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Biochemistry of Nitric Oxide and Peroxynitrite: Sources, Targets and Biological Implications

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Biochemistry of Oxidative Stress

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 16))

Abstract

Nitric oxide (•NO) is a relatively stable free radical generated biologically that participates in a series of signal transducing and physiological processes in human biology. Enzymatic as well as non-enzymatic sources of •NO have been reported in vivo. In circumstances where •NO is overproduced and/or in the context of a pro-oxidant environment, it can turn into a toxic molecule and converts into a pathogenic mediator in human diseases. In particular, the diffusion-controlled reaction of •NO with superoxide radical anion (O2 •−) leads to the formation of peroxynitrite (ONOO−), a strong oxidant and nucleophile that mediates much of the toxicity associated to •NO. Peroxynitrite promotes one- and two-electron oxidations and nitration reactions via a series of mechanisms several of which involve free radical intermediates. In this chapter we summarize key biochemical aspects concerning the mechanisms of formation of •NO, peroxynitrite and other reactive nitrogen species (RNS), their reaction with biomolecular targets and participation in the development of pathologies. In addition, we critically analyze current redox-based therapeutic strategies including the direct action of compounds on •NO-and peroxynitrite-derived reactive species as well as the induction or endogenous antioxidant mechanisms, with the overall goal to cope against nitroxidative stress conditions.

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Acknowledgements

This work was supported by grants from Universidad de la República (CSIC and Espacio Interdisciplinario). Additional funding was obtained from PEDECIBA. A. Aicardo, D. M. Martinez and N. Campolo have been supported by fellowships of Agencia Nacional de Investigación e Innovación (ANII, Uruguay), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Universidad de la República (CAP), respectively.

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  1. Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay

    Adrián Aicardo, Débora M. Martinez, Nicolás Campolo, Silvina Bartesaghi & Rafael Radi

  2. Departamento de Educacion Médica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay

    Silvina Bartesaghi

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  2. Débora M. Martinez
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  3. Nicolás Campolo
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  4. Silvina Bartesaghi
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  5. Rafael Radi
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Correspondence to Rafael Radi .

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Editors and Affiliations

  1. School of Medicine, University of Buenos Aires, Buenos Aires, Argentina

    Ricardo Jorge Gelpi

  2. School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

    Alberto Boveris

  3. Instituto de Inmunología, Genética y Metabolismo (INIGEM, UBA–CONICET), Laboratorio de Metabolismo del Oxígeno, Hospital Universitario, Universidad de Buenos Aires, Buenos Aires, Argentina

    Juan José Poderoso

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Aicardo, A., Martinez, D.M., Campolo, N., Bartesaghi, S., Radi, R. (2016). Biochemistry of Nitric Oxide and Peroxynitrite: Sources, Targets and Biological Implications. In: Gelpi, R., Boveris, A., Poderoso, J. (eds) Biochemistry of Oxidative Stress. Advances in Biochemistry in Health and Disease, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-45865-6_5

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