17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Fundamentals on the biochemistry of peroxynitrite and protein tyrosine nitration

      review-article
      a , b , * , a , b , *
      Redox Biology
      Elsevier
      Free radicals, Oxidants, Nitric oxide, Peroxynitrite and tyrosine nitration

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In this review we provide an analysis of the biochemistry of peroxynitrite and tyrosine nitration. Peroxynitrite is the product of the diffusion-controlled reaction between superoxide (O 2 -) and nitric oxide ( NO). This process is in competition with the enzymatic dismutation of O 2 •- and the diffusion of NO across cells and tissues and its reaction with molecular targets ( e.g. guanylate cyclase). Understanding the kinetics and compartmentalization of the O 2 •- / NO interplay is critical to rationalize the shift of NO from a physiological mediator to a cytotoxic intermediate. Once formed, peroxynitrite (ONOO - and ONOOH; pKa = 6,8) behaves as a strong one and two-electron oxidant towards a series of biomolecules including transition metal centers and thiols. In addition, peroxynitrite anion can secondarily evolve to secondary radicals either via its fast reaction with CO 2 or through proton-catalyzed homolysis. Thus, peroxynitrite can participate in direct (bimolecular) and indirect (through secondary radical intermediates) oxidation reactions; through these processes peroxynitrite can participate as cytotoxic effector molecule against invading pathogens and/or as an endogenous pathogenic mediator. Peroxynitrite can cause protein tyrosine nitration in vitro and in vivo. Indeed, tyrosine nitration is a hallmark of the reactions of NO-derived oxidants in cells and tissues and serves as a biomarker of oxidative damage. Protein tyrosine nitration can mediate changes in protein structure and function that affect cell homeostasis. Tyrosine nitration in biological systems is a free radical process that can be promoted either by peroxynitrite-derived radicals or by other related NO-dependent oxidative processes. Recently, mechanisms responsible of tyrosine nitration in hydrophobic biostructures such as membranes and lipoproteins have been assessed and involve the parallel occurrence and connection with lipid peroxidation. Experimental strategies to reveal the proximal oxidizing mechanism during tyrosine nitration in given pathophysiologically-relevant conditions include mapping and identification of the tyrosine nitration sites in specific proteins.

          Graphical abstract

          Highlights

          • Peroxynitrite is a reactive peroxide formed from superoxide and nitric oxide radicals.

          • Peroxynitrite is a strong one- and two-electron oxidant.

          • Protein tyrosine nitration requires free radical reactions.

          • 3-Nitrotyrosine is a biomarker of nitroxidative stress.

          • Nitration of key protein tyrosines leads to changes in protein function.

          Related collections

          Most cited references82

          • Record: found
          • Abstract: found
          • Article: not found

          Peroxynitrite: biochemistry, pathophysiology and development of therapeutics.

          Peroxynitrite--the product of the diffusion-controlled reaction of nitric oxide with superoxide radical--is a short-lived oxidant species that is a potent inducer of cell death. Conditions in which the reaction products of peroxynitrite have been detected and in which pharmacological inhibition of its formation or its decomposition have been shown to be of benefit include vascular diseases, ischaemia-reperfusion injury, circulatory shock, inflammation, pain and neurodegeneration. In this Review, we first discuss the biochemistry and pathophysiology of peroxynitrite and then focus on pharmacological strategies to attenuate the toxic effects of peroxynitrite. These include its catalytic reduction to nitrite and its isomerization to nitrate by metalloporphyrins, which have led to potential candidates for drug development for cardiovascular, inflammatory and neurodegenerative diseases.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Superoxide dismutases.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Peroxynitrite, a stealthy biological oxidant.

              Peroxynitrite is the product of the diffusion-controlled reaction of nitric oxide and superoxide radicals. Peroxynitrite, a reactive short-lived peroxide with a pKa of 6.8, is a good oxidant and nucleophile. It also yields secondary free radical intermediates such as nitrogen dioxide and carbonate radicals. Much of nitric oxide- and superoxide-dependent cytotoxicity resides on peroxynitrite, which affects mitochondrial function and triggers cell death via oxidation and nitration reactions. Peroxynitrite is an endogenous toxicant but is also a cytotoxic effector against invading pathogens. The biological chemistry of peroxynitrite is modulated by endogenous antioxidant mechanisms and neutralized by synthetic compounds with peroxynitrite-scavenging capacity.
                Bookmark

                Author and article information

                Contributors
                Journal
                Redox Biol
                Redox Biol
                Redox Biology
                Elsevier
                2213-2317
                19 September 2017
                April 2018
                19 September 2017
                : 14
                : 618-625
                Affiliations
                [a ]Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Avda. General Flores 2125, Montevideo 11800, Uruguay
                [b ]Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Avda. General Flores 2125, Montevideo 11800, Uruguay
                Author notes
                [* ]Corresponding author at: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Avda. General Flores 2125, Montevideo 11800, Uruguay.Departamento de Bioquímica, Facultad de Medicina, Universidad de la RepúblicaAvda. General Flores 2125Montevideo11800Uruguay sbartesa@ 123456fmed.edu.uy rradi@ 123456fmed.edu.uy
                Article
                S2213-2317(17)30621-3
                10.1016/j.redox.2017.09.009
                5694970
                29154193
                4d699c45-c6dd-4f6b-a5c8-417551932d5c
                © 2017 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 16 August 2017
                : 6 September 2017
                : 15 September 2017
                Categories
                Review Article

                free radicals,oxidants,nitric oxide,peroxynitrite and tyrosine nitration

                Comments

                Comment on this article