Cited by 856Nitric Oxide and Endothelin EffectsHemoglobin structure and functionRedox biology and oxidative stress

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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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Ignarro, L J, Fukuto, J M, Griscavage, J M, Rogers, N E, Byrns, R E·1993·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.90.17.8103PMC PMC47296

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Abstract

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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L-Arginine as a Potential Ergogenic Aid in Healthy Subjects
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Background
Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α
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Thalidomide Inhibits Tumor Necrosis Factor α, Decreases Nitric Oxide Synthesis, and Ameliorates the Hyperdynamic Circulatory Syndrome in Portal–Hypertensive Rats
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Nitrotyrosine in plasma of celiac disease patients as detected by a new sandwich ELISA
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The role of the reactions of ·NO with superoxide and oxygen in biological systems: A kinetic approach
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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
DOI: 10.1073/pnas.90.17.8103
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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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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