The oxyhemoglobin reaction of nitric oxide

Andrew J. Gow, Benjamin P. Luchsinger, John R. Pawloski, David J. Singel, Jonathan S. Stamler

Research output: Contribution to journalArticle

350 Citations (Scopus)

Abstract

The oxidation of nitric oxide (NO) to nitrate by oxyhemoglobin is a fundamental reaction that shapes our understanding of NO biology. This reaction is considered to be the major pathway for NO elimination from the body; it is the basis for a prevalent NO assay; it is a critical feature in the modeling of NO diffusion in the circulatory system; and it informs a variety of therapeutic applications, including NO-inhalation therapy and blood substitute design. Here we show that, under physiological conditions, this reaction is of little significance. Instead, NO preferentially binds to the minor population of the hemoglobin's vacant hemes in a cooperative manner, nitrosylates hemoglobin thiols, or reacts with liberated superoxide in solution. In the red blood cell, superoxide dismutase eliminates superoxide, increasing the yield of S-nitrosohemoglobin and nitrosylated hemes. Hemoglobin thus serves to regulate the chemistry of NO and maintain it in a bioactive state. These results represent a reversal of the conventional view of hemoglobin in NO biology and motivate a reconsideration of fundamental issues in NO biochemistry and therapy.

Original languageEnglish
Pages (from-to)9027-9032
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number16
DOIs
Publication statusPublished - 3 Aug 1999
Externally publishedYes

Fingerprint

Oxyhemoglobins
Nitric Oxide
Hemoglobins
Heme
Superoxides
Blood Substitutes
Respiratory Therapy
Cardiovascular System
Sulfhydryl Compounds
Biochemistry
Nitrates
Superoxide Dismutase
Erythrocytes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Gow, A. J., Luchsinger, B. P., Pawloski, J. R., Singel, D. J., & Stamler, J. S. (1999). The oxyhemoglobin reaction of nitric oxide. Proceedings of the National Academy of Sciences of the United States of America, 96(16), 9027-9032. https://doi.org/10.1073/pnas.96.16.9027

The oxyhemoglobin reaction of nitric oxide. / Gow, Andrew J.; Luchsinger, Benjamin P.; Pawloski, John R.; Singel, David J.; Stamler, Jonathan S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 16, 03.08.1999, p. 9027-9032.

Research output: Contribution to journalArticle

Gow, AJ, Luchsinger, BP, Pawloski, JR, Singel, DJ & Stamler, JS 1999, 'The oxyhemoglobin reaction of nitric oxide', Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 16, pp. 9027-9032. https://doi.org/10.1073/pnas.96.16.9027
Gow, Andrew J. ; Luchsinger, Benjamin P. ; Pawloski, John R. ; Singel, David J. ; Stamler, Jonathan S. / The oxyhemoglobin reaction of nitric oxide. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 16. pp. 9027-9032.
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