Hydroxyl radical formation from peroxynitrite

Beckman, J.S., Beckman, T.W., Chen, J., Marshall, P.A. and Freeman, B.A. (1990). Apparent hydroxyl radical formation by peroxynitrite implications for endothelial cell injury from nitric oxide and superoxide anion. Proc. Natl Acad. Sci. USA 87, 1620-1624. 

This conclusion is partly true because superoxide is unable to abstract hydrogen atom even from the most active bisallylic positions of unsaturated compounds, while perhydroxyl radical abstracts H atom from linoleic, linolenic, and arachidonic fatty acids with the rate constants of 1-3 x 1031 mol-1 s-1 [24], However, the superoxide damaging activity does not originate from hydrogen atom abstraction reactions but from one-electron reduction processes, leading to the formation of hydroxyl radicals, peroxynitrite, etc, and in these reactions perhydroxyl cannot compete with superoxide. 

Fig. 3. Production of reactive species. (A) ROS can be produced from the weak radical oxygen in the mitochondria and endoplasmic reticulum, by various enzymatic reactions, and from oxyhemoglobin. Normally, nontoxic hydrogen peroxide can give rise to the powerful hydroxyl radical in the presence of transition metals (R5). Oxygen can also be induced to react with biomolecules by transition metals and enzymes. RNS can be produced by reaction of superoxide anion radical with the weak radical nitric oxide. These can react to form the powerful oxidant peroxynitrite/peroxynitrous acid, which can cause formation of other radicals, some with longer lives. See the text for details. SOD, superoxide dismutase. (B) Myeloperoxidase in leukocytes can produce the reactive species hypochlorous acid and tyrosyl radical. Unpaired electrons are indicated by the dense dots and paired electrons by the light ones.

Now, we will consider the major reactions of peroxynitrite with biomolecules. It was found that peroxynitrite reacts with many biomolecules belonging to various chemical classes, with the bimolecular rate constants from 10-3 to 10s 1 mol 1 s 1 (Table 21.2). Reactions of peroxynitrite with phenols were studied most thoroughly due to the important role of peroxynitrite in the in vivo nitration and oxidation of free tyrosine and tyrosine residues in proteins. In 1992, Beckman et al. [112] have showed that peroxynitrite efficiently nitrates 4-hydroxyphenylacetate at pH 7.5. van der Vliet et al. [113] found that the reactions of peroxynitrite with tyrosine and phenylalanine resulted in the formation of both hydroxylated and nitrated products. In authors opinion the formation of these products was mediated by N02 and HO radicals. Studying peroxynitrite reactions with phenol, tyrosine, and salicylate, Ramezanian et al. [114] showed that these reactions are of first-order in peroxynitrite and zero-order in phenolic compounds. These authors supposed that there should be two different intermediates responsible for the nitration and hydroxylation of phenols but rejected the most probable proposal that these intermediates should be NO2 and HO. ... 

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