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Cited by 86Hemoglobin structure and functionNitric Oxide and Endothelin EffectsHeme Oxygenase-1 and Carbon Monoxide

S-Nitrosohemoglobin: a mechanism for its formation in conjunction with nitrite reduction by deoxyhemoglobin

Nagababu, Enika, Ramasamy, Somasundaram, Rifkind, Joseph M.·2006·Nitric Oxide
DOI 10.1016/j.niox.2006.01.012
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Abstract

The formation of S-nitrosohemoglobin (SNOHb) in red cells has been a major point of contention among researchers in this field. We have delineated a new mechanism for the formation of SNOHb coupled to nitrite reduction by deoxygenated hemoglobin chains at low oxygen pressures. The establishment of this mechanism required the development of a chemiluminescence assay utilizing Cu(II) and ascorbic acid to directly measure nitrosothiols without any interference from nitrite or heme-NO. The formation of SNOHb was shown to involve a dominant nitrite-reduction intermediate with electron delocalized between the heme iron and the bound NO. The possible mechanisms for the formation of SNOHb from this intermediate in the absence of oxygen are discussed including the role for an expansion of the electron delocalized intermediate to include the beta-93 cysteine residue. This extended delocalization was supported by a direct reaction with unbound NO, simultaneously producing SNOHb and Hb(II)NO, when NO reacts with metHb. The SNOHb found in red cells in vivo can, thus, be explained as originating from nitrite reduction that takes place at reduced oxygen pressures.

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  • Several proposed mechanisms explain how nitrite-derived bioactivity can be exported from the red blood cell, generally involving either a compartment model with submembrane localization or formation of another nitrogen oxide such as a nitrosothiol or N2O3.

    “Several proposed mechanisms have been constructed to explain how nitrite-derived bioactivity can be exported from the red blood cell and these generally involve either a compartment model with submembrane localization of the reaction allowing for inefficient free NO escape, or the formation of another nitrogen oxide such as a nitrosothiol or N2O3 that can get out of the red blood cell and carry NO”

    From Mechanisms of nitrite bioactivation (2014) · cites this paper as [48]

  • Exogenous administration of nitrite correlates with increased levels of S-nitrosothiols in red blood cells and other tissues both in vivo and in vitro.

    “exogenous administration of nitrite correlates with increased levels of S-nitrosothiols in red blood cells and other tissues both in vivo and in vitro [25, 43, 46-53].”

    From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [49]

  • Nitrite supplementation to intact organisms is associated with a widespread increase in the concentration of nitrite and production of NO-derived species such as S-nitrosothiols or nitrosylhemes in several tissues.

    “Many reports show that nitrite supplementation to intact organisms is associated with a widespread increase in the concentration of this anion and production of NO-derived species such as S-nitrosothiols or nitrosylhemes in several tissues[25, 43, 46, 48, 49, 96].”

    From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [49]

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Authors
Nagababu, E., Ramasamy, S., & Rifkind, J. M.
Affiliations
National Institutes of Health (US)
Corresponding author
Rifkind, Joseph M.
Venue
Nitric Oxide
Publisher
Elsevier BV
Published
2006-08
Volume
15
Issue
1
Pages
20-29
ISSN
1089-8603 (ISSN-L)
DOI
10.1016/j.niox.2006.01.012
OpenAlex
W2075876421
Cited by
86
References
60
Citations by year
2024: 5 · 2022: 2 · 2021: 1 · 2020: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2014: 5 · 2013: 5 · 2012: 4
FWCI
5.24
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Nitric Oxide (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
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
S-nitrosohemoglobin, nitrite reduction, deoxyhemoglobin, S-nitrosothiols, chemiluminescence assay, electron delocalization, erythrocytes, low oxygen pressure
MeSH terms
Erythrocytes, Heme, Hemoglobins, Humans, Luminescent Measurements, Nitric Oxide, Nitrites, Oxidation-Reduction, S-Nitrosothiols

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