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Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control
Open accessAbstract
Hypoxic vasodilation is a fundamental, highly conserved physiological response that requires oxygen and/or pH sensing coupled to vasodilation. While this process was first characterized more than 80 years ago, the precise identity and mechanism of the oxygen sensor and mediators of vasodilation remain uncertain. In support of a possible role for hemoglobin (Hb) as a sensor and effector of hypoxic vasodilation, here we show biochemical evidence that Hb exhibits enzymatic behavior as a nitrite reductase, with maximal NO generation rates occurring near the oxy-to-deoxy (R-to-T) allosteric structural transition of the protein. The observed rate of nitrite reduction by Hb deviates from second-order kinetics, and sigmoidal reaction progress is determined by a balance between 2 opposing chemistries of the heme in the R (oxygenated conformation) and T (deoxygenated conformation) allosteric quaternary structures of the Hb tetramer--the greater reductive potential of deoxyheme in the R state tetramer and the number of unligated deoxyheme sites necessary for nitrite binding, which are more plentiful in the T state tetramer. These opposing chemistries result in a maximal nitrite reduction rate when Hb is 40-60% saturated with oxygen (near the Hb P50), an apparent ideal set point for hypoxia-responsive NO generation. These data suggest that the oxygen sensor for hypoxic vasodilation is determined by Hb oxygen saturation and quaternary structure and that the nitrite reductase activity of Hb generates NO gas under allosteric and pH control.
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In the citing paper
“They showed that nitrite bioactivation is most prevalent during rapid deoxygenation, reaching a maximum conversion and nitric oxide-mediated effects at 50% oxygen bound hemoglobin.73,74”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [73]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Nitrite appears to mediate the majority of its effects through bioactivation to NO.This occurs mainly via nitrite reductases, which have selective activity under oxygen/hypoxic/ischaemic conditions”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [120]
Experimental — accuracy not yet measuredIn the citing paper
“The reaction of deoxyHb with nitrite shows an increase in the instantaneous reaction rate as the reaction progresses (447). Studies with T-state and R-state Hb–stabilizing compounds have unambiguously identified the reason for this change is the shift from T-state to R-state during the course of the reaction, as the NO formed in the reaction binds to the unreacted deoxyHb to stabilize the R-state.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [447]
In the citing paper
“The rate constants for the reaction of Hb with nitrite change from 0.12 M−1s−1 for T-state Hb to 6.0 M−1s−1 for R-state Hb (Table 3) (447).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [447]
In the citing paper
“This scheme has been found to apply to virtually all the heme protein–mediated nitrite reduction reactions studied to date, including Hb (248, 447), Mb (247, 862), neuroglobin (Ngb) (932, 945), Cygb (182, 571, 780), cystathionine β-synthase (CBS) (149, 350), globin X (184), plant and cyanobacterial Hb (phytohemoglobins) (905, 946), flavohemoglobin (340), heme-albumin (43), cytochrome c (41), prot”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [447]
In the citing paper
“Nitrite metabolism can be activated by hypoxia, low pH and reactions with metalloproteins[50–58].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [53]
In the citing paper
“As with NOS-derived NO, inorganic nitrite demonstrates robust NO-signaling effects[52,53,57,59] and contributes to basal vascular tone[51,55,60,61], blood pressure[62–66], protection from endothelial dysfunction[67–71] and vascular inflammation[72] under conditions of metabolic and inflammatory stress.”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [53]
In the citing paper
“(1)NO2−+HbFe2++H+→NO+HbFe3++OH−”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [36]
In the citing paper
“Interestingly, the rate of reduction has been found to depend on the allosteric state of the protein, with vacant hemes in an R-state Hb tetramer reacting about 100 times faster than those in the T-state [36–38].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [36]
In the citing paper
“The rate of NO production is thus maximal at partial oxygen saturations near the p50 of Hb (Figure 3) [36, 38].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [36]
In the citing paper
“The maximum rate of NO production at this oxygen pressure, taking a bimolecular rate constant of 1 M−1s−1 [36], 0.01 M heme, and 100 nM nitrite would be 1 nanomolar/sec.”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [36]
In the citing paper
“This differential reactivity of nitrite reduction versus oxidation being controlled by oxygen tension (i.e. presence of deoxygenated vs oxygenated hemoglobin / myoglobin) illustrates the biochemical mechanism underlying the proposed model in which nitrite can selectively produce NO during graded hypoxia [5, 25-28].”
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 [27]
In the citing paper
“However, experiments by Cosby et al showed that intra-arterial infusion of nitrite at near-physiological levels causes vasodilation in an arterio-venous gradient manner that is influenced by R-T state conversion and oxygen tension implicating red cell reduction of nitrite to NO [19, 106, 107].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [107]
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Citations
Cites
Perutz, M. F. (1970) · Nature · doi:10.1038/228726a0 · Cited by 2,914
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
S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control
Jia, L., Bonaventura, C., Bonaventura, J., & Stamler, J. S. (1996) · Nature · doi:10.1038/380221a0 · Cited by 1,592
Arnold, W. P., Mittal, C. K., Katsuki, S., & Murad, F. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.8.3203 · Cited by 1,459
Blood Flow Regulation by S -Nitrosohemoglobin in the Physiological Oxygen Gradient
Stamler, J. S., Jia, L., Eu, J. P., McMahon, T. J., Demchenko, I. T., Bonaventura, J., Gernert, K., & Piantadosi, C. A. (1997) · Science · doi:10.1126/science.276.5321.2034 · Cited by 1,050
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
Nitrate, bacteria and human health
Lundberg, J. O., Weitzberg, E., Cole, J. A., & Benjamin, N. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro929 · Cited by 739
Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674
Furchgott, R. F., & Bhadrakom, S. (1953) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)05163-8 · Cited by 655
Oxidation of nitrogen-oxides by bound dioxygen in hemoproteins
Doyle, M. P., & Hoekstra, J. W. (1981) · Journal of Inorganic Biochemistry · doi:10.1016/s0162-0134(00)80291-3 · Cited by 643
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Grau, M., Hendgen-Cotta, U. B., Brouzos, P., Drexhage, C., Rassaf, T., Lauer, T., Dejam, A., Kelm, M., & Kleinbongard, P. (2007) · Journal of Chromatography B · doi:10.1016/j.jchromb.2007.02.002 · Cited by 100
Zuckerbraun, B. S., George, M. P., & Gladwin, M. T. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq370 · Cited by 99
Zhu, S.-G., Kukreja, R. C., Das, A., Chen, Q., Lesnefsky, E. J., & Xi, L. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.01.024 · Cited by 96
Yi, J., Heinecke, J. L., Tan, H., Ford, P. C., & Richter-Addo, G. B. (2009) · Journal of the American Chemical Society · doi:10.1021/ja904726q · Cited by 96
Ahluwalia, A., Gladwin, M., Coleman, G. D., Hord, N., Howard, G., Kim‐Shapiro, D. B., Lajous, M., Larsen, F. J., Lefer, D. J., McClure, L. A., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003402 · Cited by 92
The redox interplay between nitrite and nitric oxide: From the gut to the brain
Pereira, C., Ferreira, N. R., Rocha, B. S., Barbosa, R. M., & Laranjinha, J. (2013) · Redox Biology · doi:10.1016/j.redox.2013.04.004 · Cited by 92
Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function
Shiva, S., & Gladwin, M. T. (2009) · Basic Research in Cardiology · doi:10.1007/s00395-009-0009-3 · Cited by 91
Rate of nitric oxide scavenging by hemoglobin bound to haptoglobin
Azarov, I., He, X., Jeffers, A. B., Basu, S., Ucer, B., Hantgan, R. R., Levy, A. P., & Kim‐Shapiro, D. B. (2008) · Nitric Oxide · doi:10.1016/j.niox.2008.02.006 · Cited by 89
Chazov, E. I., Rodnenkov, O. V., Zorin, A. V., Lakomkin, V. L., Владимирович, Г. В., Выборов, О. Н., Драгнев, А. Г., Timoshin, A. A., Buryachkovskaya, L. I., Abramov, A. A., et al. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.01.008 · Cited by 89
Mitochondria as metabolizers and targets of nitrite
Shiva, S. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.09.002 · Cited by 87
McMahon, T. J., & Doctor, A. (2006) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200507-066bg · Cited by 87
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 88
Heme-based catalytic properties of human serum albumin
Ascenzi, P., di Masi, A., Fanali, G., & Fasano, M. (2015) · Cell Death Discovery · doi:10.1038/cddiscovery.2015.25 · Cited by 86
Gao, M., Wang, R., Yu, F., & Chen, L. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.01.011 · Cited by 85
Evolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell Vasculopathy
Kato, G. J. (2008) · JAMA · doi:10.1001/jama.2008.598 · Cited by 85
Dias-Junior, C. A. C., Gladwin, M. T., & Tanus-Santos, J. E. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.08.022 · Cited by 82
Heinecke, J. L., & Ford, P. C. (2009) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2009.07.021 · Cited by 82
Isbell, T. S., Gladwin, M. T., & Patel, R. P. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00759.2007 · Cited by 82
Effects of nitrite on modulating ROS generation following ischemia and reperfusion
Raat, N. J. H., Shiva, S., & Gladwin, M. T. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.02.002 · Cited by 79
Castiglione, N., Rinaldo, S., Giardina, G., Stelitano, V., & Cutruzzolà, F. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4196 · Cited by 81
Modeling heme proteins using atomistic simulations
Bikiel, D. E., Boechi, L., Capece, L., Crespo, A., Biase, P. M. D., Lella, S. D., Lebrero, M. C. G., Marti, M. A., Nadra, A. D., Perissinotti, L. L., et al. (2006) · Physical Chemistry Chemical Physics · doi:10.1039/b611741b · Cited by 78
Tejero, J., Sparacino-Watkins, C. E., Ragireddy, V., Frizzell, S. A., & Gladwin, M. T. (2015) · Biochemistry · doi:10.1021/bi501196k · Cited by 77
Hemoglobin: A Nitric-Oxide Dioxygenase
Gardner, P. R. (2012) · Scientifica · doi:10.6064/2012/683729 · Cited by 80
Liu, Z.-R., Tang, Y., Xu, A., & Lin, W. (2016) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2016.09.107 · Cited by 77
Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle
Doctor, A., & Stamler, J. S. (2011) · Comprehensive physiology · doi:10.1002/cphy.c090009 · Cited by 78
Mechanisms of Human Erythrocytic Bioactivation of Nitrite
Liu, C., Wajih, N., Liu, X., Basu, S., Janes, J., Marvel, M., Keggi, C., Helms, C. C., Lee, A. N., Belanger, A. M., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.609222 · Cited by 76
Ma, Y., Hoepker, A. C., Gupta, L., Faggin, M. F., & Collum, D. B. (2010) · Journal of the American Chemical Society · doi:10.1021/ja105855v · Cited by 75
Godenschwager, P. F., & Collum, D. B. (2008) · Journal of the American Chemical Society · doi:10.1021/ja800250q · Cited by 75
Effects of sodium nitrite on ischemia–reperfusion injury in the rat kidney
Basireddy, M., Isbell, T. S., Teng, X., Patel, R. P., & Agarwal, A. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00334.2005 · Cited by 72
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
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
Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin
Bonaventura, C., Henkens, R. W., Alayash, A. I., Banerjee, S., & Crumbliss, A. L. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4947 · Cited by 71
Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning
Azarov, I., Wang, L., Rose, J. J., Xu, Q., Huang, X. N., Belanger, A., Wang, Y., Guo, L., Liu, C., Ucer, K. B., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aah6571 · Cited by 70
Sonveaux, P., Lobysheva, I. I., Féron, O., & McMahon, T. J. (2007) · Physiology · doi:10.1152/physiol.00042.2006 · Cited by 71
Nitrite Reductase Activity of Nonsymbiotic Hemoglobins from Arabidopsis thaliana
Tiso, M., Tejero, J., Kenney, C., Frizzell, S., & Gladwin, M. T. (2012) · Biochemistry · doi:10.1021/bi300570v · Cited by 69
Nitrite and nitric oxide metabolism in peripheral artery disease
Allen, J. D., Giordano, T., & Kevil, C. G. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.03.003 · Cited by 71
Hoepker, A. C., Gupta, L., Ma, Y., Faggin, M. F., & Collum, D. B. (2011) · Journal of the American Chemical Society · doi:10.1021/ja200906z · Cited by 69
Bueno, M., Wang, J., Mora, A. L., & Gladwin, M. T. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4833 · Cited by 68
Dissecting plant iron homeostasis under short and long-term iron fluctuations
Darbani, B., Briat, J., Holm, P. B., Husted, S., Noeparvar, S., & Borg, S. (2013) · Biotechnology Advances · doi:10.1016/j.biotechadv.2013.05.003 · Cited by 68
Stapley, R. D., Owusu, B. Y., Brandon, A. P., Cusick, M. V., Rodriguez, C. A., Marques, M. B., Kerby, J. D., Barnum, S. R., Weinberg, J. A., Lancaster, J. R., et al. (2012) · Biochemical Journal · doi:10.1042/bj20120675 · Cited by 68
Shining a light on tissue NO stores: Near infrared release of NO from nitrite and nitrosylated hemes
Shiva, S., & Gladwin, M. T. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2008.10.005 · Cited by 68
Myoglobin functions in the heart
Hendgen-Cotta, U. B., Kelm, M., & Rassaf, T. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.05.005 · Cited by 67
Bizjak, D. A., Brinkmann, C. K., Bloch, W., & Grau, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125206 · Cited by 67
A Microscopic Study of the Deoxyhemoglobin-Catalyzed Generation of Nitric Oxide from Nitrite Anion
Perissinotti, L. L., Marti, M. A., Doctorovich, F. A., Luque, F. J., & Estrin, D. A. (2008) · Biochemistry · doi:10.1021/bi801104c · Cited by 67
Oh, J., Hamm, J. D., Xu, X., Genschmer, K. R., Zhong, M., Lebensburger, J. D., Marques, M. B., Kerby, J. D., Pittet, J., Gaggar, A., et al. (2016) · Redox Biology · doi:10.1016/j.redox.2016.08.003 · Cited by 66
Chirinos, J. A., & Zamani, P. L. (2016) · Current Heart Failure Reports · doi:10.1007/s11897-016-0277-9 · Cited by 66
Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II study
Mack, A. K., McGowan II, V. R., Tremonti, C. K., Ackah, D., Barnett, C., Machado, R. F., Gladwin, M. T., & Kato, G. J. (2008) · British Journal of Haematology · doi:10.1111/j.1365-2141.2008.07259.x · Cited by 64
Jensen, F. B., & Rohde, S. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00813.2009 · Cited by 63
Omar, S. A., Fok, H., Tilgner, K., Nair, A., Hunt, J., Jiang, B., Taylor, P. D., Chowienczyk, P., & Webb, A. J. (2014) · Circulation · doi:10.1161/circulationaha.114.009554 · Cited by 65
Nitric oxide from nitrite reduction by hemoglobin in the plasma and erythrocytes
Chen, K., Piknova, B., Pittman, R. N., Schechter, A. N., & Popel, A. S. (2007) · Nitric Oxide · doi:10.1016/j.niox.2007.09.088 · Cited by 65
Regulation of nitrite transport in red blood cells by hemoglobin oxygen fractional saturation
Vitturi, D. A., Teng, X., Toledo, J. C., Matalon, S., Lancaster, J. R., & Patel, R. P. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01303.2008 · Cited by 62
Rassaf, T., Ferdinandy, P., & Schulz, R. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12291 · Cited by 62
Nitrite as an intrinsic signaling molecule
Gladwin, M. T. (2005) · Nature Chemical Biology · doi:10.1038/nchembio1005-245 · Cited by 62
Maia, L. B., Pereira, V., Mira, L., & Moura, J. J. G. (2014) · Biochemistry · doi:10.1021/bi500987w · Cited by 64
Hannas, B. R., Das, P. C., Li, H., & LeBlanc, G. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012453 · Cited by 61
Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation
Bailey, J., Feelisch, M., Horowitz, J. D., Frenneaux, M. P., & Madhani, M. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.06.009 · Cited by 61
Minneci, P. C., Deans, K. J., Shiva, S., Zhi, H., Banks, S. M., Kern, S. J., Natanson, C., Solomon, S. B., & Gladwin, M. T. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00151.2008 · Cited by 62
Vitturi, D. A., & Patel, R. P. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.037 · Cited by 59
Parallel evolution of Nitric Oxide signaling: Diversity of synthesis and memory pathways
Moroz, L. L. (2011) · Frontiers in bioscience · doi:10.2741/3837 · Cited by 59
On the mechanism by which dietary nitrate improves human skeletal muscle function
Affourtit, C., Bailey, S. J., Jones, A. M., Smallwood, M. J., & Winyard, P. G. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00211 · Cited by 58
Khatri, J., Mills, C. E., Maskell, P., Odongerel, C., & Webb, A. J. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12913 · Cited by 60
Jaitovich, A., & Jourd’heuil, D. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-63245-2_6 · Cited by 59
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Flögel, U., Fago, A., & Rassaf, T. (2010) · Journal of Experimental Biology · doi:10.1242/jeb.041681 · Cited by 57
Vascular Effects of the Red Blood Cell Storage Lesion
Roback, J. D. (2011) · Hematology · doi:10.1182/asheducation-2011.1.475 · Cited by 57
Helbo, S., Dewilde, S., Williams, D. R., Berghmans, H., Berenbrink, M., Cossins, A. R., & Fago, A. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00501.2011 · Cited by 57
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Totzeck, M., Hendgen-Cotta, U. B., & Rassaf, T. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-55330-6_18 · Cited by 57
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Totzeck, M., Hendgen-Cotta, U. B., Rammos, C., Frommke, L.-M., Knackstedt, C., Predel, H.-G., Kelm, M., & Rassaf, T. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.05.003 · Cited by 56
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Mills, C. E., Khatri, J., Maskell, P., Odongerel, C., & Webb, A. J. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12918 · Cited by 57
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Rifkind, J. M., Nagababu, E., Barbiro‐Michaely, E., Ramasamy, S., Pluta, R. M., & Mayevsky, A. (2007) · Nitric Oxide · doi:10.1016/j.niox.2007.04.002 · Cited by 56
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Pedersen, C. L., Faggiano, S., Helbo, S., Gesser, H., & Fago, A. (2010) · Journal of Experimental Biology · doi:10.1242/jeb.041624 · Cited by 52
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Zhai, B., Hu, W., Sun, J., Chi, S., Lei, Y., Zhang, F., Zhong, C., & Liu, Z. (2017) · The Analyst · doi:10.1039/c7an00058h · Cited by 50
Санина, Н. А., Syrtsova, L. A., Shkondina, N. I., Руднева, Т. Н., Malkova, E. S., Bazanov, T. A., Kotelnikov, A. I., & Aldoshin, S. M. (2006) · Nitric Oxide · doi:10.1016/j.niox.2006.10.005 · Cited by 50
Frérart, F., Sonveaux, P., Rath, G., Smoos, A., Meqor, A., Charlier, N., Jordan, B. F., Saliez, J., Noël, A., Dessy, C., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4001 · Cited by 49
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Rosa, M. C. D., Alinovi, C. C., Galtieri, A., Scatena, R., & Giardina, B. (2007) · Gene · doi:10.1016/j.gene.2007.02.048 · Cited by 48
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Metadata
- Authors
- Huang, Z.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Huang, Z.
- ORCID
- Huang, Z.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-08-01
- Volume
- 115
- Issue
- 8
- Pages
- 2099-2107
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1177999
- OpenAlex
- W2120714892
- Cited by
- 520
- References
- 57
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 16 · 2023: 18 · 2022: 9 · 2021: 11 · 2020: 17 · 2019: 19 · 2018: 21 · 2017: 20 · 2016: 25 · 2015: 29 · 2014: 33 · 2013: 41 · 2012: 40
- FWCI
- 13.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- North Carolina Biotechnology Center
- National Institutes of Health (GM55792, HL58091)
- National Heart, Lung, and Blood Institute (R29HL058091, R37HL058091, HL58091, R01HL058091)
- National Institute of General Medical Sciences (R29GM055792, GM55792, R01GM055792)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- hemoglobin, nitrite reductase, nitric oxide production, hypoxic vasodilation, oxygen sensing, allosteric transition, pH control, oxygen saturation
- MeSH terms
- Allosteric Regulation, Allosteric Site, Animals, Hypoxia, Hemoglobins, Horses, Humans, Hydrogen-Ion Concentration, Kinetics, Nitric Oxide, Nitrite Reductases, Nitrites, Oxidation-Reduction, Vasodilation, Protein Structure, Tertiary
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