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Cited by 216Hemoglobin structure and functionNitric Oxide and Endothelin EffectsHeme Oxygenase-1 and Carbon Monoxide

Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions

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Joshi, Mahesh S., Ferguson, T. Bruce, Han, Tae H., Hyduke, Daniel R., Liao, James C., Rassaf, Tienush, Bryan, Nathan, Feelisch, Martin +1 more·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.152149699PMC PMC124916
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Abstract

Although irreversible reaction of NO with the oxyheme of hemoglobin (producing nitrate and methemoglobin) is extremely rapid, it has been proposed that, under normoxic conditions, NO binds preferentially to the minority deoxyheme to subsequently form S-nitrosohemoglobin (SNOHb). Thus, the primary reaction would be conservation, rather than consumption, of nitrogen oxide. Data supporting this conclusion were generated by using addition of a small volume of a concentrated aqueous solution of NO to a normoxic hemoglobin solution. Under these conditions, however, extremely rapid reactions can occur before mixing. We have thus compared bolus NO addition to NO generated homogeneously throughout solution by using NO donors, a more physiologically relevant condition. With bolus addition, multiple hemoglobin species are formed (as judged by visible spectroscopy) as well as both nitrite and nitrate. With donor, only nitrate and methemoglobin are formed, stoichiometric with the amount of NO liberated from the donor. Studies with increasing hemoglobin concentrations reveal that the nitrite-forming reaction (which may be NO autoxidation under these conditions) competes with reaction with hemoglobin. SNOHb formation is detectable with either bolus or donor; however, the amounts formed are much smaller than the amount of NO added (less than 1%). We conclude that the reaction of NO with hemoglobin under normoxic conditions results in consumption, rather than conservation, of NO.

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  • Oxygenated hemoglobin is an extremely effective NO scavenger that reacts rapidly with NO to form nitrate and methemoglobin.

    “Oxygenated hemoglobin is an extremely effective NO scavenger that reacts rapidly with NO to form nitrate and methemoglobin (met-Hb) [105].”

    From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [105]

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Authors
Joshi, M. S., Ferguson, T. B., Han, T. H., Hyduke, D. R., Liao, J. C., Rassaf, T., Bryan, N., Feelisch, M., & Lancaster, J. R.
Affiliations
University of California, Los Angeles (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2002-07-17
Volume
99
Issue
16
Pages
10341-10346
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.152149699
PMC
PMC124916
OpenAlex
W2056150843
Cited by
216
References
50
Citations by year
2026: 4 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 1 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 8 · 2013: 10 · 2012: 13
FWCI
8.49
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
Funders
  • National Institutes of Health (5r01hl060302-03)
  • National Heart, Lung, and Blood Institute (R01HL065741, HL60302, HL65741, R01HL069029)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 46935, R01DK046935)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
nitric oxide, oxyhemoglobin, S-nitrosohemoglobin, nitric oxide consumption, methemoglobin, nitrate formation, nitrite production, nitric oxide donors
MeSH terms
Hemoglobins, Humans, Nitric Oxide, Oxyhemoglobins

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