Pathophysiology of nitric oxide and related species: Free radical reactions and modification of biomolecules

Jason P. Eiserich, Rakesh P. Patel, Valerie B. O'Donnell

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

Abstract

Since its initial discovery as an endogenously produced bioactive mediator, nitric oxide (.NO) has been found to play a critical role in the cellular function of nearly all organ systems. Furthermore, aberrant production of .NO or reactive nitrogen species (RNS) derived from .NO, has been implicated in a number of pathological conditions, such as acute lung disease, atherosclerosis and septic shock. While .NO itself is fairly non-toxic, secondary RNS are oxidants and nitrating agents that can modify both the structure and function of numerous biomolecules both in vitro, and in vivo. The mechanisms by which RNS mediate toxicity are largely dictated by its unique reactivity. The study of how reactive nitrogen species (RNS) derived from .NO interact with biomolecules such as proteins, carbohydrates and lipids, to modify both their structure and function is an area of active research, which is lending major new insights into the mechanisms underlying their pathophysiological role in human disease. In the context of .NO-dependent pathophysiology, these biochemical reactions will play a major role since they: (i) lead to removal of .NO and decreased efficiency of .NO as an endothelial-derived relaxation factor (e.g. in hypertension, atherosclerosis) and (ii) lead to production of other intermediate species and covalently modified biomolecules that cause injury and cellular dysfunction during inflammation. Although the physical and chemical properties of .NO and .NO-derived RNS are well characterised, extrapolating this fundamental knowledge to a complicated biological environment is a current challenge for researchers in the field of .NO and free radical research. In this review, we describe the impact of .NO and .NO-derived RNS on biological processes primarily from a biochemical standpoint. In this way, it is our intention to outline the most pertinent and relevant reactions of RNS, as they apply to a diverse array of pathophysiological states. Since reactions of RNS in vivo are likely to be vast and complex, our aim in this review is threefold: (i) address the major sources and reactions of .NO derived RNS in biological systems, (ii) describe current knowledge regarding the functional consequences underlying .NO-dependent covalent modification of specific biomolecules, and (iii) to summarise and critically evaluate the available evidence implicating these reactions in human pathology. To this end, three areas of special interest have been chosen for detailed description, namely, formation and role of S-nitrosothiols, modulation of lipid oxidation/nitration by RNS, and tyrosine nitration mechanisms and consequences.

Original languageEnglish (US)
Pages (from-to)221-357
Number of pages137
JournalMolecular Aspects of Medicine
Volume19
Issue number4-5
DOIs
StatePublished - Aug 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine

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