Nitrite reduction: a ubiquitous function from a pre-aerobic past
Abstract
In eukaryotes, small amounts of nitrite confer cytoprotection against ischemia/reperfusion-related tissue damage in vivo, possibly via reduction to nitric oxide (NO) and inhibition of mitochondrial function. Several hemeproteins are involved in this protective mechanism, starting with deoxyhemoglobin, which is capable of reducing nitrite. In facultative aerobic bacteria, such as Pseudomonas aeruginosa, nitrite is reduced to NO by specialized heme-containing enzymes called cd(1) nitrite reductases. The details of their catalytic mechanism are summarized below, together with a hypothesis on the biological role of the unusual d(1)-heme, which, in the reduced state, shows unique properties (very high affinity for nitrite and exceptionally fast dissociation of NO). Our results support the idea that the nitrite-based reactions of contemporary eukaryotes are a vestige of earlier bacterial biochemical pathways. The evidence that nitrite reductase activities of enzymes with different cellular roles and biochemical features still exist today highlights the importance of nitrite in cellular homeostasis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Eukaryotic cells employ enzymatic nitrite reduction.
“While it has been well known that prokaryotes contain numerous nitrite/nitrate reductases, the confirmation that eukaryotic cells employ enzymatic nitrite reduction has only recently become clear [129].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [129]
Cites
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
Nitric oxide synthases: structure, function and inhibition
ALDERTON, W. K., COOPER, C. E., & KNOWLES, R. G. (2001) · Biochemical Journal · doi:10.1042/bj3570593 · Cited by 4,110 · see citing works
Nitric oxide synthases: structure, function and inhibition
ALDERTON, W. K., Cooper, C. E., & Knowles, R. G. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3570593 · Cited by 4,106 · see citing works
Cell biology and molecular basis of denitrification
Zumft, W. G. (1997) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.61.4.533-616.1997 · Cited by 3,483 · see citing works
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · cited 2× · see citing works
“We support the hypothesis, already put forward by other authors,((15,63,64,67)) that the nitrite-based reactions of contemporary mammalian cells are a vestige of earlier biochemical pathways of prokaryotes.”
BackgroundResultThe reaction of NO with superoxide
Huie, R. E., & Padmaja, S. (1993) · Free Radical Research Communications · doi:10.3109/10715769309145868 · Cited by 2,121 · 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
Role of nitric oxide synthesis in macrophage antimicrobial activity
Nathan, C. F., & Hibbs, J. B. (1991) · Current Opinion in Immunology · doi:10.1016/0952-7915(91)90079-g · Cited by 1,523 · see citing works
Palmer, R. M. J., Rees, D. D., Ashton, D. S., & Moncada, S. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)81362-7 · Cited by 1,348 · see citing works
Cleeter, M. W. J., Cooper, J. M., Darley-Usmar, V. M., Moncada, S., & Schapira, A. H. V. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00424-2 · Cited by 1,241 · see citing works
Brown, G. C., & Cooper, C. E. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01290-3 · Cited by 1,055 · see citing works
Clementi, E., Brown, G. C., Feelisch, M., & Moncada, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7631 · Cited by 863 · see citing works
Moore, G. R. (2002) · Journal of Organometallic Chemistry · doi:10.1016/s0022-328x(02)01715-1 · Cited by 699 · see citing works
The emerging biology of the nitrite anion
Gladwin, M. T., Schechter, A. N., Kim-Shapiro, D. B., Patel, R. P., Hogg, N., Shiva, S., Cannon, R. O., Kelm, M., Wink, D. A., Espey, M. G., et al. (2005) · Nature Chemical Biology · doi:10.1038/nchembio1105-308 · Cited by 609 · 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
Pseudomonas aeruginosa Anaerobic Respiration in Biofilms
Yoon, S. S., Hennigan, R. F., Hilliard, G. M., Ochsner, U. A., Parvatiyar, K., Kamani, M. C., Allen, H. L., Dekievit, T., Gardner, P. R., Schwab, U. E., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00295-2 · Cited by 587 · see citing works
Dissimilatory Nitrite and Nitric Oxide Reductases
Averill, B. A. (1996) · Chemical Reviews · doi:10.1021/cr950056p · Cited by 545 · 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
Castello, P. R., David, P. S., McClure, T., Crook, Z., & Poyton, R. O. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.011 · Cited by 495 · see citing works
Nitric oxide synthesis and signalling in plants
Wilson, I. D., Neill, S. J., & Hancock, J. T. (2007) · Plant Cell & Environment · doi:10.1111/j.1365-3040.2007.01761.x · Cited by 479 · see citing works
Hendgen-Cotta, U. B., Merx, M. W., Shiva, S., Schmitz, J., Becher, S., Klare, J. P., Steinhoff, H.-J., Goedecke, A., Schrader, J., Gladwin, M. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801336105 · Cited by 418 · see citing works
Mendel, R. R., & Bittner, F. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.03.013 · Cited by 356 · see citing works
Hassett, D. J., Cuppoletti, J., Trapnell, B. C., Lymar, S. V., Rowe, J. J., Yoon, S. S., Hilliard, G. M., Parvatiyar, K., Kamani, M. C., Wozniak, D. J., et al. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00152-7 · Cited by 306 · see citing works
Nitric Oxide: A Unique Endogenous Signaling Molecule in Vascular Biology
Ignarro, L. J. (1999) · Bioscience Reports · doi:10.1023/a:1020150124721 · Cited by 305 · see citing works
The functional nitrite reductase activity of the heme-globins
Gladwin, M. T., & Kim-Shapiro, D. B. (2008) · Blood · doi:10.1182/blood-2008-01-115261 · Cited by 293 · see citing works
Cooperativity in the dissociation of nitric oxide from hemoglobin.
Moore, E. G., & Gibson, Q. H. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33557-3 · Cited by 292 · see citing works
NO-mediated cytoprotection: Instant adaptation to oxidative stress in bacteria
Gusarov, I., & Nudler, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504307102 · Cited by 282 · see citing works
Methods in nitric oxide research
Meyerhoff, M. E., & Howland, J. L. (1997) · Biochemical Education · doi:10.1016/s0307-4412(97)84462-7 · Cited by 277 · see citing works
A possible nitrogen crisis for Archaean life due to reduced nitrogen fixation by lightning
Navarro-González, R., McKay, C. P., & Mvondo, D. N. (2001) · Nature · doi:10.1038/35083537 · Cited by 272 · see citing works
Nitric 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
Nitrite in nitric oxide biology: Cause or consequence?
Bryan, N. S. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.019 · Cited by 260 · see citing works
Nitration of a peptide phytotoxin by bacterial nitric oxide synthase
Kers, J. A., Wach, M. J., Krasnoff, S. B., Widom, J., Cameron, K. D., Bukhalid, R. A., Gibson, D. M., Crane, B. R., & Loria, R. (2004) · Nature · doi:10.1038/nature02504 · Cited by 253 · see citing works
Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands
Palacios‐Callender, M., Knowles, R. G., Palmer, R. M. J., & Moncada, S. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(89)80037-3 · Cited by 237 · see citing works
An <i>S</i> -nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate
Angelo, M., Singel, D. J., & Stamler, J. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600942103 · Cited by 233 · see citing works
Catalytic generation of N2O3 by the concerted nitrite reductase and anhydrase activity of hemoglobin
Basu, S., Grubina, R., Huang, J., Conradie, J., Huang, Z., Jeffers, A., Jiang, A., He, X., Azarov, I., Seibert, R., et al. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.46 · Cited by 224 · see citing works
Tissue Processing of Nitrite in Hypoxia
Feelisch, M., Fernandez, B. O., Bryan, N. S., Garcia-Saura, M. F., Bauer, S., Whitlock, D. R., Ford, P. C., Janero, D. R., Rodriguez, J., & Ashrafian, H. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806654200 · Cited by 218 · see citing works
Nitrite reductase activity of cytochrome c
Basu, S., Azarova, N. A., Font, M. D., King, S. B., Hogg, N., Gladwin, M. T., Shiva, S., & Kim-Shapiro, D. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806934200 · Cited by 214 · see citing works
Yoon, S. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24684 · Cited by 212 · see citing works
Webb, A. J., Milsom, A. B., Rathod, K. S., Chu, W. L., Qureshi, S., Lovell, M. J., Lecomte, F. M. J., Perrett, D., Raimondo, C., Khoshbin, E., et al. (2008) · Circulation Research · doi:10.1161/circresaha.108.175810 · Cited by 203 · see citing works
Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics
DEZFULIAN, C., RAAT, N., SHIVA, S., & GLADWIN, M. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.05.001 · Cited by 198 · cited 1× · see citing works
“For example, NO production is associated with cytoprotection against ischemia/ reperfusion (IR) injury((14)) by inhibiting not only complex IV but also complex I of the respiratory chain.”
BackgroundGladwin, M. T., Grubina, R., & Doyle, M. P. (2009) · Accounts of Chemical Research · doi:10.1021/ar800089j · Cited by 194 · see citing works
Class-1 hemoglobins, nitrate and NO levels in anoxic maize cell-suspension cultures
Rivoal, J., Hill, R. D., Dordas, C. A., & Hasinoff, B. B. (2004) · Planta · doi:10.1007/s00425-004-1212-y · Cited by 185 · see citing works
Therapeutic Uses of Inorganic Nitrite and Nitrate: From the Past to the Future
Butler, A. R., & Feelisch, M. (2008) · Circulation · doi:10.1161/circulationaha.107.753814 · Cited by 184 · see citing works
Kharitonov, V. G., Sharma, V. S., Magde, D., & Koesling, D. (1997) · Biochemistry · doi:10.1021/bi970201o · Cited by 171 · see citing works
Bacterial Nitric-oxide Synthases Operate without a Dedicated Redox Partner
Gusarov, I., Starodubtseva, M., Wang, Z.-Q., McQuade, L. E., Lippard, S. J., Stuehr, D. J., & Nudler, E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710178200 · Cited by 161 · see citing works
Was nitric oxide the first deep electron sink?
Ducluzeau, A., van Lis, R., Duval, S., Schoepp‐Cothenet, B., Russell, M. J., & Nitschke, W. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.10.005 · Cited by 160 · see citing works
Giuffrè, A., Stubauer, G., Sarti, P., Brunori, M., Zumft, W. G., Buse, G., & Soulimane, T. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14718 · Cited by 154 · see citing works
Self-citationGrubina, R., Huang, Z., Shiva, S., Joshi, M. S., Azarov, I., Basu, S., Ringwood, L. A., Jiang, A., Hogg, N., Kim‐Shapiro, D. B., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700546200 · Cited by 147 · see citing works
Nurizzo, D., Silvestrini, M. C., Mathieu, M., et al. (1997) · Structure · doi:10.1016/s0969-2126(97)00267-0 · Cited by 133 · see citing works
Vijgenboom, E., Busch, J. E., & Canters, G. W. (1997) · Microbiology · doi:10.1099/00221287-143-9-2853 · Cited by 127 · see citing works
Castello, P. R., Woo, D. K., Ball, K., Wojcik, J., Liu, L., & Poyton, R. O. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709461105 · Cited by 121 · see citing works
Assembly and regulation of NADPH oxidase and nitric oxide synthase
Bastian, N. R., & Hibbs, J. B. (1994) · Current Opinion in Immunology · doi:10.1016/0952-7915(94)90044-2 · Cited by 120 · see citing works
Yamanaka, T., Ota, A., & OKUNUKI, K. (1961) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(61)90442-5 · Cited by 120 · see citing works
van den Berg, N. J., Ossip, M. S., Hederos, C., Anttila, H., Ribeiro, B. L., & Davies, P. I. (2000) · Pediatric Pulmonology · doi:10.1002/1099-0496(200008)30:2 · Cited by 108 · see citing works
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 · see citing works
Carr, G., & Ferguson, S. J. (1990) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(90)90178-7 · Cited by 99 · see citing works
Platt, M. D., Schurr, M. J., Sauer, K., Vázquez, G. J., Kukavica‐Ibrulj, I., Potvin, É., Lévesque, R. C., Fedynak, A., Brinkman, F. S. L., Schurr, J. R., et al. (2008) · Journal of Bacteriology · doi:10.1128/jb.01683-07 · Cited by 94 · see citing works
Cutruzzolà, F., Brown, K., Wilson, E. K., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.041365298 · Cited by 90 · see citing works
Self-citationNurizzo, D., Cutruzzolà, F., Arese, M., et al. (1998) · Biochemistry · doi:10.1021/bi981348y · Cited by 82 · see citing works
Self-citationEnzyme diversity and mosaic gene organization in denitrification
Zumft, W. G., & Körner, H. (1997) · Antonie van Leeuwenhoek · doi:10.1023/a:1000112008026 · Cited by 74 · see citing works
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 · see citing works
From NO to OO: Nitric Oxide and Dioxygen in Bacterial Respiration
Hendriks, J. H. M., Gohlke, U., & Saraste, M. (1998) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1020547225398 · Cited by 63 · see citing works
Nitrite Reductases in Denitrification
Rinaldo, S., & Cutruzzolà, F. (2007) · Elsevier eBooks · doi:10.1016/b978-044452857-5.50004-7 · Cited by 54 · see citing works
Self-citationCytochrome cd1, Reductive Activation and Kinetic Analysis of a Multifunctional Respiratory Enzyme
Richter, C. D., Allen, J. W. A., Higham, C. W., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108944200 · Cited by 53 · see citing works
ChemInform Abstract: The Chemistry of Nitric Oxide and Redox‐Related Species
Bonner, F. T., & STEDMAN, G. (1997) · ChemInform · doi:10.1002/chin.199715245 · Cited by 53 · see citing works
Why isn't ‘standard’ heme good enough for c-type and d1-type cytochromes?
Allen, J. W. A., Barker, P. D., Daltrop, O., et al. (2005) · Dalton Transactions · doi:10.1039/b508139b · Cited by 51 · see citing works
Cossins, A. R., & Berenbrink, M. (2008) · Nature · doi:10.1038/454416a · Cited by 50 · see citing works
Fast Dissociation of Nitric Oxide from Ferrous Pseudomonas aeruginosa cd1 Nitrite Reductase
Rinaldo, S., Arcovito, A., Brunori, M., & Cutruzzolà, F. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700933200 · Cited by 45 · see citing works
Self-citationAllosteric control of internal electron transfer in cytochrome cd 1 nitrite reductase
Farver, O., Kroneck, P. M. H., Zumft, W. G., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0932693100 · Cited by 39 · see citing works
Farver, O., Brunori, M., Cutruzzolà, F., et al. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2008.12.3937 · Cited by 30 · see citing works
Self-citationNitrite controls the release of nitric oxide in Pseudomonas aeruginosa cd1 nitrite reductase
Rinaldo, S., Brunori, M., & Cutruzzolà, F. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.09.036 · Cited by 21 · see citing works
Self-citationNew insights into the activity of Pseudomonas aeruginosa cd1 nitrite reductase
Rinaldo, S., Arcovito, A., Giardina, G., Castiglione, N., Brunori, M., & Cutruzzolà, F. (2008) · Biochemical Society Transactions · doi:10.1042/bst0361155 · Cited by 18 · see citing works
Self-citationNitrogen-15 nuclear magnetic resonance investigation of nitrite reductase-substrate interaction
Timkovich, R., & Cork, M. S. (1982) · Biochemistry · doi:10.1021/bi00259a012 · Cited by 13 · see citing works
Ancient hemes for ancient catalysts
Rinaldo, S., Brunori, M., & Cutruzzolà, F. (2008) · Plant Signaling & Behavior · doi:10.4161/psb.3.2.5052 · Cited by 12 · see citing works
Self-citationAdman, E. T., & Murphy, M. E. P. (2004) · Handbook of Metalloproteins · doi:10.1002/0470028637.met201 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Maia, L. B., & Moura, J. J. G. (2014) · Chemical Reviews · doi:10.1021/cr400518y · Cited by 401 · see citing works
Inorganic nitrite therapy: historical perspective and future directions
Kevil, C. G., Kolluru, G. K., Pattillo, C. B., & Giordano, T. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.042 · Cited by 113 · see citing works
Nitrite Reductase Activity of Nonsymbiotic Hemoglobins from <i>Arabidopsis thaliana</i>
Tiso, M., Tejero, J., Kenney, C., Frizzell, S., & Gladwin, M. T. (2012) · Biochemistry · doi:10.1021/bi300570v · Cited by 69 · see citing works
- Authors
- Cutruzzolà, F., Rinaldo, S., Castiglione, N., Giardina, G., Pecht, I., & Brunori, M.
- Affiliations
- Sapienza University of Rome (IT)
- Weizmann Institute of Science (IL)
- Corresponding author
- Cutruzzolà, Francesca
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2009-07-16
- Volume
- 31
- Issue
- 8
- Pages
- 885-891
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- OpenAlex
- W2017543986
- Cited by
- 13
- References
- 75
- Citations by year
- 2017: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 4
- FWCI
- 0.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- BioEssays (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Keywords
- nitrite reduction, nitric oxide, deoxyhemoglobin, mitochondrial function, Pseudomonas aeruginosa, catalytic mechanism
- MeSH terms
- Aerobiosis, Bacteria, Eukaryotic Cells, Nitric Oxide, Nitrites, Oxidation-Reduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review