Hemoglobin-mediated nitric oxide signaling
Open accessAbstract
The rate that hemoglobin reacts with nitric oxide (NO) is limited by how fast NO can diffuse into the heme pocket. The reaction is as fast as any ligand/protein reaction can be and the result, when hemoglobin is in its oxygenated form, is formation of nitrate in what is known as the dioxygenation reaction. As nitrate, at the concentrations made through the dioxygenation reaction, is biologically inert, the only role hemoglobin was once thought to play in NO signaling was to inhibit it. However, there are now several mechanisms that have been discovered by which hemoglobin may preserve, control, and even create NO activity. These mechanisms involve compartmentalization of reacting species and conversion of NO from or into other species such as nitrosothiols or nitrite which could transport NO activity. Despite the tremendous amount of work devoted to this field, major questions concerning precise mechanisms of NO activity preservation as well as if and how Hb creates NO activity remain unanswered.
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Hemoglobin rapidly inactivates the NO signal by binding NO to the oxygenated Fe2+-heme metal center, followed by formation of methemoglobin and nitrate with a high reaction constant of ≈6-8 × 107 M−1s−1.
“Hb is thought to rapidly inactivate the NO signal by binding NO to the oxygenated Fe2+-heme metal center, which is followed by subsequent formation of metHb and nitrate with a high reaction constant of ≈6–8 × 107 M−1s−1 (Eq. 15) (81).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [81]
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References 155 · Cited by 146
Research works printed but not linked: 14
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- Authors
- Helms, C., & Kim-Shapiro, D. B.
- Affiliations
- Wake Forest University (US)
- ORCID
- Helms, Christine
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 61
- Pages
- 464-472
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC3849136
- OpenAlex
- W2022734495
- Cited by
- 146
- References
- 155
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 12 · 2023: 20 · 2022: 14 · 2021: 11 · 2020: 11 · 2019: 14 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 3 · 2013: 4
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- supported by NIH (HL58091, HL098032 (D.K.-S.)
- 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
- hemoglobin, nitric oxide signaling, nitrate, S-nitrosothiols, nitrite
- MeSH terms
- Animals, Hemoglobins, Humans, Nitric Oxide, Nitrites, Oxidation-Reduction, Signal Transduction
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