Convergence of biological nitration and nitrosation via symmetrical nitrous anhydride
Open accessAbstract
The current perspective holds that the generation of secondary signaling mediators from nitrite (NO2(-)) requires acidification to nitrous acid (HNO2) or metal catalysis. Herein, the use of stable isotope-labeled NO2(-) and LC-MS/MS analysis of products reveals that NO2(-) also participates in fatty acid nitration and thiol S-nitrosation at neutral pH. These reactions occur in the absence of metal centers and are stimulated by autoxidation of nitric oxide ((•)NO) via the formation of symmetrical dinitrogen trioxide (nitrous anhydride, symN2O3). Although theoretical models have predicted physiological symN2O3 formation, its generation is now demonstrated in aqueous reaction systems, cell models and in vivo, with the concerted reactions of (•)NO and NO2(-) shown to be critical for symN2O3 formation. These results reveal new mechanisms underlying the NO2(-) propagation of (•)NO signaling and the regulation of both biomolecule function and signaling network activity via NO2(-)-dependent nitrosation and nitration reactions.
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There exists a broad range of redox-derived nitrogen oxides that exert both cGMP-dependent and -independent signaling actions as a result of nitrosative-, nitrative- and oxidative-induced post-translational protein modifications and subsequent changes in protein function and gene expression profiles.
“There exists a broad range of redox-derived nitrogen oxides that exert both cGMP-dependent and -independent signaling actions as a result of nitrosative-, nitrative- and oxidative-induced post-translational protein modifications and subsequent changes in protein function and gene expression profiles[100–102].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [102]
H2S directly interfaces with nitrogen oxide reduction and the generation of intestinal NO by serving as an electron donor during nitrite reduction to NO by nitrite reductase, or by reacting with the nitrogen oxide S-nitrosothiol.
“H2S directly interfaces with nitrogen oxide reduction and the generation of intestinal NO by serving as an electron donor during nitrite reduction to NO by nitrite reductase, or by reacting with the nitrogen oxide S-nitrosothiol[91,102,346].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [102]
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- Authors
- Vitturi, D. A., Minarrieta, L., Salvatore, S. R., Postlethwait, E. M., Fazzari, M., Ferrer-Sueta, G., Lancaster, J. R., Freeman, B. A., & Schopfer, F. J.
- Affiliations
- University of Pittsburgh (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Schopfer, Francisco J
- Venue
- Nature Chemical Biology
- Published
- 2015-05-25
- Volume
- 11
- Issue
- 7
- Pages
- 504-510
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC4472503
- OpenAlex
- W1545999232
- Cited by
- 65
- References
- 53
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 9 · 2020: 3 · 2019: 10 · 2018: 13 · 2017: 8 · 2016: 3 · 2015: 3
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL064937, R37HL058115, R01HL058115, P01HL103455, R01HL132550)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072506)
- National Center for Complementary and Integrative Health (R01AT006822)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- nitrite, nitric oxide, dinitrogen trioxide, nitrosation, no-signaling
- MeSH terms
- Animals, Cell Line, Glutathione, Hydrogen-Ion Concentration, Inflammation, Kinetics, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Nitrates, Nitric Oxide, Nitrites, Nitrogen Isotopes, Nitrogen Oxides, Nitrous Acid, Oxygen Isotopes, Nitrosation, Linoleic Acids, Conjugated, Mice
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