Peroxynitrite carbon dioxide

The reaction of peroxynitrite with the biologically ubiquitous C02 is of special interest due to the presence of both compounds in living organisms therefore, we may be confident that this process takes place under in vivo conditions. After the discovery of this reaction in 1995 by Lymar [136], the interaction of peroxynitrite with carbon dioxide and the reactions of the formed adduct nitrosoperoxocarboxylate ONOOCOO has been thoroughly studied. In 1996, Lymar et al. [137] have shown that this adduct is more reactive than peroxynitrite in the reaction with tyrosine, forming similar to peroxynitrite dityrosine and 3-nitrotyrosine. Experimental data were in quantitative agreement with free radical-mediated mechanism yielding tyrosyl and nitric dioxide radicals as intermediates and were inconsistent with electrophilic mechanism. The lifetime of ONOOCOO was estimated as <3 ms, and the rate constant of Reaction (42) k42 = 2 x 103 1 mol 1 s 1. 

Heterolytic mechanism is important in the absence of substrates and homolytic one occurs in the presence of oxidizable biomolecules. Bonini et al. [139] were able to identify C03 radical in the reaction of peroxynitrite with carbon dioxide by ESR spectroscopy. 

Analytical methods for ONOO related to the vascular system have been reviewed. Special attention is given to assays involving oxidation of dihydrorhodamine 123 (345) to yield the fluorescent product rhodamine 123 (346, equation 118), luminol (124) CL and nitrotyrosine formation. The reaction of peroxynitrite and carbon dioxide or bicarbonate... 

Guanine is the most easily oxidizable natural nucleic acid base [8] and many oxidants can selectively oxidize guanine in DNA [95]. Here, we focus on the site-selective oxidation of guanine by the carbonate radical anion, COs , one of the important emerging free radicals in biological systems [96]. The mechanism of COs generation in vivo can involve one-electron oxidation of HCOs at the active site of copper-zinc superoxide dismutase [97, 98], and homolysis of the nitrosoperoxycarbonate anion (0N00C02 ) formed by the reaction of peroxynitrite with carbon dioxide [99-102]. 

The fates of the G(-H) radicals in DNA are mostly determined by reactions with other substrates. Here, we consider the reactions of the G(-H) radicals with types of free radicals that are generated in vivo under conditions of oxidative stress. One of these radicals is the nitrogen dioxide radical, NO2. This radical can be generated in vivo by the oxidation of nitrite, N02, a process that can be mediated by myeloperoxidase [111, 112] as well as by other cellular oxidants [113, 114]. An alternative pathway of the generation of NO2 is the homolysis of peroxynitrite [102, 115] or nitrosoperoxycarbonate formed by the reaction of peroxynitrite with carbon dioxide [99-101]. The redox potential, E°( NO2/NO2")=1.04 V vs NHE [116] is less than that of guanine, E7[G(-H)7G] = 1.29 V vs NHE [8]. Pulse radiolysis [117] and laser flash photolysis [109] experiments have shown that, in agreement with these redox potentials, N02 radicals do not react with intact DNA. However, N02 radicals can oxidize 8-oxo-dG that has a lower redox potential ( 7=0.74 vs NHE [56]) than any of the normal nucleobases [109]. 

In vivo, peroxynitrite may be intercepted by various cellular agents which will keep its steady-state low (Table 2.4). Not all these interceptors, however, react with peroxynitrite to non-reactive products. For example, carbon dioxide enhances tyrosine nitration and thiyl radical formation. Myeloperoxidase also enhances tyrosine nitration, and in the reactions with GSH and albumin thiyl radicals are formed (for details see Arteel et al. 1999). 

Denicola A, Freeman BA, Trujillo M, Radi R (1996) Peroxynitrite reaction with carbon dioxide/bicar-bonate kinetics and influence on peroxynitrite-mediated oxidations. Arch Biochem Biophys 333 49-58... 

Lymar SV, Jiang Q, Hurst JK (1999) Mechanism of carbon dioxide-catalyzed oxidation of tyrosine by peroxynitrite. Biochemistry 35 7855-7861... 

Yermilov V, Rubio J, Ohshima H (1995) Formation of 8-nitroguanine in DNA treated with peroxyni-trite in vitro and its rapid removal from DNA by depurination. FEBS Lett 376 207-210 Yermilov V, Yoshie Y, Rubio J, Oshima H (1996) Effects of carbon dioxide/bicarbonate on induction of DNA single-strand breaks and formation of 8-nitroguanine, 8-oxoguanine and base-propenal mediated by peroxynitrite. FEBS Lett 399 67-70... 

Zhang H, SquadritoGL, Uppu RM, Lemercier J-N,Cueto R, Pryor WA (1997) Inhibition of peroxynitrite-mediated oxidation of glutathione by carbon dioxide. Arch Biochem Biophys 339 183-189... 

Lu JM, Geimer J, Naumov S, Beckert D (2001) A Fourier transform EPR study of uracil and thymine radical anions in aqueous solution. Phys Chem Chem Phys 3 952-956 Lymar SV, Jiang Q, Hurst JK (1999) Mechanism of carbon dioxide-catalyzed oxidation of tyrosine by peroxynitrite. Biochemistry 35 7855-7861... 

G.L. Squadrito et al., Oxidative chemistry of nitric oxide The roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic. Biol. Med. 25, 392-403 (1998)... 

R.M. Uppu et al., Acceleration of peroxynitrite oxidations by carbon dioxide. Arch. Biochem. Biophys. 327, 335-343 (1996)... 

M.G. Bonini et al., Direct EPR detection of the carbonate radical anion produced from peroxynitrite and carbon dioxide. J. Biol. Chem. 274, 10802-10806 (1999)... 

M.C. Gonzalez et al., QM-MM investigation of the reaction of peroxynitrite with carbon dioxide in water. J. Chem. Theory Comput. 3, 1405-1411 (2007)... 

Despite the presence of a large concentration of carbon dioxide in the blood (ca. 1 him), it has been reported that peroxynitrite can diffuse across the red-blood-cell membrane and react with oxyHb [24]. The anionic form (ONOO-) crosses the erythrocyte membrane by using the anion channel band 3 whereas peroxynitrous acid crosses the lipid membranes by rapid passive diffusion [24]. 

Differently from HNO3, HOONO is a weak add (see reaction 10). The anion, peroxynitrite, was shown to react with carbon dioxide to yield the nitrating agent 0N00C02 [73,74]. In contrast, peroxynitrous acid is too short-lived to undergo such a reaction [75]. 

L28. Lymar, S. V., and Hurst, J. K., Carbon dioxide physiological catalyst for peroxynitrite-mediated cellular damage or cellular protectant Chem. Res. Toxicol. 9, 845-850 (1996). 

V3. Vasquez-Vivar, J., Denicola, A., Radi, R., and Augusto, O., Peroxynitrite-mediated decarboxylation of pyruvate to both carbon dioxide and carbon dioxide radical anion. Chem. Res. Toxicol. 10, 786-794 (1997). 

Fig. 3 Formation of peroxynitrite from nitric oxide and superoxide anion and reaction products with carbon dioxide...

In the presence of physiological levels of carbon dioxide in the cells, peroxynitrite is converted to nitrosoperoxocarboxylate adduct (ONOOCOj), which decays with a rate constant of 4.6 x 10 s ... 

G. L. Squadrito, W. A. Pryor, Oxidative Chemistry of Nitric Oxide The Roles of Superoxide. Peroxynitrite, and Carbon Dioxide, Free Radic Biol Med 15 (1998) 392-403. 

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