Nitration by peroxynitrite

Similar to peroxynitrite, ONOOCOO- reacts with many biomolecules such as uric acid [110], oxyhemoglobin [133], melatonin [135], NADH, ubiquinol Q0, and glutathione [141], Reactions of ONOOCOO with substrates in mitochondrial matrix is accompanied by protein nitration [141]. The reaction of ONOOCOO- with GSH was so rapid that glutathione inhibited tyrosine nitration by peroxynitrite in the presence of C02 [142], The formation of ONOOCOO- increased the formation of 3-nitrotyrosine and decreased the formation of 3-hydroxytyrosine probably due to the enhanced selectivity of C03 - compared to hydroxyl radicals [143],... 

The formation of peroxynitrite in cells and tissue is frequently characterized by the formation of nitrotyrosine. The formation of nitrotyrosine is not a very specific assay of peroxynitrite detection because the other nitrogen oxide may also take part in this process, but peroxynitrite is undoubtedly the most efficient nitrating agent. (Mechanism of tyrosine nitration by peroxynitrite and other reactive nitrogen compounds has been considered in Chapters 21 and 22.)... 

Deleterious protein cross-linking can also be induced by reactive nitrogen species (RNS) such as peroxynitrite ONOO formed by the reaction of superoxide with nitric oxide (NO). The cross-links are formed between tyrosine residues following nitration by peroxynitrite (Sitte, 2003). Carnosine appears to play roles not only in NO generation but also in protection against excess NO production by inducible nitric oxide synthetase (NOS), thereby preventing ONOO-mediated protein modification (Fontana et ah, 2002). Evidence for a carnosine-NO adduct has also been published (Nicoletti et al., 2007). 

Metal-catalyzed nitration by peroxynitrite also provides an alternative explanation to the Haber-Weiss reaction for the role of transition metals in oxidative tissue injury. The rate of peroxynitrite reaction with Fe " EDTA is 5700 M , which is in the same range as the rate of hydrogen peroxide reacting with... 

C19. Crow, J. P., Sampson, J. B., Zhuang, Y., Thompson, J. A., and Beckman, J. S., Decreased zinc affinity of amyotrophic lateral sclerosis-associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J. Neurochem. 69, 1936-1944 (1997). 

T. Sawa, T. Akaike, H. Maeda, Tyrosine Nitration by Peroxynitrite Formed from Nitric Oxide and Superoxide Generated by Xanthine Oxidase, J Biol Chem (2000). 

It was shown that tryptophan is also nitrated by peroxynitrite in the absence of transition metals to one predominant isomer of nitrotryptophan, as determined from spectral characteristics and liquid chromatography-mass spectrometry analysis. Typical hydroxyl radical scavengers partially inhibited the nitration" . The yields of the nitration of tyrosine and salicylate by peroxynitrite are significantly improved by the Fe(III)-EDTA complex " ". ... 

Pannala A, Razaq R, Halliwell B, Singh S and Rice-Evans CA. 1998. Inhibition of peroxynitrite dependent tyrosine nitration by hydroxycinnamates nitration or electron donation Free Radic Biol Med 24(4) 594-606. 

Peroxynitrite (ONOO ) is a cytoxic species that is considered to form nitric oxide (NO) and superoxide (Oj ) in biological systems (Beckman et al. 1990). The toxicity of this compound is attributed to its ability to oxidize, nitrate, and hydroxylate biomolecules. Tyrosine is nitrated to form 3-nitrotyrosine (Ramazanian et al. 1996). Phenylalanine is hydroxylated to yield o-, m-, and p-tyrosines. Cysteine is oxidized to give cystine (Radi et al. 1991a). Glutathione is converted to S-nitro- or S-nitroso derivatives (Balazy et al. 1998). Catecholamines are oxidatively polymerized to melanin (Daveu et al. 1997). Lipids are also oxidized (Radi 1991b) and DNA can be scissored by peroxynitrite (Szabo and Ohshima 1997). 

The decay of LMOONO, generated either as in Eq. (36), or by substitution of peroxynitrite into a metal complex, is usually written as a homolytic process of Scheme 9. The LMO and N02 so generated can then either diffuse apart or recombine within the solvent cage to either regenerate the peroxynitrito complex or form the metal-nitrato intermediate, followed by release of free nitrate by hydrolysis. At the time we initiated the work described below, there were no clear examples of LMOONO species isomerizing to a metal nitrato complex, although such reactions have been considered as a possibility (180-182). 

Beckman J. S., Ischiropoulos H., Zhu L., van der Woerd M., Smith C., Chen J., Harrison J., Martin J. C., and Tsai M. (1992). Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. Arch. Biochem. Biophys. 298 438 145. 

V2. van der Vliet, A., O Neill, C. A., Halliwell, B., Cross, C. E., and Kaur, H., Aromatic hydroxylation and nitration of phenylalanine and tyrosine by peroxynitrite. Evidence for hydroxyl radical production from peroxynitrite. FEBS Lett. 339, 89—92 (1994). 

Yl. Yamakura, F., Taka, H., Fujimura, T., and Murayama, K., Inactivation of human manganese-superoxide dismutase by peroxynitrite is caused by exclusive nitration of tyrosine 34 to 3-nitrotyrosine. J. Biol. Chem. 273, 14085-14089 (1998). 

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