2.02012-05-31 13:58:47 -06002015-09-13 12:56:13 -0600ECMDB03378M2MDB000495Nitric oxideNitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in biological systems. It is also cytotoxic. Mononitrogen monoxideNitric oxideNitrogen monoxideNitrogen oxideNitrogen protoxideNitrosyl hydrideNitrosyl radicalNitroxide radicalNitroxylNONO30.006129.997988627nitrosonitric oxide10102-43-9[N]=OInChI=1S/NO/c1-2MWUXSHHQAYIFBG-UHFFFAOYSA-NGasCytosolExtra-organismPeriplasmmelting_point-163.6 oClogp-0.35ChemAxonpka_strongest_basic-2.9ChemAxoniupacnitrosoChemAxonaverage_mass30.0061ChemAxonmono_mass29.997988627ChemAxonsmiles[N]=OChemAxonformulaNOChemAxoninchiInChI=1S/NO/c1-2ChemAxoninchikeyMWUXSHHQAYIFBG-UHFFFAOYSA-NChemAxonpolar_surface_area34.14ChemAxonrefractivity2.89ChemAxonpolarizability1.69ChemAxonrotatable_bond_count0ChemAxonacceptor_count2ChemAxondonor_count0ChemAxonphysiological_charge0ChemAxonformal_charge0ChemAxonArginine and proline metabolismec00330Nitrogen metabolism
The biological process of the nitrogen cycle is a complex interplay among many microorganisms catalyzing different reactions, where nitrogen is found in various oxidation states ranging from +5 in nitrate to -3 in ammonia.
The ability of fixing atmospheric nitrogen by the nitrogenase enzyme complex is present in restricted prokaryotes (diazotrophs). The other reduction pathways are assimilatory nitrate reduction and dissimilatory nitrate reduction both for conversion to ammonia, and denitrification. Denitrification is a respiration in which nitrate or nitrite is reduced as a terminal electron acceptor under low oxygen or anoxic conditions, producing gaseous nitrogen compounds (N2, NO and N2O) to the atmosphere.
Nitrate can be introduced into the cytoplasm through a nitrate:nitrite antiporter NarK or a nitrate / nitrite transporter NarU. Nitrate is then reduced by a Nitrate Reductase resulting in the release of water, an acceptor and a Nitrite. Nitrite can also be introduced into the cytoplasm through a nitrate:nitrite antiporter NarK
Nitrite can be reduced a NADPH dependent nitrite reductase resulting in water and NAD and Ammonia.
Nitrite can interact with hydrogen ion, ferrocytochrome c through a cytochrome c-552 ferricytochrome resulting in the release of ferricytochrome c, water and ammonia
Another process by which ammonia is produced is by a reversible reaction of hydroxylamine with a reduced acceptor through a hydroxylamine reductase resulting in an acceptor, water and ammonia.
Water and carbon dioxide react through a carbonate dehydratase resulting in carbamic acid. This compound reacts spontaneously with hydrogen ion resulting in the release of carbon dioxide and ammonia. Carbon dioxide can interact with water through a carbonic anhydrase resulting in hydrogen carbonate. This compound interacts with cyanate and hydrogen ion through a cyanate hydratase resulting in a carbamic acid.
Ammonia can be metabolized by reacting with L-glutamine and ATP driven glutamine synthetase resulting in ADP, phosphate and L-glutamine. The latter compound reacts with oxoglutaric acid and hydrogen ion through a NADPH dependent glutamate synthase resulting in the release of NADP and L-glutamic acid. L-glutamic acid reacts with water through a NADP-specific glutamate dehydrogenase resulting in the release of oxoglutaric acid, NADPH, hydrogen ion and ammonia.
PW000755ec00910MetabolicMicrobial metabolism in diverse environmentsec01120Specdb::CMs3342Specdb::CMs150063Specdb::MsMs26135Specdb::MsMs26136Specdb::MsMs26137Specdb::MsMs32693Specdb::MsMs32694Specdb::MsMs32695Specdb::MsMs2688425Specdb::MsMs2688426Specdb::MsMs2688427HMDB03378945127983C0053316480NITRIC-OXIDENitric oxideKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510Kaynar H, Meral M, Turhan H, Keles M, Celik G, Akcay F: Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase activities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer. Cancer Lett. 2005 Sep 28;227(2):133-9. Epub 2005 Jan 8.16112416Noris M, Todeschini M, Cassis P, Pasta F, Cappellini A, Bonazzola S, Macconi D, Maucci R, Porrati F, Benigni A, Picciolo C, Remuzzi G: L-arginine depletion in preeclampsia orients nitric oxide synthase toward oxidant species. Hypertension. 2004 Mar;43(3):614-22. Epub 2004 Jan 26.14744923Moon A: Influence of nitric oxide signalling pathways on pre-contracted human detrusor smooth muscle in vitro. BJU Int. 2002 Jun;89(9):942-9.12010245Muerkoster S, Wegehenkel K, Arlt A, Witt M, Sipos B, Kruse ML, Sebens T, Kloppel G, Kalthoff H, Folsch UR, Schafer H: Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin-1beta. Cancer Res. 2004 Feb 15;64(4):1331-7.14973050Huledal G, Jonzon B, Malmenas M, Hedman A, Andersson LI, Odlind B, Brater DC: Renal effects of the cyclooxygenase-inhibiting nitric oxide donator AZD3582 compared with rofecoxib and naproxen during normal and low sodium intake. Clin Pharmacol Ther. 2005 May;77(5):437-50.15900289Brown DA, Canning MT, Nay SL, Pena AV, Yarosh DB: Bicyclic monoterpene diols stimulate release of nitric oxide from skin cells, increase microcirculation, and elevate skin temperature. Nitric Oxide. 2006 Aug;15(1):70-6. Epub 2006 Apr 19.16626981Santoro G, Romeo C, Impellizzeri P, Ientile R, Cutroneo G, Trimarchi F, Pedale S, Turiaco N, Gentile C: Nitric oxide synthase patterns in normal and varicocele testis in adolescents. BJU Int. 2001 Dec;88(9):967-73.11851622Browning DD, McShane MP, Marty C, Ye RD: Nitric oxide activation of p38 mitogen-activated protein kinase in 293T fibroblasts requires cGMP-dependent protein kinase. J Biol Chem. 2000 Jan 28;275(4):2811-6.10644746Heym C, Colombo-Benckmann M, Mayer B: Immunohistochemical demonstration of the synthesis enzyme for nitric oxide and of comediators in neurons and chromaffin cells of the human adrenal medulla. Ann Anat. 1994 Jan;176(1):11-6.7508210Neri S, Signorelli S, Pulvirenti D, Mauceri B, Cilio D, Bordonaro F, Abate G, Interlandi D, Misseri M, Ignaccolo L, Savastano M, Azzolina R, Grillo C, Messina A, Serra A, Tsami A: Oxidative stress, nitric oxide, endothelial dysfunction and tinnitus. Free Radic Res. 2006 Jun;40(6):615-8.16753839Atiya A, Cohen G, Ignarro L, Brunicardi FC: Nitric oxide regulates insulin secretion in the isolated perfused human pancreas via a cholinergic mechanism. Surgery. 1996 Aug;120(2):322-7.8751600Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I: Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest. 1993 Feb;91(2):437-42.7679408Nichols K, Staines W, Krantis A: Neural sites of the human colon colocalize nitric oxide synthase-related NADPH diaphorase activity and neuropeptide Y. Gastroenterology. 1994 Oct;107(4):968-75.7523222Reitz A, Knapp PA, Muntener M, Schurch B: Oral nitric oxide donors: a new pharmacological approach to detrusor-sphincter dyssynergia in spinal cord injured patients? Eur Urol. 2004 Apr;45(4):516-20.15041118Huguenin S, Vacherot F, Fleury-Feith J, Riffaud JP, Chopin DK, Bolla M, Jaurand MC: Evaluation of the antitumoral potential of different nitric oxide-donating non-steroidal anti-inflammatory drugs (NO-NSAIDs) on human urological tumor cell lines. Cancer Lett. 2005 Feb 10;218(2):163-70.15670893Stack WA, Filipowicz B, Hawkey CJ: Nitric oxide donating compounds stimulate human colonic ion transport in vitro. Gut. 1996 Jul;39(1):93-9.8881817Khanna A, Cowled PA, Fitridge RA: Nitric oxide and skeletal muscle reperfusion injury: current controversies (research review). J Surg Res. 2005 Sep;128(1):98-107.15961106Calka J: The role of nitric oxide in the hypothalamic control of LHRH and oxytocin release, sexual behavior and aging of the LHRH and oxytocin neurons. Folia Histochem Cytobiol. 2006;44(1):3-12.16584085Kublickiene KR, Cockell AP, Nisell H, Poston L: Role of nitric oxide in the regulation of vascular tone in pressurized and perfused resistance myometrial arteries from term pregnant women. Am J Obstet Gynecol. 1997 Nov;177(5):1263-9.9396927Ormerod AD, Copeland P, Hay I, Husain A, Ewen SW: The inflammatory and cytotoxic effects of a nitric oxide releasing cream on normal skin. J Invest Dermatol. 1999 Sep;113(3):392-7.10469339Slaghekke F, Dekker G, Jeffries B: Endogenous inhibitors of nitric oxide and preeclampsia: a review. J Matern Fetal Neonatal Med. 2006 Aug;19(8):447-52.16966108Hurford WE: Current status of nitric oxide inhalation. Nihon Kyobu Shikkan Gakkai Zasshi. 1995 Dec;33 Suppl:199-204.8752507Stephens C, Fawcett TN: Nitric oxide and nursing: a review. J Clin Nurs. 2007 Jan;16(1):67-76.17181668Bernstein HG, Bogerts B, Keilhoff G: The many faces of nitric oxide in schizophrenia. A review. Schizophr Res. 2005 Oct 1;78(1):69-86.16005189Morabito, Paul; Heicklen, Julian. Disproportionation to combination ratios of alkoxy radicals with nitric oxide. Journal of Physical Chemistry (1985), 89(13), 2914-16.http://hmdb.ca/system/metabolites/msds/000/002/959/original/HMDB03378.pdf?1358463213FlavohemoproteinP24232HMP_ECOLIhmphttp://ecmdb.ca/proteins/P24232.xmlNitric oxide reductase FlRd-NAD(+) reductaseP37596NORW_ECOLInorWhttp://ecmdb.ca/proteins/P37596.xmlAnaerobic nitric oxide reductase flavorubredoxinQ46877NORV_ECOLInorVhttp://ecmdb.ca/proteins/Q46877.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlHydrogen ion + NADH + 2 Nitric oxide > Water + Nitrous oxide + NADNADH + 2 Nitric oxide + 2 Oxygen > Hydrogen ion + NAD +2 NitrateNADPH + 2 Nitric oxide + 2 Oxygen > Hydrogen ion + NADP +2 Nitrate2 [4Fe-4S] iron-sulfur cluster + 2 Hydrogen ion + 2 Nitric oxide >2 [3Fe-4S] damaged iron-sulfur cluster +2 Fe3+ + Water + Nitrous oxideNitrous oxide + Water + Cytochromes-C-Oxidized Nitric oxide + Hydrogen ion + Cytochromes-C-ReducedNITRIC-OXIDE-REDUCTASE-RXNNAD(P)H + Nitric oxide + Oxygen > NAD(P)<sup>+</sup> + Nitrate + Hydrogen ionR621-RXN2 Nitric oxide + 2 Oxygen + NAD(P)H >2 Nitrate + NAD(P)(+)Nitric oxide + 2 Oxygen + NADH + NADPH <>2 Nitrate + NAD + NADP + Hydrogen ionR05724 R05725