Superoxide reactive species

Normally, these reactive species are destroyed by protective enzymes, such as superoxide dismutase in mitochondria and cytosol and catalase in peroxisomes, but if a tissue has been anoxic the respiratory chain is very reduced and reoxygenation allows dangerous amounts to be formed. Muscle also contains significant quantities of the dipeptide, camosine ((J-alanylhistidine) (10—25 mM). The functions of camosine are obscure although it has been suggested to be an effective antioxidant (Pavlov et al., 1993). 

Peroxynitrite (ONOO-) is a cytotoxic reactive species that is formed by the reaction of nitric oxide and superoxide. Methods for measuring the scavenging capacity of peroxynitrite usually depend on either the inhibition of tyrosine nitration or the inhibition of dihydrorhodamine 123 (DHR) oxidation to rhodamine 123 (MacDonalds-Wicks and... 

This mode of superoxide-dependent free radical-mediated damaging activity remains an important one although the nature of the generated reactive species (free hydroxyl radicals or perferryl, or ferryl ions) is still obscure. However, after the discovery of the fact that many cells produce nitric oxide in relatively large amounts (see below), it became clear that there is another and possibly a more portent mechanism of superoxide-induced free radical damage, namely, the formation of highly reactive peroxynitrite. 

Reaction of nitric oxide with superoxide is undoubtedly the most important reaction of nitric oxide, resulting in the formation of peroxynitrite, one of the main reactive species in free radical-mediated damaging processes. This reaction is a diffusion-controlled one, with the rate constant (which has been measured by many workers, see, for example, Ref. [41]), of about 2 x 109 1 mol-1 s-1. Goldstein and Czapski [41] also measured the rate constant for Reaction (11) ... 

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]. 

Later on, other hydroxylamine derivatives such as 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine (TEMPONEH) and l-hydroxy-3-carboxy-pyrrolidine (CP-3) have been used for superoxide detection [26]. It was found that these spin traps react with both superoxide and peroxynitrite and that they might be applied for quantification of these reactive species [27]. The CP-3 radical is less predisposed to reduction by ascorbic acid and therefore is probably more suitable for superoxide detection in biological systems. 

Possel et al. [104] also concluded that DCFH is more sensitive to peroxynitrite oxidation than DHR. Unfortunately, both compounds are oxidized by other reactive species (for example, DCFH by superoxide and DHR by HOC1), and therefore, their use for peroxynitrite detection must be confirmed by the other methods. 

Reactions of 02 with Alkanes and Alkenes. When compared with 0, the superoxide ion is a much less reactive species. Since the 02 is thermally stable up to -175°C, stoichiometric reactions must be carried out at 175°C or lower temperatures (12). Methane is essentially unreactive with 02 at 175°C, and the reaction with ethylene and propane is slow. Essentially all of the 02 ions re-... 

An extremely interesting feature of these mechanisms is the fact that superoxide and the alkene radical cation are both formed in the reduction (Fig. 20) and also in the Frei oxidation (Fig. 19). In the Frei photo-oxidation, however, they are formed concurrently in a tight ion pair and collapse to product more rapidly than their diffusive separation. In the reduction (Fig. 20), the formation of the radical cation and superoxide occur in independent spatially separated events allowing the unimpeded diffusion of superoxide which precludes back-electron transfer (BET) and formation of oxidized products. The nongeminate formation of these two reactive species provides the time necessary for the radical cation to abstract a hydrogen atom from the solvent on its way to the reduced product. 

Hydroxide radical or HO. The hydroxide radical is an extremely reactive species that can damage cells. It can be generated by activated macrophages via superoxide and nitric oxide (especially peroxynitrite). 

A photooxidative reaction in which molecular oxygen is incorporated into the reaction products(s). Three mechanisms appear to be common for such processes (a) reaction of triplet O2 with free radicals that have been generated photochemically (b) reaction of photochemically produced singlet oxygen with a molecular species and (c) the production of superoxide anion which then acts as the reactive species. See also Photooxidation... 

Oxygen-utilizing organisms have generally evolved specific enzyme-mediated systems that serve to protect the cell from such reactive species. These enzymes include superoxide dismutase (SOD) and catalase or glutathione peroxidase (GSH-px), which catalyse the following reactions ... 

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