In Vitro 18 626-632 Chat M, Bayol-Denizot C, Suleman G et al. (1998) Drug metabolizing enzyme activities and superoxide formation in primary and immortalized rat brain endothelial cells. Life Sci 62 151-163... 

Epidemiological studies suggest that niacin may be implicated in the pathogenesis of Parkinson s disease via the following process. NAD produced from niacin releases nicotinamide via poly(ADP-ribosyl)ation which is activated in Parkinson s disease. Released excess nicotinamide is methylated to 1-methylnicotinamide (MNA) in the cytoplasm by nicotinamide N-methyltransferase. MNA destroys several subunits of complex I via superoxide formation. This can destroy complex I subunits either directly or indirectly via mitochondrial DNA damage, and stimulates poly(ADP-ribosyl)ation. It has been proposed that this implicates nicotinamide as a potential causal agent in the development of Parkinson s disease (Fukushima et al., 2004). 

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