The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine
Open accessAbstract
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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Nitrite and Nitrate as a Treatment for Hypertension
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“Nitrate and nitrite concentrations were measured in the cell culture supernatants by ozone-based chemiluminescence (model 88 AM, Eco Physics) as previously described [12, 13].”
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“This means that NO concentration = 300 µM (9 ppm) in the presence of oxygen has a half-life of < 1 s (Ignarro et al. 1993), well within the transit time of the experimental filter system and certainly within the retention time after initial adsorption onto the moist filter coating surface.”
Санина, Н. А., Konyukhova, A. S., Корчагин, Д. В., Ovanesyan, N. S., Куликов, А. В., Mumyatova, V. A., Терентьев, А. А., & Aldoshin, S. M. (2023) · Журнал неорганической химии · doi:10.31857/s0044457x23600664
The nitrite reductase activity of xanthine oxidoreductase sustains cardiovascular healthPreprint
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“The nitrite (NO₂), a metabolite of nitric oxide, was quantified by monitoring the conversion of nitrate (NO₃) to NO₂ via NO₃ reductase and analyzed using the colorimetric Griess Reaction [19].”
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“This is further compounded by the high reactivity of NO itself, which undergoes rapid oxidation to nitrite (NO₂⁻) under physiological conditions [ 32 ].”
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“Note that this oxidation is very slow in aqueous solution without the presence of oxidizing agent such as oxyhemoglobine, hydroxyl radical, or superoxide [70,419].”
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Xu, M., Pan, Y. W., Wang, J., Li, S., Zhai, D., Liu, H., Li, H. C., Deng, W., Sun, L., & Yang, L. (2026) · Journal of Materials Chemistry A · doi:10.1039/d6ta03008d
Lee, J. Y., Lee, M., Yoon, S., Song, M. J., & Yoon, S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.12.738090
“Moreover, the rapid abiotic oxidation of NO by O 2 provides a chemically plausible mechanism for the simultaneous formation of both NO 2 ⁻ and NO 3 ⁻ 15 .”
Pokidova, O. V., Ruina, K. S., Novikova, V. O., Emel’yanova, N. S., Psikha, B. L., Kulikov, A. V., & Санина, Н. А. (2026) · Russian Chemical Bulletin · doi:10.1007/s11172-026-4994-2
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“It has been reported that the reaction between NO and dissolved O 2 at near-ambient temperature predominantly yields nitrite [52], while the formation of NO 2 and subsequently nitrate requires an elevated temperature and/or a suitable catalyst [52, 53].”
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Altitude ascent: Exploring the unknown terrain of women’s reproductive health
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Regulation of Gene Expression by Nitric Oxide
Deora, A. A., & Lander, H. M. (2000) · doi:10.1007/978-1-59259-002-5_4
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Arif, S. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
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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