Nitric oxide production from nitrite occurs primarily in tissues not in the blood: Critical role of xanthine oxidase and aldehyde oxidase

Haitao Li, Hongmei Cui, Tapan Kumar Kundu, Wael Alzawahra, Jay L. Zweier

Research output: Contribution to journalArticle

Abstract

Recent studies have shown that nitrite is an important storage form and source of NO in biological systems. Controversy remains, however, regarding whether NO formation from nitrite occurs primarily in tissues or in blood. Questions also remain regarding the mechanism, magnitude, and contributions of several alternative pathways of nitrite-dependent NO generation in biological systems. To characterize the mechanism and magnitude of NO generation from nitrite, electron paramagnetic resonance spectroscopy, chemiluminescence NO analyzer, and immunoassays of cGMP formation were performed. The addition of nitrite triggered a large amount of NO generation in tissues such as heart and liver, but only trace NO production in blood. Carbon monoxide increased NO release from blood, suggesting that hemoglobin acts to scavenge NO not to generate it. Administration of the xanthine oxidase (XO) inhibitor oxypurinol or aldehyde oxidase (AO) inhibitor raloxifene significantly decreased NO generation from nitrite in heart or liver. NO formation rates increased dramatically with decreasing pH or with decreased oxygen tension. Isolated enzyme studies further confirm that XO and AO, but not hemoglobin, are critical nitrite reductases. Overall, NO generation from nitrite mainly occurs in tissues not in the blood, with XO and AO playing critical roles in nitrite reduction, and this process is regulated by pH, oxygen tension, nitrite, and reducing substrate concentrations.

Original languageEnglish (US)
Pages (from-to)17855-17863
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number26
DOIs
StatePublished - Jun 27 2008
Externally publishedYes

Fingerprint

Aldehyde Oxidase
Xanthine Oxidase
Nitrites
Nitric Oxide
Blood
Tissue
Biological systems
Liver
Hemoglobins
Oxypurinol
Nitrite Reductases
Oxygen
Chemiluminescence
Electron Spin Resonance Spectroscopy
Carbon Monoxide
Luminescence
Immunoassay
Paramagnetic resonance
Spectrum Analysis
Spectroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Nitric oxide production from nitrite occurs primarily in tissues not in the blood : Critical role of xanthine oxidase and aldehyde oxidase. / Li, Haitao; Cui, Hongmei; Kundu, Tapan Kumar; Alzawahra, Wael; Zweier, Jay L.

In: Journal of Biological Chemistry, Vol. 283, No. 26, 27.06.2008, p. 17855-17863.

Research output: Contribution to journalArticle

Li, Haitao ; Cui, Hongmei ; Kundu, Tapan Kumar ; Alzawahra, Wael ; Zweier, Jay L. / Nitric oxide production from nitrite occurs primarily in tissues not in the blood : Critical role of xanthine oxidase and aldehyde oxidase. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 26. pp. 17855-17863.
@article{c4da7425a4cc48eb9bcbacec14582e0b,
title = "Nitric oxide production from nitrite occurs primarily in tissues not in the blood: Critical role of xanthine oxidase and aldehyde oxidase",
abstract = "Recent studies have shown that nitrite is an important storage form and source of NO in biological systems. Controversy remains, however, regarding whether NO formation from nitrite occurs primarily in tissues or in blood. Questions also remain regarding the mechanism, magnitude, and contributions of several alternative pathways of nitrite-dependent NO generation in biological systems. To characterize the mechanism and magnitude of NO generation from nitrite, electron paramagnetic resonance spectroscopy, chemiluminescence NO analyzer, and immunoassays of cGMP formation were performed. The addition of nitrite triggered a large amount of NO generation in tissues such as heart and liver, but only trace NO production in blood. Carbon monoxide increased NO release from blood, suggesting that hemoglobin acts to scavenge NO not to generate it. Administration of the xanthine oxidase (XO) inhibitor oxypurinol or aldehyde oxidase (AO) inhibitor raloxifene significantly decreased NO generation from nitrite in heart or liver. NO formation rates increased dramatically with decreasing pH or with decreased oxygen tension. Isolated enzyme studies further confirm that XO and AO, but not hemoglobin, are critical nitrite reductases. Overall, NO generation from nitrite mainly occurs in tissues not in the blood, with XO and AO playing critical roles in nitrite reduction, and this process is regulated by pH, oxygen tension, nitrite, and reducing substrate concentrations.",
author = "Haitao Li and Hongmei Cui and Kundu, {Tapan Kumar} and Wael Alzawahra and Zweier, {Jay L.}",
year = "2008",
month = "6",
day = "27",
doi = "10.1074/jbc.M801785200",
language = "English (US)",
volume = "283",
pages = "17855--17863",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "26",

}

TY - JOUR

T1 - Nitric oxide production from nitrite occurs primarily in tissues not in the blood

T2 - Critical role of xanthine oxidase and aldehyde oxidase

AU - Li, Haitao

AU - Cui, Hongmei

AU - Kundu, Tapan Kumar

AU - Alzawahra, Wael

AU - Zweier, Jay L.

PY - 2008/6/27

Y1 - 2008/6/27

N2 - Recent studies have shown that nitrite is an important storage form and source of NO in biological systems. Controversy remains, however, regarding whether NO formation from nitrite occurs primarily in tissues or in blood. Questions also remain regarding the mechanism, magnitude, and contributions of several alternative pathways of nitrite-dependent NO generation in biological systems. To characterize the mechanism and magnitude of NO generation from nitrite, electron paramagnetic resonance spectroscopy, chemiluminescence NO analyzer, and immunoassays of cGMP formation were performed. The addition of nitrite triggered a large amount of NO generation in tissues such as heart and liver, but only trace NO production in blood. Carbon monoxide increased NO release from blood, suggesting that hemoglobin acts to scavenge NO not to generate it. Administration of the xanthine oxidase (XO) inhibitor oxypurinol or aldehyde oxidase (AO) inhibitor raloxifene significantly decreased NO generation from nitrite in heart or liver. NO formation rates increased dramatically with decreasing pH or with decreased oxygen tension. Isolated enzyme studies further confirm that XO and AO, but not hemoglobin, are critical nitrite reductases. Overall, NO generation from nitrite mainly occurs in tissues not in the blood, with XO and AO playing critical roles in nitrite reduction, and this process is regulated by pH, oxygen tension, nitrite, and reducing substrate concentrations.

AB - Recent studies have shown that nitrite is an important storage form and source of NO in biological systems. Controversy remains, however, regarding whether NO formation from nitrite occurs primarily in tissues or in blood. Questions also remain regarding the mechanism, magnitude, and contributions of several alternative pathways of nitrite-dependent NO generation in biological systems. To characterize the mechanism and magnitude of NO generation from nitrite, electron paramagnetic resonance spectroscopy, chemiluminescence NO analyzer, and immunoassays of cGMP formation were performed. The addition of nitrite triggered a large amount of NO generation in tissues such as heart and liver, but only trace NO production in blood. Carbon monoxide increased NO release from blood, suggesting that hemoglobin acts to scavenge NO not to generate it. Administration of the xanthine oxidase (XO) inhibitor oxypurinol or aldehyde oxidase (AO) inhibitor raloxifene significantly decreased NO generation from nitrite in heart or liver. NO formation rates increased dramatically with decreasing pH or with decreased oxygen tension. Isolated enzyme studies further confirm that XO and AO, but not hemoglobin, are critical nitrite reductases. Overall, NO generation from nitrite mainly occurs in tissues not in the blood, with XO and AO playing critical roles in nitrite reduction, and this process is regulated by pH, oxygen tension, nitrite, and reducing substrate concentrations.

UR - http://www.scopus.com/inward/record.url?scp=49649118849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=49649118849&partnerID=8YFLogxK

U2 - 10.1074/jbc.M801785200

DO - 10.1074/jbc.M801785200

M3 - Article

C2 - 18424432

AN - SCOPUS:49649118849

VL - 283

SP - 17855

EP - 17863

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 26

ER -