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Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine
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Nitric oxide (NO) in oxygen-containing aqueous solution has a short half-life that is often attributed to a rapid oxidation to both NO2- and NO3-. The chemical fate of NO in aqueous solution is often assumed to be the same as that in air, where NO is oxidized to NO2 followed by dimerization to N2O4. Water then reacts with N2O4 to form both NO2- and NO3-. We report here that NO in aqueous solution containing oxygen is oxidized primarily to NO2- with little or no formation of NO3-. In the presence of oxyhemoglobin or oxymyoglobin, however, NO and NO2- were oxidized completely to NO3-. Methemoglobin was inactive in this regard. The unpurified cytosolic fraction from rat cerebellum, which contains constitutive NO synthase activity, catalyzed the conversion of L-arginine primarily to NO3- (NO2-/NO3- ratio = 0.25). After chromatography on DEAE-Sephacel or affinity chromatography using 2',5'-ADP-Sepharose 4B, active fractions containing NO synthase activity catalyzed the conversion of L-arginine primarily to NO2- (NO2-/NO3- ratio = 5.6) or only to NO2-, respectively. Unpurified cytosol from activated rat alveolar macrophages catalyzed the conversion of L-arginine to NO2- without formation of NO3-. Addition of 30 microM oxyhemoglobin to all enzyme reaction mixtures resulted in the formation primarily of NO3- (NO2-/NO3- ratio = 0.09 to 0.20). Cyanide ion, which displaces NO2- from its binding sites on oxyhemoglobin, inhibited the formation of NO3-, thereby allowing NO2- to accumulate. These observations indicate clearly that the primary decomposition product of NO in aerobic aqueous solution is NO2- and that further oxidation to NO3- requires the presence of additional oxidizing species such as oxyhemoproteins.
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“This report clearly demonstrated that the dominant oxidation product of NO in aqueous solution is nitrite and that nitrate formation requires additional oxidation by heme proteins.”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [76]
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A Rapid, Simple Spectrophotometric Method for Simultaneous Detection of Nitrate and Nitrite
Miranda, K. M., Espey, M. G., & Wink, D. A. (2001) · Nitric Oxide · doi:10.1006/niox.2000.0319 · Cited by 3,858
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“NO formed in the endothelium from the amino acid precursor L-arginine by the activity of the constitutive endothelial NOS isoenzymes has been shown to play an important role in the regulation of local vasomotor tone and other vascular roles and is thought, on the other hand to be due to transcriptional diversity (Igna…”
BackgroundInfluentialDetection and Imaging of Nitric Oxide with Novel Fluorescent Indicators: Diaminofluoresceins
Kojima, H., Nakatsubo, N., Kikuchi, K., Kawahara, S., Kirino, Y., Nagoshi, H., Hirata, Y., & Nagano, T. (1998) · Analytical Chemistry · doi:10.1021/ac9801723 · Cited by 1,391
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Methods to detect nitric oxide and its metabolites in biological samples
Bryan, N. S., & Grisham, M. B. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.04.026 · Cited by 1,005
“, suggests that the NO2 – derived from NO autoxidation is rapidly converted to NO3 – via its oxidation by certain oxyhemoproteins (P–FeO2) such as oxyhemoglobin or oxymyoglobin [14]: 2P–Fe2þO2 þ 3NO2 þ 2Hþ → 2P–Fe3þ þ 3NO3 þ H2O ð4Þ”
Metadata
- Authors
- Ignarro, L. J., Fukuto, J. M., Griscavage, J. M., Rogers, N. E., & Byrns, R. E.
- Affiliations
- University of California, Los Angeles (US)
- ORCID
- Fukuto, J M
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1993-09
- Volume
- 90
- Issue
- 17
- Pages
- 8103-8107
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC47296
- OpenAlex
- W2033379487
- Cited by
- 856
- References
- 28
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 19 · 2023: 21 · 2022: 14 · 2021: 15 · 2020: 21 · 2019: 19 · 2018: 20 · 2017: 21 · 2016: 18 · 2015: 23 · 2014: 28 · 2013: 27 · 2012: 24
- FWCI
- 17.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl040922-11, 5r01hl046388-03, 5r01hl035014-12)
- National Heart, Lung, and Blood Institute (HL 46388, HL-35014, HL 40922)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- NO oxidation, nitrite, nitrate, aqueous solutions, oxyhemoglobin, oxymyoglobin, methemoglobin, nitric oxide synthase, L-arginine, alveolar macrophages, cyanide, heme proteins
- MeSH terms
- Amino Acid Oxidoreductases, Animals, Arginine, Hemeproteins, Humans, Kinetics, Methemoglobin, Myoglobin, Nitrates, Nitric Oxide, Nitrites, Oxidation-Reduction, Oxyhemoglobins, Solutions, Nitric Oxide Synthase
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