Generation of Nitric Oxide by a Nitrite Reductase Activity of Xanthine Oxidase: A Potential Pathway for Nitric Oxide Formation in the Absence of Nitric Oxide Synthase Activity

Nitric oxide (NO) synthesis is now well-known to result from the oxidation of L-arginine by a family of NO synthases (NOS). However, under hypoxic conditions this mechanism of NO synthesis may be impaired and NO is formed by a NOS independent mechanism. This study was designed to examine the reducti...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-08, Vol.249 (3), p.767-772
Main Authors: Zhang, Zhi, Naughton, Declan, Winyard, Paul G., Benjamin, Nigel, Blake, David R., Symons, Martyn C.R.
Format: Article
Language:English
Subjects:
Anaerobiosis
Animals
Cattle
Enzyme Inhibitors - pharmacology
Flavin-Adenine Dinucleotide - chemistry
Flavin-Adenine Dinucleotide - metabolism
Heparin - metabolism
Humans
In Vitro Techniques
Molybdenum - chemistry
Molybdenum - metabolism
Nitric Oxide - biosynthesis
Nitric Oxide Synthase - metabolism
Nitrite Reductases - chemistry
Nitrite Reductases - metabolism
Nitrites - metabolism
Oxidation-Reduction
Oxygen - metabolism
Substrate Specificity
Synovial Membrane - metabolism
Xanthine Oxidase - antagonists & inhibitors
Xanthine Oxidase - chemistry
Xanthine Oxidase - metabolism
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Summary:Nitric oxide (NO) synthesis is now well-known to result from the oxidation of L-arginine by a family of NO synthases (NOS). However, under hypoxic conditions this mechanism of NO synthesis may be impaired and NO is formed by a NOS independent mechanism. This study was designed to examine the reduction of nitrite to NO by xanthine oxidase (XO) under hypoxia, because the bacterial nitrate/nitrite reductases have structural similarity to XO. We found that both purified and tissue containing XO catalyze the reduction of nitrite to NO, as demonstrated using a chemiluminescent NO meter. This redox reaction requires NADH as an electron donor, and is oxygen independent. The inhibitory profiles suggest that reduction of nitrite takes place at the molybdenum center of XO whilst NADH is oxidized at the FAD center. Heparin binding of XO caused an increase in the catalysis of nitrite reduction. The XO-catalyzed generation of NO may be important in redistribution of blood flow to ischaemic tissue as a supplement to NOS, since both nitrite and NADH have been shown to be elevated in hypoxic tissue.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1998.9226