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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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.
“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]
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.
“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]
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.
“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]
Under aerobic conditions, the NADH-dependent process of AO is favored as oxygen acts as a competitive inhibitor of nitrite reduction in the absence of NADH.
“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]
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.
“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]
Nitrite reduction is not exclusive to hemoglobin and myoglobin; a variety of heme-containing and non-heme containing proteins have been suggested as mediators of NO formation.
“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]
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Enzyme-independent formation of nitric oxide in biological tissues
Zweier, J. L., Wang, P., Samouilov, A., & Kuppusamy, P. (1995) · Nature Medicine · doi:10.1038/nm0895-804 · Cited by 788 · see citing works
Webb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., & Ahluwalia, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402927101 · Cited by 608 · see citing works
Shiva, S., Huang, Z., Grubina, R., Sun, J., Ringwood, L. A., MacArthur, P. H., Xu, X., Murphy, E., Darley-Usmar, V. M., & Gladwin, M. T. (2007) · Circulation Research · doi:10.1161/01.res.0000260171.52224.6b · Cited by 599 · see citing works
Measurement of Nitric Oxide and Peroxynitrite Generation in the Postischemic Heart
Wang, P., & Zweier, J. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.46.29223 · Cited by 538 · see citing works
Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control
Huang, Z. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24650 · Cited by 520 · see citing works
Millar, T. M., Stevens, C. R., Benjamin, N., Eisenthal, R., Harrison, R., & Blake, D. R. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00430-x · Cited by 491 · see citing works
Nitrite as Regulator of Hypoxic Signaling in Mammalian Physiology
van Faassen, E. E., Bahrami, S., Feelisch, M., Hogg, N., Kelm, M., Kim‐Shapiro, D. B., Kozlov, A. V., Li, H., Lundberg, J. O., Mason, R., et al. (2009) · Medicinal Research Reviews · doi:10.1002/med.20151 · Cited by 435 · see citing works
Non-Enzymatic Nitric Oxide Synthesis in Biological Systems
Zweier, J. L., Samouilov, A., & Kuppusamy, P. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00018-3 · Cited by 363 · see citing works
A comparison of the specificities of xanthine oxidase and aldehyde oxidase
Krenitsky, T. A., Neil, S. M., Elion, G. B., & Hitchings, G. H. (1972) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(72)90078-1 · Cited by 341 · see citing works
Characterization of the Magnitude and Kinetics of Xanthine Oxidase-catalyzed Nitrite Reduction
Li, H., Samouilov, A., Liu, X., & Zweier, J. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011648200 · Cited by 280 · see citing works
Self-citationNitric Oxide Production from Nitrite Occurs Primarily in Tissues Not in the Blood
Li, H., Cui, H., Kundu, T. K., Alzawahra, W., & Zweier, J. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801785200 · Cited by 269 · see citing works
Zhang, Z., Naughton, D., Winyard, P. G., Benjamin, N., Blake, D. R., & Symons, M. C. R. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9226 · Cited by 246 · see citing works
Zweier, J. L., Wang, P., & Kuppusamy, P. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.1.304 · Cited by 244 · see citing works
Substrate Control of Free Radical Generation from Xanthine Oxidase in the Postischemic Heart
Xia, Y., & Zweier, J. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18797 · Cited by 229 · see citing works
Sodium N‐Methyl‐D‐glucamine Dithiocarbamate and Cadmium Intoxication
Shinobu, L. A., Jones, S. G., & Jones, M. M. (1984) · Acta Pharmacologica et Toxicologica · doi:10.1111/j.1600-0773.1984.tb01916.x · Cited by 221 · see citing works
Tischler, M. E., Friedrichs, D., Coll, K. E., & WILLIAMSON, J. R. (1977) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(77)90346-0 · Cited by 209 · see citing works
Lancaster, J. R., Langrehr, J. M., Bergonia, H. A., Murase, N., Simmons, R. L., & Hoffman, R. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49865-7 · Cited by 193 · see citing works
Li, H., Samouilov, A., Liu, X., & Zweier, J. L. (2003) · Biochemistry · doi:10.1021/bi026385a · Cited by 180 · see citing works
Evaluation of the Magnitude and Rate of Nitric Oxide Production from Nitrite in Biological Systems
Samouilov, A., Kuppusamy, P., & Zweier, J. L. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1998.0785 · Cited by 171 · see citing works
Ignarro, L. J., Byrns, R. E., & Wood, K. S. (1987) · Circulation Research · doi:10.1161/01.res.60.1.82 · Cited by 156 · see citing works
WILLIAMSON, J. R., & Corkey, B. E. (1979) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(79)55025-3 · Cited by 153 · see citing works
Characterization of the effects of oxygen on xanthine oxidase-mediated nitric oxide formation
Li, H., Samouilov, A., Liu, X., & Zweier, J. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314336200 · Cited by 146 · see citing works
Baker, J. E., Su, J., Fu, X., Hsu, A., Gross, G. J., Tweddell, J. S., & Hogg, N. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.07.057 · Cited by 137 · see citing works
3 Molybdenum Hydroxylases: Biological Distribution and Substrate-Inhibitor Specificity
Beedham, C. (1987) · Progress in medicinal chemistry · doi:10.1016/s0079-6468(08)70420-x · Cited by 129 · see citing works
Development of Chemiluminescence-Based Methods for Specific Quantitation of Nitrosylated Thiols
Samouilov, A., & Zweier, J. L. (1998) · Analytical Biochemistry · doi:10.1006/abio.1998.2609 · Cited by 127 · see citing works
THE DETERMINATION OF HIGHER FATTY ALDEHYDES IN TISSUES
Wittenberg, J. B., Korey, S. R., & Swenson, F. H. (1956) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65766-7 · Cited by 122 · see citing works
Organ distribution and molecular forms of human xanthine dehydrogenase/xanthine oxidase protein.
Sarnesto, A., Linder, N., & Raivio, K. O. (1996) · PubMed · Cited by 114 · see citing works
Purification, cDNA cloning, and tissue distribution of bovine liver aldehyde oxidase
Li-Calzi, M., Raviolo, C., Ghibaudi, E., De Gioia, L., Salmona, M., Cazzaniga, G., Kurosaki, M., Terao, M., & Garattini, E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.52.31037 · Cited by 107 · see citing works
Mira, L., Maia, L. B., Barreira, L. A., & Manso, C. (1995) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1995.1203 · Cited by 102 · see citing works
Wright, R. M., Vaitaitis, G. M., Wilson, C., Repine, T. B., Terada, L. S., & Repine, J. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10690 · Cited by 89 · see citing works
Kundu, T. K., Hille, R., Velayutham, M., & Zweier, J. L. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.12.032 · Cited by 83 · see citing works
Self-citationLi, H., Cui, H., Liu, X., & Zweier, J. L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411905200 · Cited by 64 · see citing works
Moriwaki, Y., Yamamoto, T., Yamaguchi, K., Takahashi, S., & Higashino, K. (1996) · Histochemistry and Cell Biology · doi:10.1007/bf01450880 · Cited by 62 · see citing works
Guinea pig liver aldehyde oxidase as a sulfoxide reductase: Its purification and characterization
Yoshihara, S., & Tatsumi, K. (1985) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(85)90495-3 · Cited by 57 · see citing works
Serum malondialdehyde-like material (MDA-LM) in acute myocardial infarction.
Aznar, J. A., Santos, M. T., Vallés, J., & Sala, J. C. (1983) · Journal of Clinical Pathology · doi:10.1136/jcp.36.6.712 · Cited by 49 · see citing works
Hemoglobin as a Nitrite Reductase Regulating Red Cell–Dependent Hypoxic Vasodilation
Gladwin, M. T. (2005) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.f294 · Cited by 42 · see citing works
An Improved Assay for Measurement of Nitric Oxide Synthase Activity in Biological Tissues
Giraldez, R. R., & Zweier, J. L. (1998) · Analytical Biochemistry · doi:10.1006/abio.1998.2721 · Cited by 32 · see citing works
Tissue distribution of the molybdenum hydroxylases, aldehyde
Beedham, C., Bruce, S. E., & Rance, D. J. (1987) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/bf03189918 · Cited by 26 · see citing works
Ando, H., Hirohiko, A. B. E., & Hisanou, R. (1993) · Clinical Cardiology · doi:10.1002/clc.4960160514 · Cited by 22 · see citing works
Flagged first, then by citations
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Sorted by citations
The mononuclear molybdenum enzymes
Hille, R., Hall, J., & Basu, P. (2014) · Chemical Reviews · doi:10.1021/cr400443z · Cited by 1,738 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Maia, L. B., & Moura, J. J. G. (2014) · Chemical Reviews · doi:10.1021/cr400518y · Cited by 401 · see citing works
Kapil, V., Khambata, R. S., Jones, D. A., Rathod, K., Primus, C., Massimo, G., Fukuto, J. M., & Ahluwalia, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019240 · Cited by 248 · see citing works
Acute effect of a high nitrate diet on brain perfusion in older adults
Presley, T. D., Morgan, A. R., Bechtold, E., Clodfelter, W., Dove, R. W., Jennings, J. M., Kraft, R. A., Bruce King, S., Laurienti, P. J., Jack Rejeski, W., et al. (2011) · Nitric Oxide · doi:10.1016/j.niox.2010.10.002 · Cited by 238 · see citing works
Medinets, S., Skiba, U., Rennenberg, H., & Butterbach‐Bahl, K. (2014) · Soil Biology and Biochemistry · doi:10.1016/j.soilbio.2014.09.025 · Cited by 219 · see citing works
Nitrite: A physiological store of nitric oxide and modulator of mitochondrial function
Shiva, S. (2013) · Redox Biology · doi:10.1016/j.redox.2012.11.005 · Cited by 207 · see citing works
“While the exact reaction scheme underlying XOR-mediated NO2 reduction is unclear, it is known that this reaction occurs at the molybdenum cofactor of XOR and aldehyde oxidase [11,12].”
BackgroundSparacino-Watkins, C. E., Tejero, J., Sun, B., Gauthier, M. C., Thomas, J., Ragireddy, V., Merchant, B. A., Wang, J., Azarov, I., Basu, P., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.555177 · Cited by 169 · see citing works
Chamizo‐Ampudia, A., Sanz‐Luque, E., Llamas, Á., Ocaña‐Calahorro, F. J., Mariscal, V., Carreras, A., Barroso, J. B., Galván, A., & Fernández, E. M. (2016) · Plant Cell & Environment · doi:10.1111/pce.12739 · Cited by 159 · see citing works
Mechanisms of nitrite bioactivation
Kim-Shapiro, D. B., & Gladwin, M. T. (2014) · Nitric Oxide · doi:10.1016/j.niox.2013.11.002 · Cited by 157 · see citing works
Nitrite and nitrate chemical biology and signalling
DeMartino, A. W., Kim‐Shapiro, D. B., Patel, R. P., & Gladwin, M. T. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14484 · Cited by 156 · see citing works
Hemoglobin-mediated nitric oxide signaling
Helms, C., & Kim-Shapiro, D. B. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.04.028 · Cited by 146 · see citing works
Cantú‐Medellín, N., & Kelley, E. E. (2013) · Nitric Oxide · doi:10.1016/j.niox.2013.02.081 · Cited by 148 · see citing works
Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits
Machha, A., & Schechter, A. N. (2011) · European Journal of Nutrition · doi:10.1007/s00394-011-0192-5 · Cited by 146 · see citing works
Li, H., Hemann, C., Abdelghany, T. M., El-Mahdy, M. A., & Zweier, J. L. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.342378 · Cited by 132 · see citing works
Self-citationThe Key Role of Nitric Oxide in Hypoxia: Hypoxic Vasodilation and Energy Supply–Demand Matching
Umbrello, M., Dyson, A., Feelisch, M., & Singer, M. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4979 · Cited by 131 · see citing works
Nitric oxide and its derivatives in the cancer battlefield
Kamm, A., Przychodzen, P., Kuban-Jankowska, A., Jacewicz, D., Dabrowska, A. M., Nussberger, S., Wozniak, M., & Gorska-Ponikowska, M. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.09.005 · Cited by 120 · see citing works
Increasing recognition of the importance of aldehyde oxidase in drug development and discovery
Garattini, E., & Terao, M. (2011) · Drug Metabolism Reviews · doi:10.3109/03602532.2011.560606 · Cited by 111 · see citing works
Skeletal muscle as an endogenous nitrate reservoir
Piknova, B., Park, J. W., Swanson, K. M., Dey, S., Noguchi, C. T., & Schechter, A. N. (2015) · Nitric Oxide · doi:10.1016/j.niox.2015.02.145 · Cited by 108 · see citing works
A comparison of organic and inorganic nitrates/nitrites
Omar, S. A., Artime, E., & Webb, A. J. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.03.008 · Cited by 106 · see citing works
Zuckerbraun, B. S., George, M. P., & Gladwin, M. T. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq370 · Cited by 97 · see citing works
Kundu, T. K., Velayutham, M., & Zweier, J. L. (2012) · Biochemistry · doi:10.1021/bi3000879 · Cited by 93 · see citing works
Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy
Zhang, Y., Janssens, S. P., Wingler, K., Schmidt, H. H. H. W., & Moens, A. L. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01315.2010 · Cited by 96 · see citing works
Aldehyde oxidase and its role as a drug metabolizing enzyme
Dalvie, D., & Di, L. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.05.011 · Cited by 90 · see citing works
Nitrite reduction by molybdoenzymes: a new class of nitric oxide-forming nitrite reductases
Maia, L. B., & Moura, J. J. G. (2015) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-014-1234-2 · Cited by 86 · see citing works
Wang, J., Krizowski, S., Fischer-Schrader, K., Niks, D., Tejero, J., Sparacino-Watkins, C., Wang, L., Ragireddy, V., Frizzell, S., Kelley, E. E., et al. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5397 · Cited by 84 · see citing works
The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation
Duchemin, S., Boily, M., Sadekova, N., & Girouard, H. (2012) · Frontiers in Neural Circuits · doi:10.3389/fncir.2012.00051 · Cited by 83 · see citing works
Molybdenum as an Essential Element for Crops: An Overview
Hu, C. (2020) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2020.24.004104 · Cited by 82 · see citing works
A new paradigm for XOR-catalyzed reactive species generation in the endothelium
Kelley, E. E. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2015.05.004 · Cited by 78 · see citing works
Castiglione, N., Rinaldo, S., Giardina, G., Stelitano, V., & Cutruzzolà, F. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4196 · Cited by 79 · see citing works
Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite reductases
Maia, L. B., & Moura, J. J. G. (2011) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-010-0741-z · Cited by 75 · see citing works
Nitrite‐dependent nitric oxide synthesis by molybdenum enzymes
Bender, D. A., & Schwarz, G. (2018) · FEBS Letters · doi:10.1002/1873-3468.13089 · Cited by 73 · see citing works
Lee, J.-O., Choi, E., Shin, K. K., Hong, Y. H., Kim, H. G., Jeong, D., Hossain, M. A., Kim, H. S., Yi, Y., Kim, D., et al. (2018) · Journal of Ginseng Research · doi:10.1016/j.jgr.2018.10.003 · Cited by 72 · see citing works
The potential role of the red blood cell in nitrite-dependent regulation of blood flow
Patel, R. P., Hogg, N., & Kim-Shapiro, D. B. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq323 · Cited by 70 · see citing works
Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation
Waltz, P., Escobar, D., Botero, A. M., & Zuckerbraun, B. S. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6256 · Cited by 70 · see citing works
Bueno, M., Wang, J., Mora, A. L., & Gladwin, M. T. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4833 · Cited by 68 · see citing works
Fu, C., Di, L., Han, X., Soderstrom, C., Snyder, M., Troutman, M. D., Obach, R. S., & Zhang, H. (2013) · Drug Metabolism and Disposition · doi:10.1124/dmd.113.053082 · Cited by 66 · see citing works
Maia, L. B., Pereira, V., Mira, L., & Moura, J. J. G. (2014) · Biochemistry · doi:10.1021/bi500987w · Cited by 62 · see citing works
Mechanisms impairing blood pressure responses to nitrite and nitrate
Oliveira‐Paula, G. H., Pinheiro, L. C., & Tanus-Santos, J. E. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.01.015 · Cited by 60 · see citing works
Vitturi, D. A., & Patel, R. P. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.037 · Cited by 59 · see citing works
Protein tyrosine nitration in cellular signal transduction pathways
Yakovlev, V. A., & Mikkelsen, R. B. (2010) · Journal of Receptors and Signal Transduction · doi:10.3109/10799893.2010.513991 · Cited by 58 · see citing works
A NO way to BOLD?: Dietary nitrate alters the hemodynamic response to visual stimulation
Aamand, R., Dalsgaard, T., Ho, Y.-C. L., Møller, A., Roepstorff, A., & Lund, T. E. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.06.069 · Cited by 55 · see citing works
Maia, L. B., & Moura, J. J. G. (2018) · Redox Biology · doi:10.1016/j.redox.2018.08.020 · Cited by 56 · see citing works
Involvement of NR and PM-NR in NO biosynthesis in cucumber plants subjected to salt stress
Reda, M., Golicka, A., Kabała, K., & Janicka, M. (2017) · Plant Science · doi:10.1016/j.plantsci.2017.11.004 · Cited by 54 · see citing works
Nitrogen oxide cycle regulates nitric oxide levels and bacterial cell signaling
Sasaki, Y., Oguchi, H., Kobayashi, T., Kusama, S., Sugiura, R., Moriya, K., Hirata, T., Yukioka, Y., Takaya, N., Yajima, S., et al. (2016) · Scientific Reports · doi:10.1038/srep22038 · Cited by 51 · see citing works
Rix, P. J., Vick, A., Attkins, N., Barker, G. E., Bott, A. W., Alcorn, H. W., Gladwin, M. T., Shiva, S., Bradley, S. P., Hussaini, A., et al. (2014) · Clinical Pharmacokinetics · doi:10.1007/s40262-014-0201-y · Cited by 48 · see citing works
Nitric oxide pathology and therapeutics in sickle cell disease
Kim‐Shapiro, D. B., & Gladwin, M. T. (2018) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-189009 · Cited by 47 · see citing works
Pattillo, C. B., Bir, S. C., Rajaram, V., & Kevil, C. G. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq297 · Cited by 43 · see citing works
Nitrocobinamide, a New Cyanide Antidote That Can Be Administered by Intramuscular Injection
Chan, A., Jiang, J., Fridman, A., Guo, L. T., Shelton, G. D., Liu, M., Green, C., Haushalter, K. J., Patel, H. H., Lee, J., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501565k · Cited by 43 · see citing works
The role of nitrite in neurovascular coupling
Piknova, B., Kocharyan, A., Schechter, A. N., & Silva, A. C. (2011) · Brain Research · doi:10.1016/j.brainres.2011.06.045 · Cited by 40 · see citing works
The role of nitrogen metabolism on polyethylene biodegradation
Peixoto, J., Vizzotto, C. S., Ramos, A., Alves, G. S. C., Steindorff, A. S., & Krüger, R. H. (2022) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2022.128682 · Cited by 38 · see citing works
Mechanisms of the protective effects of nitrate and nitrite in cardiovascular and metabolic diseases
Liu, Y., Croft, K. D., Hodgson, J. M., Mori, T., & Ward, N. C. (2020) · Nitric Oxide · doi:10.1016/j.niox.2020.01.006 · Cited by 41 · see citing works
Time Course of Aldehyde Oxidase and Why It Is Nonlinear
Abbasi, A., Paragas, E. M., Joswig-Jones, C. A., Rodgers, J. T., & Jones, J. P. (2019) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.085787 · Cited by 37 · see citing works
Blood, A. B., Schroeder, H. J., Terry, M. H., Merrill-Henry, J., Bragg, S. L., Vrancken, K., Liu, T., Herring, J. L., Sowers, L. C., Wilson, S. M., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.001073 · Cited by 36 · see citing works
Weidert, E. R., Schoenborn, S. O., Cantú‐Medellín, N., Choughule, K. V., Jones, J. P., & Kelley, E. E. (2014) · Nitric Oxide · doi:10.1016/j.niox.2013.12.010 · Cited by 36 · see citing works
Barr, J., Jones, J. P., Joswig-Jones, C. A., & Rock, D. A. (2013) · Molecular Pharmaceutics · doi:10.1021/mp4003046 · Cited by 36 · see citing works
Lai, Y., Pan, K., Chang, G., Hsu, C.-H., Khoo, K., Hung, C., Jiang, Y., Ho, F., & Meng, T. (2011) · Circulation Research · doi:10.1161/circresaha.111.256479 · Cited by 35 · see citing works
Rendić, S., Crouch, R. D., & Guengerich, F. P. (2022) · Archives of Toxicology · doi:10.1007/s00204-022-03304-3 · Cited by 34 · see citing works
Nitrite-stimulated Gastric Formation of S-nitrosothiols As An Antihypertensive Therapeutic Strategy
Oliveira‐Paula, G. H., & Tanus-Santos, J. E. (2018) · Current Drug Targets · doi:10.2174/1389450119666180816120816 · Cited by 33 · see citing works
Liu, M., Zollbrecht, C., Peleli, M., Lundberg, J. O., Weitzberg, E., & Carlström, M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.03.025 · Cited by 30 · see citing works
Sulfide and transition metals - A partnership for life
Maiti, B. K., Maia, L. B., & Moura, J. J. G. (2021) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2021.111687 · Cited by 30 · see citing works
The two faces of aldehyde oxidase: Oxidative and reductive transformations of 5-nitroquinoline
Paragas, E. M., Humphreys, S. C., Min, J., Joswig-Jones, C. A., & Jones, J. P. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.09.002 · Cited by 30 · see citing works
Involvement of secondary messengers and small organic molecules in auxin perception and signaling
Di, D., Zhang, C., & Guo, G. (2015) · Plant Cell Reports · doi:10.1007/s00299-015-1767-z · Cited by 29 · see citing works
Vanderpool, R. R., & Gladwin, M. T. (2014) · Circulation · doi:10.1161/circulationaha.114.014149 · Cited by 29 · see citing works
Carbonic anhydrase II does not exhibit Nitrite reductase or Nitrous Anhydrase Activity
Andring, J. T., Lomelino, C. L., Tu, C., Silverman, D. N., McKENNA, R. V., & Swenson, E. R. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.01.015 · Cited by 27 · see citing works
Machine Learning Models for the Prediction of Chemotherapy-Induced Peripheral Neuropathy
Bloomingdale, P., & Mager, D. E. (2019) · Pharmaceutical Research · doi:10.1007/s11095-018-2562-7 · Cited by 26 · see citing works
Mota, C., Coelho, C., Leimkühler, S., Garattini, E., Terao, M., Santos‐Silva, T., & Romão, M. J. (2018) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2018.04.006 · Cited by 26 · see citing works
Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate
Hughan, K. S., Wendell, S. G., Delmastro-Greenwood, M. M., Helbling, N. L., Corey, C. G., Bellavia, L., Potti, G. K., Grimes, G. J., Goodpaster, B. H., Kim‐Shapiro, D. B., et al. (2017) · Hypertension · doi:10.1161/hypertensionaha.117.09016 · Cited by 26 · see citing works
Kelley, E. E. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1523-8 · Cited by 28 · see citing works
Molybdenum-containing nitrite reductases: Spectroscopic characterization and redox mechanism
Wang, J., Keceli, G., Cao, R., Su, J., & Mi, Z. (2016) · Redox Report · doi:10.1080/13510002.2016.1206175 · Cited by 24 · see citing works
Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure
Coggan, A. R., & Peterson, L. R. (2016) · Current Heart Failure Reports · doi:10.1007/s11897-016-0293-9 · Cited by 20 · see citing works
Nitric oxide and nitrite-based therapeutic opportunities in intimal hyperplasia
Alef, M. J., Tzeng, E., & Zuckerbraun, B. S. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.03.014 · Cited by 20 · see citing works
Nitrite Reductases in Biomedicine: From Natural Enzymes to Artificial Mimics
Zhu, S., Liu, Z., Hu, B., Feng, Y., & Pan, G. (2025) · Research · doi:10.34133/research.0710 · Cited by 20 · see citing works
Nitric Oxide and Cerebrovascular Regulation
Tabatabaei, S. N., & Girouard, H. (2014) · Vitamins and hormones · doi:10.1016/b978-0-12-800254-4.00014-3 · Cited by 18 · see citing works
Corpas, F. J., Taboada, J., Sánchez‐Romera, B., López-Jaramillo, J., & Palma, J. M. (2025) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2025.110000 · Cited by 17 · see citing works
Maia, L. B., & Moura, J. J. G. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3600-7_8 · Cited by 17 · see citing works
Mechanism of nitrite-dependent NO synthesis by human sulfite oxidase
Bender, D. A., Kaczmarek, A. T., Niks, D., Hille, R., & Schwarz, G. (2019) · Biochemical Journal · doi:10.1042/bcj20190143 · Cited by 17 · see citing works
Enzyme Kinetics, Inhibition, and Regioselectivity of Aldehyde Oxidase
Barr, J., Choughule, K. V., & Jones, J. P. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-758-7_9 · Cited by 15 · see citing works
Carbonic anhydrase II does not regulate nitrite‐dependent nitric oxide formation and vasodilation
Wang, L., Sparacino-Watkins, C. E., Wang, J., Wajih, N., Varano, P., Xu, Q., Cecco, E., Tejero, J., Soleimani, M., Kim‐Shapiro, D. B., et al. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14887 · Cited by 14 · see citing works
Yavuz, C., Yazıcı, S., Karahan, O., Demirtaş, S., Çalışkan, A., Güçlü, O., Ertaş, F., & Mavitaş, B. (2013) · Biomarkers · doi:10.3109/1354750x.2012.745165 · Cited by 13 · see citing works
Erythrocytic bioactivation of nitrite and its potentiation by far-red light
Wajih, N., Basu, S., Ucer, K. B., Rigal, F. J., Shakya, A., Rahbar, E., Vachharajani, V., Guthold, M., Gladwin, M. T., Smith, L. M., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.11.001 · Cited by 13 · see citing works
Reciprocal regulation of sulfite oxidation and nitrite reduction by mitochondrial sulfite oxidase
Kaczmarek, A. T., Strampraad, M. J. F., Hagedoorn, P., & Schwarz, G. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.04.004 · Cited by 13 · see citing works
ecoAO: A Simple System for the Study of Human Aldehyde Oxidases Role in Drug Metabolism
Paragas, E. M., Humphreys, S. C., Min, J., Joswig-Jones, C. A., Leimkühler, S., & Jones, J. P. (2017) · ACS Omega · doi:10.1021/acsomega.7b01054 · Cited by 12 · see citing works
Indirect Antioxidant Effects of the Nitrite Anion: Focus on Xanthine Oxidase
Williams, X. M., Bossert, A. T., DeVallance, E., Lewis, S. E., Gunther, M. R., & Kelley, E. E. (2022) · Advances in Redox Research · doi:10.1016/j.arres.2022.100058 · Cited by 10 · see citing works
Breed and adaptive response modulate bovine peripheral blood cells’ transcriptome
Pošćić, N., Montanari, T., D’Andrea, M., Licastro, D., Pilla, F., Ajmone‐Marsan, P., Minuti, A., & Sgorlon, S. (2017) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-017-0143-y · Cited by 11 · see citing works
Role of nitrite in regulation of fetal cephalic circulation in sheep
Truong, G. T., Schröder, H. J., Liu, T., Zhang, M., Kanda, E., Bragg, S. L., Power, G. G., & Blood, A. B. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.269340 · Cited by 10 · see citing works
Role of xanthine oxidoreductase in the anti-thrombotic effects of nitrite in ratsin vivo
Kramkowski, K., Leszczynska, A., Przyborowski, K., Kaminski, T. W., Rykaczewska, U., Sitek, B., Zakrzewska, A., Proniewski, B., Smolenski, R. T., Chabielska, E., et al. (2015) · Platelets · doi:10.3109/09537104.2015.1083545 · Cited by 10 · see citing works
Sparacino-Watkins, C. E., & Lancaster, J. R. (2021) · Nitric Oxide · doi:10.1016/j.niox.2021.10.001 · Cited by 9 · see citing works
Nitrite-NO bailout for a NOS complex too big to fail
Gladwin, M. T., & Tejero, J. (2011) · Nature Medicine · doi:10.1038/nm.2591 · Cited by 7 · see citing works
Increased consumption and vasodilatory effect of nitrite during exercise
Hon, Y. Y., Lin, E. E., Tian, X., Yang, Y., Sun, H., Swenson, E. R., Taveira‐DaSilva, A. M., Gladwin, M. T., & Machado, R. F. (2015) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00081.2015 · Cited by 8 · see citing works
Bringing Nitric Oxide to the Molybdenum World—A Personal Perspective
Maia, L. B. (2023) · Molecules · doi:10.3390/molecules28155819 · Cited by 7 · see citing works
RAGE against the stress: Mitochondrial suppression in hypometabolic hearts
Al-attar, R., & Storey, K. B. (2020) · Gene · doi:10.1016/j.gene.2020.145039 · Cited by 7 · see citing works
Abbasi, A., Joswig-Jones, C. A., & Jones, J. P. (2020) · Drug Metabolism and Disposition · doi:10.1124/dmd.120.000187 · Cited by 7 · see citing works
Biochemistry of Molybdopterin Nitrate/Nitrite Reductases
Kelley, E. E. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804273-1.00013-2 · Cited by 7 · see citing works
Urarte, E., Esteban, R., Morán, J. F., & Bittner, F. (2014) · Signaling and communication in plants · doi:10.1007/978-3-319-10079-1_2 · Cited by 5 · see citing works
Allergic activation of mast cells.
Parker, C. W. (1986) · PubMed · Cited by 5 · see citing works
Kramkowski, K., Leszczynska, A., Przyborowski, K., Proniewski, B., Marcińczyk, N., Rykaczewska, U., Jarmoc, D., Chabielska, E., & Chłopicki, S. (2016) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-016-1308-5 · Cited by 4 · see citing works
- 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 › 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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