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Characterization of the Magnitude and Mechanism of Aldehyde Oxidase-mediated Nitric Oxide Production from Nitrite
Open accessAbstract
Aldehyde oxidase (AO) is a cytosolic enzyme with an important role in drug and xenobiotic metabolism. Although AO has structural similarity to bacterial nitrite reductases, it is unknown whether AO-catalyzed nitrite reduction can be an important source of NO. The mechanism, magnitude, and quantitative importance of AO-mediated nitrite reduction in tissues have not been reported. To investigate this pathway and its quantitative importance, EPR spectroscopy, chemiluminescence NO analyzer, and immunoassays of cGMP formation were performed. The kinetics and magnitude of AO-dependent NO formation were characterized. In the presence of typical aldehyde substrates or NADH, AO reduced nitrite to NO. Kinetics of AO-catalyzed nitrite reduction followed Michaelis-Menten kinetics under anaerobic conditions. Under physiological conditions, nitrite levels are far below its measured K(m) value in the presence of either the flavin site electron donor NADH or molybdenum site aldehyde electron donors. Under aerobic conditions with the FAD site-binding substrate, NADH, AO-mediated NO production was largely maintained, although with aldehyde substrates oxygen-dependent inhibition was seen. Oxygen tension, substrate, and pH levels were important regulators of AO-catalyzed NO generation. From kinetic data, it was determined that during ischemia hepatic, pulmonary, or myocardial AO and nitrite levels were sufficient to result in NO generation comparable to or exceeding maximal production by constitutive NO synthases. Thus, AO-catalyzed nitrite reduction can be an important source of NO generation, and its NO production will be further increased by therapeutic administration of nitrite.
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In the citing paper
“The mechanism of nitrite reduction by AO is similar to that of XOR where nitrite is reduced at the molybdenum site and either an aldehyde can supply electrons at that same site, or NADH can supply electrons from the flavin site [93].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [93]
In the citing paper
“Again, the low Km of AO for nitrite (about 3 mM) limits its NO production rate, but it has been estimated that AO mediated NO production from nitrite can reach 1.5 nM/s at low pH in the heart [93].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [93]
In the citing paper
“Since AO has a higher affinity for NADH than XOR, it is more likely to contribute to aerobic nitrite reduction than XOR with physiological levels of NADH [93].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [93]
In the citing paper
“Under aerobic conditions, the NADH-dependent process is favored as oxygen acts as a competitive inhibitor of nitrite reduction in the absence of NADH [93].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [93]
In the citing paper
“Like other nitrite reduction pathways, lowering pH increases the rate of AO-mediated reduction, but not as much as other pathways; about 35% in going from pH 7.4 to pH 6.0 [93].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [93]
In the citing paper
“Nitrite reduction is not exclusive to hemoglobin and myoglobin, with a variety of heme-containing and non-heme containing proteins including xanthine oxidoreductase [21, 22], aldehyde oxidase [62], neuroglobin [63, 64], eNOS [65], cytochrome c [47], carbonic anhydrase [66], cytochrome c oxidase [67], complex III [68], and cytochrome P450 [69] being suggested as mediators of NO-formation.”
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 [62]
Citations
Cites
Nitric oxide: physiology, pathophysiology, and pharmacology.
Moncada, S., Palmer, R. M., & Higgs, E. A. (1991) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06663-3 · Cited by 15,525
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., & Freeman, B. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.4.1620 · Cited by 7,029
Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes
Esterbauer, H., Schaur, R. J., & Zollner, H. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90192-6 · Cited by 6,672
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9265 · Cited by 5,074
Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase
Bredt, D. S., Hwang, P. M., Glatt, C. E., Lowenstein, C. J., Reed, R. R., & Snyder, S. H. (1991) · Nature · doi:10.1038/351714a0 · Cited by 2,354
Endothelium‐derived relaxing and contracting factors
Furchgott, R. F., & Vanhoutte, P. M. (1989) · The FASEB Journal · doi:10.1096/fasebj.3.9.2545495 · Cited by 2,007
Nitric oxide, a novel neuronal messenger
Bredt, D. S., & Snyder, S. H. (1992) · Neuron · doi:10.1016/0896-6273(92)90104-l · Cited by 1,852
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807
Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate
Marletta, M. A., Yoon, P. S., Iyengar, R., Leaf, C. D., & Wishnok, J. S. (1988) · Biochemistry · doi:10.1021/bi00424a003 · Cited by 1,601
Research works printed but not linked: 1
- Sarnesto, 1996, Lab. Invest., 74, 48
Cited by
Sorted by citations
The mononuclear molybdenum enzymes
Hille, R., Hall, J., & Basu, P. (2014) · Chemical Reviews · doi:10.1021/cr400443z · Cited by 1,738
Nitric oxide signalling in cardiovascular health and disease
Farah, C., Michel, L. Y. M., & Balligand, J.-L. (2018) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.224 · Cited by 779
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Understanding nitrate assimilation and its regulation in microalgae
Sanz‐Luque, E., Chamizo‐Ampudia, A., Llamas, Á., Galván, A., & Fernández, E. M. (2015) · Frontiers in Plant Science · doi:10.3389/fpls.2015.00899 · Cited by 453
Nitrate Reductase Regulates Plant Nitric Oxide Homeostasis
Chamizo‐Ampudia, A., Sanz‐Luque, E., Llamas, Á., Galván, A., & Fernández, E. M. (2017) · Trends in Plant Science · doi:10.1016/j.tplants.2016.12.001 · Cited by 441
Metadata
- Authors
- Li, H., Kundu, T. K., & Zweier, J. L.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Li, Haitao
- Zweier, Jay L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 284
- Issue
- 49
- Pages
- 33850-33858
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2797155
- OpenAlex
- W2056934771
- Cited by
- 126
- References
- 49
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 8 · 2018: 13 · 2017: 9 · 2016: 7 · 2015: 13 · 2014: 15 · 2013: 12 · 2012: 9
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-38324, R01HL063744, HL 65608, P01HL065608, HL 63744, R01HL038324)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- aldehyde oxidase, nitric oxide production, nitrite reduction, nitrite, enzyme kinetics, Michaelis-Menten kinetics, NADH, oxygen inhibition, cyclic GMP, ischemia, nitrite therapy, nitrite reductase
- MeSH terms
- Animals, Electron Spin Resonance Spectroscopy, Flavins, Hydrogen-Ion Concentration, Immunoassay, Kinetics, Liver, Male, Molybdenum, Nitric Oxide, Nitrites, Xenobiotics, Rats, Sprague-Dawley, Aldehyde Oxidase, Rats
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