期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1840, 期 2, 页码 768-780出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2013.07.005
关键词
Free radical; Nitrotyrosine; Peroxynitrite; Oxidative stress; Superoxide radical; Nitric oxide
资金
- Universidad de la Republica, Programa de Desarrollo Ciencias Basicas (PEDECIBA)
- Agencia Nacional de Investigacion e Innovacion (ANII)
- National Institutes of Health [RO1AI095173]
- Comision Sectorial de Investigacion Cientifica (CSIC, Universidad de la Republica)
- ANII (Fondo Clemente Estable) [FCE_2486, FCE_6605]
Background: Peroxynitrite, the product of the reaction between superoxide radicals and nitric oxide, is an elusive oxidant with a short half-life and a low steady-state concentration in biological systems; it promotes nitroxidative damage. Scope of review: We will consider kinetic and mechanistic aspects that allow rationalizing the biological fate of peroxynitrite from data obtained by a combination of methods that include fast kinetic techniques, electron paramagnetic resonance and kinetic simulations. In addition, we provide a quantitative analysis of peroxynitrite production rates and conceivable steady-state levels in living systems. Major conclusions: The preferential reactions of peroxynitrite in vivo include those with carbon dioxide, thiols and metalloproteins; its homolysis represents only <1% of its fate. To note, carbon dioxide accounts for a significant fraction of peroxynitrite consumption leading to the formation of strong one-electron oxidants, carbonate radicals and nitrogen dioxide. On the other hand, peroxynitrite is rapidly reduced by peroxiredoxins, which represent efficient thiol-based peroxynitrite detoxification systems. Glutathione, present at mM concentration in cells and frequently considered a direct scavenger of peroxynitrite, does not react sufficiently fast with it in vivo; glutathione mainly inhibits peroxynitrite-dependent processes by reactions with secondary radicals. The detection of protein 3-nitrotyrosine, a molecular footprint, can demonstrate peroxynitrite formation in vivo. Basal peroxynitrite formation rates in cells can be estimated in the order of 0.1 to 0.5 mu M s(-1) and its steady-state concentration at similar to 1 nM. General significance: The analysis provides a handle to predict the preferential fate and steady-state levels of peroxynitrite in living systems. This is useful to understand pathophysiological aspects and pharmacological prospects connected to peroxynitrite. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. (C) 2013 Elsevier B.V. All rights reserved.
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