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Cited by 334Hemoglobin structure and functionMetal-Catalyzed Oxygenation MechanismsNitric Oxide and Endothelin Effects

Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites.

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Doyle, M.P., Pickering, R.A., DeWeert, T.M., Hoekstra, J.W., Pater, D.·1981·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(18)43285-1
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Abstract

The reactions of human hemoglobin with sodium nitrite and ethyl nitrite in deoxygenated media have been examined in kinetic detail. Nitrous acid has been identified from kinetic pH dependence studies as the principal oxidant of hemoglobin in reactions with sodium nitrite. Nitrosylhemoglobin is produced concurrently with methemoglobin as a result of reductive release of nitric oxide from nitrous acid. However, oxidation of hemoglobin by nitric oxide competes with association, and this process is proposed to arise from the action of the nitric oxide dimer on hemoglobin. Ethyl nitrite, which serves as a model for nitrous acid, reacts with hemoglobin at rates that are at least 10 times slower than those extrapolated for nitrous acid, and hydrolysis of the alkyl nitrite is not competitive with oxidation of hemoglobin. The composite experimental results are interpreted to describe alkyl nitrite, and, presumably, nitrous acid association with hemoglobin followed by rate-limiting electron transfer resulting in nitric oxide and alkoxide (or hydroxide) production. Proton transfer resulting in alcohol (or water) formation occurs subsequent to the rate-limiting step as do reactions of hemoglobin with nitric oxide.

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Crossref · 10.1016/s0021-9258(18)43285-1

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37 of 37 references verified0 citation errors · 0 not checkable

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  • The reaction of nitrite with deoxyHb requires a proton and formally requires nitrous acid, making it faster at low pH.

    “By studying the same reaction using alkyl nitrites, which do not show a pH dependence in their reaction rates with deoxyHb, it was established that the reaction of nitrite requires a proton and thus formally requires nitrous acid (247, 248). This property also makes the reaction faster in low pH conditions.”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [248]

  • The scheme of heme protein-mediated nitrite reduction applies to virtually all heme proteins studied to date, including Hb, Mb, Ngb, Cygb, CBS, globin X, plant and cyanobacterial Hb, flavohemoglobin, heme-albumin, cytochrome c, protoglobin, and microperoxidase-11.

    “This scheme has been found to apply to virtually all the heme protein–mediated nitrite reduction reactions studied to date, including Hb (248, 447), Mb (247, 862), neuroglobin (Ngb) (932, 945), Cygb (182, 571, 780), cystathionine β-synthase (CBS) (149, 350), globin X (184), plant and cyanobacterial Hb (phytohemoglobins) (905, 946), flavohemoglobin (340), heme-albumin (43), cytochrome c (41), prot”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [248]

  • In the acute setting, nitrite can bind to hemoglobin and oxidize the ferrous iron in heme to the ferric state, forming methemoglobin and preventing the binding of oxygen.

    “In the acute setting, nitrite can bind to hemoglobin and oxidize the ferrous iron in heme to the ferric state, thereby forming methemoglobin (metHgb) and preventing the binding of oxygen[152].”

    From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [152]

  • The reduction of nitrite by Hb occurs as NO2− + HbFe2+ + H+ → NO + HbFe3+ + OH−.

    “(1)NO2−+HbFe2++H+→NO+HbFe3++OH−”

    From Mechanisms of nitrite bioactivation (2014) · cites this paper as [35]

  • Doyle and colleagues found k0 for Hb to be 12.3 × 10^3 M−1s−1.

    “Doyle and colleagues found k0 to be 12.3 × 103 M−1s−1 [35].”

    From Mechanisms of nitrite bioactivation (2014) · cites this paper as [35]

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Authors
Doyle, M. P., Pickering, R. A., DeWeert, T. M., Hoekstra, J. W., & Pater, D.
Affiliations
Hope College (US)
ORCID
Doyle, M.P.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1981-12
Volume
256
Issue
23
Pages
12393-12398
ISSN
0021-9258 (ISSN-L)
DOI
10.1016/s0021-9258(18)43285-1
OpenAlex
W1589586351
Cited by
334
References
37
Citations by year
2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 2 · 2021: 10 · 2020: 4 · 2019: 8 · 2018: 12 · 2017: 7 · 2016: 12 · 2015: 18 · 2014: 16 · 2013: 11 · 2012: 12
FWCI
0.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
nitrous acid, sodium nitrite, ethyl nitrite, nitric oxide, nitrosylhemoglobin, methemoglobin, nitric oxide dimer, electron transfer, reaction mechanism, reaction kinetics, proton transfer
MeSH terms
Hemoglobin A, Humans, Hydrogen-Ion Concentration, Kinetics, Nitrites, Oxidation-Reduction, Oxyhemoglobins, Sodium Nitrite, Spectrophotometry

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