| Record Information |
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| Version | 5.0 |
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| Status | Detected and Quantified |
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| Creation Date | 2006-08-12 19:53:05 UTC |
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| Update Date | 2020-05-07 18:05:00 UTC |
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| HMDB ID | HMDB0003378 |
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| Secondary Accession Numbers | - HMDB0032439
- HMDB03378
- HMDB32439
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| Metabolite Identification |
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| Common Name | Nitric oxide |
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| Description | The biologically active molecule nitric oxide (NO) is a simple, membrane-permeable gas with unique chemistry. It is formed by the conversion of L-arginine to L-citrulline, with the release of NO. The enzymatic oxidation of L-arginine to L-citrulline takes place in the presence of oxygen and NADPH using flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), heme, thiol, and tetrahydrobiopterin as cofactors. The enzyme responsible for the generation of NO is nitric oxide synthase (E.C. 1.7.99.7; NOS). Three NOS isoforms have been described and shown to be encoded on three distinct genes: neuronal NOS (nNOS, NOS type I), inducible NOS (NOS type II), and endothelial NOS (eNOS, NOS type III). Two of them are constitutively expressed and dependent on the presence of calcium ions and calmodulin to function (nNOS and eNOS), while iNOS is considered non-constitutive and calcium-independent. However, experience has shown that constitutive expression of nNOS and eNOS is not as rigid as previously thought (i.e. either present or absent), but can be dynamically controlled during development and in response to injury. Functionally, NO may act as a hormone, neurotransmitter, paracrine messenger, mediator, cytoprotective molecule, and cytotoxic molecule. NO has multiple cellular molecular targets. It influences the activity of transcription factors, modulates upstream signaling cascades, mRNA stability and translation, and processes the primary gene products. In the brain, many processes are linked to NO. NO activates its receptor, soluble guanylate cyclase by binding to it. The stimulation of this enzyme leads to increased synthesis of the second messenger, cGMP, which in turn activates cGMP-dependent kinases in target cells. NO exerts a strong influence on glutamatergic neurotransmission by directly interacting with the N-methyl-D-aspartate (NMDA) receptor. Neuronal NOS is connected to NMDA receptors (see below) and sharply increases NO production following activation of this receptor. Thus, the level of endogenously produced NO around NMDA synapses reflects the activity of glutamate-mediated neurotransmission. However, there is recent evidence showing that non-NMDA glutamate receptors (i.e. AMPA and type I metabotropic receptors) also contribute to NO generation. Besides its influence on glutamate, NO is known to have effects on the storage, uptake and/or release of most other neurotransmitters in the CNS (acetylcholine, dopamine, noradrenaline, GABA, taurine, and glycine) as well as of certain neuropeptides. Finally, since NO is a highly diffusible molecule, it may reach extrasynaptic receptors at target cell membranes that are some distance away from the place of NO synthesis. NO is thus capable of mediating both synaptic and nonsynaptic communication processes. NO is a potent vasodilator (a major endogenous regulator of vascular tone), and an important endothelium-dependent relaxing factor. NO is synthesized by NO synthases (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls suggest that ADMA has a role in vascular dilatation and blood pressure changes. Several studies show an increase in ADMA levels in pregnancies complicated with preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical symptoms have developed; these findings suggest that ADMA has a role in the pathogenesis of preeclampsia. In some pulmonary hypertensive states such as ARDS, the production of endogenous NO may be impaired. Nitric oxide inhalation selectively dilates the pulmonary circulation. Significant systemic vasodilation does not occur because NO is inactivated by rapidly binding to hemoglobin. In an injured lung with pulmonary hypertension, inhaled NO produces local vasodilation of well-ventilated lung units and may "steal" blood flow away from unventilated regions. This reduces intrapulmonary shunting and may improve systemic arterial oxygenation. Nitric oxide is a chemical mediator fundamental in the maintenance of adequate tissue perfusion and effective cardiovascular function. The use of nitrates is well established as pharmacological agents but it is only recently that it has been recognized that they act as a source of nitric oxide (PMID: 16966108 , 8752507 , 17181668 , 16005189 ). Nitric oxide is used as a food additive (EAFUS: Everything Added to Food in the United States). |
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| Structure | |
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| Synonyms | | Value | Source |
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| (NO)(.) | ChEBI | | [NO] | ChEBI | | EDRF | ChEBI | | Endothelium-derived relaxing factor | ChEBI | | Mononitrogen monoxide | ChEBI | | Monoxido de nitrogeno | ChEBI | | Monoxyde d'azote | ChEBI | | Nitrogen monooxide | ChEBI | | Nitrogen monoxide | ChEBI | | Nitrosyl | ChEBI | | NO | ChEBI | | (.)NO | ChEBI | | NO(.) | ChEBI | | Oxido de nitrogeno(II) | ChEBI | | Oxido nitrico | ChEBI | | Oxyde azotique | ChEBI | | Oxyde nitrique | ChEBI | | Stickstoff(II)-oxid | ChEBI | | Stickstoffmonoxid | ChEBI | | INOmax | Kegg | | Nitrogen oxide | HMDB | | Nitrogen protoxide | HMDB | | Nitrosyl hydride | HMDB | | Nitrosyl radical | HMDB | | Nitroxide radical | HMDB | | Nitroxyl | HMDB | | Endogenous nitrate vasodilator | MeSH, HMDB | | Monoxide, nitrogen | MeSH, HMDB | | Nitric oxide, endothelium derived | MeSH, HMDB | | Nitric oxide, endothelium-derived | MeSH, HMDB | | Monoxide, mononitrogen | MeSH, HMDB | | Vasodilator, endogenous nitrate | MeSH, HMDB | | Endothelium-derived nitric oxide | MeSH, HMDB | | Nitrate vasodilator, endogenous | MeSH, HMDB | | Oxide, nitric | MeSH, HMDB |
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| Chemical Formula | NO |
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| Average Molecular Weight | 30.0061 |
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| Monoisotopic Molecular Weight | 29.997988627 |
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| IUPAC Name | nitroso |
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| Traditional Name | nitric oxide |
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| CAS Registry Number | 10102-43-9 |
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| SMILES | [N]=O |
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| InChI Identifier | InChI=1S/NO/c1-2 |
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| InChI Key | MWUXSHHQAYIFBG-UHFFFAOYSA-N |
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| Chemical Taxonomy |
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| Description | Belongs to the class of inorganic compounds known as other non-metal oxides. These are inorganic compounds containing an oxygen atom of an oxidation state of -2, in which the heaviest atom bonded to the oxygen belongs to the class of 'other non-metals'. |
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| Kingdom | Inorganic compounds |
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| Super Class | Homogeneous non-metal compounds |
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| Class | Other non-metal organides |
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| Sub Class | Other non-metal oxides |
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| Direct Parent | Other non-metal oxides |
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| Alternative Parents | |
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| Substituents | - Other non-metal oxide
- Inorganic oxide
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| Molecular Framework | Not Available |
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| External Descriptors | |
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| Ontology |
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| Not Available | Not Available |
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| Physical Properties |
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| State | Liquid |
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| Experimental Molecular Properties | | Property | Value | Reference |
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| Melting Point | -163.6 °C | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | Not Available | Not Available | | LogP | Not Available | Not Available |
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| Experimental Chromatographic Properties | Not Available |
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| Predicted Molecular Properties | |
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| Predicted Chromatographic Properties | Predicted Collision Cross Sections| Predictor | Adduct Type | CCS Value (Å2) | Reference |
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| DeepCCS | [M+H]+ | 110.435 | 30932474 | | DeepCCS | [M-H]- | 108.681 | 30932474 | | DeepCCS | [M-2H]- | 143.856 | 30932474 | | DeepCCS | [M+Na]+ | 117.187 | 30932474 |
Predicted Kovats Retention IndicesUnderivatized| Metabolite | SMILES | Kovats RI Value | Column Type | Reference |
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| Nitric oxide | [N]=O | 713.9 | Standard polar | 33892256 | | Nitric oxide | [N]=O | 279.7 | Standard non polar | 33892256 | | Nitric oxide | [N]=O | 345.9 | Semi standard non polar | 33892256 |
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| General References | - Kaynar 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. [PubMed:16112416 ]
- Noris 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. [PubMed:14744923 ]
- Moon A: Influence of nitric oxide signalling pathways on pre-contracted human detrusor smooth muscle in vitro. BJU Int. 2002 Jun;89(9):942-9. [PubMed:12010245 ]
- Muerkoster 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. [PubMed:14973050 ]
- Huledal 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. [PubMed:15900289 ]
- Brown 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. [PubMed:16626981 ]
- Santoro 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. [PubMed:11851622 ]
- Browning 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. [PubMed:10644746 ]
- Heym 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. [PubMed:7508210 ]
- Neri 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. [PubMed:16753839 ]
- Atiya 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. [PubMed:8751600 ]
- Kim 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. [PubMed:7679408 ]
- Nichols 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. [PubMed:7523222 ]
- Reitz 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. [PubMed:15041118 ]
- Huguenin 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. [PubMed:15670893 ]
- Stack WA, Filipowicz B, Hawkey CJ: Nitric oxide donating compounds stimulate human colonic ion transport in vitro. Gut. 1996 Jul;39(1):93-9. [PubMed:8881817 ]
- Khanna 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. [PubMed:15961106 ]
- Calka 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. [PubMed:16584085 ]
- Kublickiene 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. [PubMed:9396927 ]
- Ormerod 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. [PubMed:10469339 ]
- Slaghekke 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. [PubMed:16966108 ]
- Hurford WE: Current status of nitric oxide inhalation. Nihon Kyobu Shikkan Gakkai Zasshi. 1995 Dec;33 Suppl:199-204. [PubMed:8752507 ]
- Stephens C, Fawcett TN: Nitric oxide and nursing: a review. J Clin Nurs. 2007 Jan;16(1):67-76. [PubMed:17181668 ]
- Bernstein HG, Bogerts B, Keilhoff G: The many faces of nitric oxide in schizophrenia. A review. Schizophr Res. 2005 Oct 1;78(1):69-86. [PubMed:16005189 ]
- (). EAFUS: Everything Added to Food in the United States.. .
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