Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions
Abstract
Xanthine oxidoreductase (XOR) catalyses the reduction of the therapeutic organic nitrate, nitroglycerin (glyceryl trinitrate, GTN), as well as inorganic nitrate and nitrite, to nitric oxide (NO) under hypoxic conditions in the presence of NADH. Generation of nitric oxide is not detectable under normoxic conditions and is inhibited by the molybdenum site-specific inhibitors, oxypurinol and (-)BOF 4272. These enzymic reactions provide a mechanism for generation of NO under hypoxic conditions where nitric oxide synthase does not function, suggesting a vasodilatory role in ischaemia.
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Xanthine oxidoreductase reduces inorganic nitrate and nitrite under low oxygen tension as occurs in ischemia.
“In addition to its role in purine catabolism and in reduction of molecular oxygen to superoxide, xanthine oxidoreductase (XOR) has been identified to reduce inorganic nitrate and nitrite under low oxygen tension as it occurs in ischemia.84 -86”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [85]
Animals do not encode a classical nitrate reductase, although bovine xanthine oxidase can reduce nitrate into nitrite.
“Eukaryotic nitrate reductase (eukNR) has been isolated from plants and fungi; animals do not encode a classical nitrate reductase, although bovine xanthine oxidase (XO) can reduce nitrate into nitrite.”
From Nitrate and periplasmic nitrate reductases (2014) · cites this paper as [78]
Xanthine oxidoreductase can mediate the one-electron reduction of nitrite to NO under anoxic conditions.
“Despite early studies by Zhang et al [21, 22] and Millar et al [23] demonstrating that xanthine oxidoreductse can mediate the one-electron reduction of nitrite to NO under anoxic conditions”
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 [23]
Xanthine or hypoxanthine was found to inhibit XO-catalyzed nitrite reduction.
“Moreover, xanthine or hypoxanthine was found to inhibit this reaction [101].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [101]
Xanthine oxidase may catalytically reduce nitrite back to NO under several circumstances.
“However, XO may also catalytically reduce nitrite back to NO under several circumstances [90, 100, 101].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [101]
NADH can act as an electron donor to XO to catalyze nitrite reduction.
“Different groups have shown that NADH can act as an electron donor to XO to catalyze nitrite reduction [90, 101].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [101]
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- Authors
- Millar, T. M., Stevens, C. R., Benjamin, N., Eisenthal, R., Harrison, R., & Blake, D. R.
- Affiliations
- University of Bath (GB)
- St Bartholomew's Hospital (GB)
- Corresponding author
- Stevens, Cliff R
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1998-05-08
- Volume
- 427
- Issue
- 2
- Pages
- 225-228
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W1997469875
- Cited by
- 491
- References
- 34
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 17 · 2023: 13 · 2022: 7 · 2021: 22 · 2020: 16 · 2019: 20 · 2018: 17 · 2017: 14 · 2016: 17 · 2015: 19 · 2014: 16 · 2013: 27 · 2012: 22
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- University of Warwick
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- xanthine oxidoreductase, nitric oxide production, nitrate reduction, nitrite reduction, hypoxia, oxypurinol, NADH, nitroglycerin, ischemia, vasodilation
- MeSH terms
- Animals, Cattle, Enzyme Inhibitors, Nitroglycerin, Kinetics, NAD, Nitrates, Nitric Oxide, Oxygen, Oxypurinol, Sodium Nitrite, Triazines, Xanthine Oxidase
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