Peroxynitrite disease roles

A number of NO-derived reactive species can initiate lipid peroxidation, including nitrogen dioxide and, most notably, ONOO , which displays unique properties as a mediator of lipid oxidation. On a molecular basis, ONOO is a more potent lipid oxidant than hydrogen peroxide and, unlike H2O2, it does not require metal catalysis. The one-electron oxidants such as metals, as well as heme proteins and peroxynitrite, are assumed to play an important role in many diseases associated with oxidative stress. Heme proteins such as horseradish peroxidase (HRP) can produce alkylperoxyl radicals through two sequential... 

Ebadi, M., Sharma, S., Ghafourifar, P., Brown-Borg, H., and El Refaey, H., Peroxynitrite in the pathogenesis of Parkinson s disease and the neuroprotective role of metallothionein, Methods Enzymol., 396, 276-298, 2005. 

The xanthine oxidoreductases are large, complex molybdo-flavoproteins with roles in the catabolism of purines, for example, oxidizing hypoxanthine to xanthine and xanthine to uric acid (equation 9). Xanthine oxidase can also catalyze the reduction of nitrate to nitrite (or in the presence superoxide, peroxynitrite) and the reduction of nitrite to nitric oxide. Peroxynitrite, a powerfiil and destructive oxidant, has been implicated in diseases such as arthritis, atherosclerosis, multiple sclerosis, and Alzheimer s and Parkinson s diseases. The microbicidal role of milk and intestinal xanthine oxidase may also involve the generation of peroxynitrite in the gut. The high levels of the enzyme in the mammary glands of pregnant... 

Enhanced production of vasoconstrictor factors via eicosanoid and/or free radical-related mechanisms has been observed in several cardiovascular disease states. In addition to the well-established role of free radicals in promoting the oxidation of low density lipoprotein cholesterol (LDL-C), changes in free radical status may modify endogenous eicosanoid profiles and/or produce nonenzymatic lipid peroxidation products of the arachidonic acid (AA) cascade such as lipid hydroperoxides and isoprostanes, which have been shown to possess potent vasoactive properties (3). Furthermore, an excess of free radicals may interact with the vascular endothelial cell nitric oxide (NO) to produce highly reactive peroxynitrite radicals, resulting in tissue damage and vasoconstriction (4—6) (Fig. 2). 

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