Endothelial nitric oxide synthase reduces nitrite anions to NO under anoxia

Gautier, Clément; van Faassen, Ernst; Mikula, Ivan; Martasek, Pavel; Slama-Schwok, Anny

doi:10.1016/j.bbrc.2006.01.031

Cited by 143Nitric Oxide and Endothelin EffectsHemoglobin structure and functionMetal-Catalyzed Oxygenation Mechanisms

Endothelial nitric oxide synthase reduces nitrite anions to NO under anoxia

Gautier, Clément, van Faassen, Ernst, Mikula, Ivan, Martasek, Pavel, Slama-Schwok, Anny·2006·Biochemical and Biophysical Research Communications

DOI 10.1016/j.bbrc.2006.01.031

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Abstract

In this work, we demonstrate that endothelial nitric oxide synthase is capable of anoxic reduction of nitrite anions to nitric oxide at physiological pH by absorption and EPR spectroscopy and electrochemical measurements. The nitrite reduction is achieved at the oxygenase domain of the protein and proceeds even in the absence of the tetrahydrobiopterin cofactor. The nitrite pathway increases by sixfold the NO production with respect to the regular arginine pathway under hypoxia, which is largely blocked. Therefore, basal levels of NO release could be sustained by anoxic nitrite reduction. The reaction suggests a new pathway for fast NO delivery under hypoxia, precisely when the vasodilating properties of nitric oxide are most needed.

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Endothelial NOS has been shown to be capable of reducing nitrite to NO.
“Endothelial NOS has also been shown to be capable of reducing nitrite to NO [81–83].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [81]
Nitrite reduction by eNOS is most effective in the presence of calcium/calmodulin, tetrahydrobiopterin, and arginine, and is suggested to involve an additional active site besides the heme.
“Nitrite reduction is most effective in the presence of calcium/calmodulin, tetrahydrobiopterin, and arginine, and is suggested to involve an additional active site besides the heme [81].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [81]

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Nitric oxide synthase reduces nitrite to NO under anoxia
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Enhanced release of nitric oxide from endothelial cells under anoxia
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Isoform-specific differences in the nitrite reductase activity of nitric oxide synthases under hypoxia
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Mechanisms Underlying Erythrocyte and Endothelial Nitrite Reduction to Nitric Oxide in Hypoxia: Role for Xanthine Oxidoreductase and Endothelial Nitric Oxide Synthase
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Generation of Nitric Oxide by a Nitrite Reductase Activity of Xanthine Oxidase: A Potential Pathway for Nitric Oxide Formation in the Absence of Nitric Oxide Synthase Activity
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Authors: Gautier, C., van Faassen, E., Mikula, I., Martasek, P., & Slama-Schwok, A.
Affiliations: Centre National de la Recherche Scientifique (FR)
Charles University (CZ)
ORCID: Mikula, Ivan
Venue: Biochemical and Biophysical Research Communications
Publisher: Elsevier BV
Published: 2006-03
Volume: 341
Issue: 3
Pages: 816-821
ISSN: 0006-291X (ISSN-L)
DOI: 10.1016/j.bbrc.2006.01.031
OpenAlex: W2116948662
Cited by: 143
References: 32
Citations by year: 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 4 · 2018: 14 · 2017: 5 · 2016: 5 · 2015: 10 · 2014: 5 · 2013: 14 · 2012: 9
FWCI: 8.40
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochemical and Biophysical Research Communications (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
Keywords: endothelial nitric oxide synthase, nitrite reduction, nitric oxide production, anoxia, hypoxia, oxygenase domain, tetrahydrobiopterin, vasodilation
MeSH terms: Anaerobiosis, Anions, NADP, Nitric Oxide, Nitrites, Oxidation-Reduction, Oxygen, Oxygenases, Spectrum Analysis, Cell Hypoxia, Nitric Oxide Synthase Type III

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Endothelial nitric oxide synthase reduces nitrite anions to NO under anoxia

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