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Record Information
StatusDetected and Quantified
Creation Date2006-08-12 19:53:05 UTC
Update Date2020-05-07 18:05:00 UTC
Secondary Accession Numbers
  • HMDB0032439
  • HMDB03378
  • HMDB32439
Metabolite Identification
Common NameNitric oxide
DescriptionThe 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.; 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).
Endothelium-derived relaxing factorChEBI
Mononitrogen monoxideChEBI
Monoxido de nitrogenoChEBI
Monoxyde d'azoteChEBI
Nitrogen monooxideChEBI
Nitrogen monoxideChEBI
Oxido de nitrogeno(II)ChEBI
Oxido nitricoChEBI
Oxyde azotiqueChEBI
Oxyde nitriqueChEBI
Nitrogen oxideHMDB
Nitrogen protoxideHMDB
Nitrosyl hydrideHMDB
Nitrosyl radicalHMDB
Nitroxide radicalHMDB
Endogenous nitrate vasodilatorMeSH, HMDB
Monoxide, nitrogenMeSH, HMDB
Nitric oxide, endothelium derivedMeSH, HMDB
Nitric oxide, endothelium-derivedMeSH, HMDB
Monoxide, mononitrogenMeSH, HMDB
Vasodilator, endogenous nitrateMeSH, HMDB
Endothelium-derived nitric oxideMeSH, HMDB
Nitrate vasodilator, endogenousMeSH, HMDB
Oxide, nitricMeSH, HMDB
Chemical FormulaNO
Average Molecular Weight30.0061
Monoisotopic Molecular Weight29.997988627
IUPAC Namenitroso
Traditional Namenitric oxide
CAS Registry Number10102-43-9
InChI Identifier
Chemical Taxonomy
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'.
KingdomInorganic compounds
Super ClassHomogeneous non-metal compounds
ClassOther non-metal organides
Sub ClassOther non-metal oxides
Direct ParentOther non-metal oxides
Alternative Parents
  • Other non-metal oxide
  • Inorganic oxide
Molecular FrameworkNot Available
External Descriptors

Route of exposure:


Biological location:


Naturally occurring process:


Industrial application:

Physical Properties
Experimental Properties
Melting Point-163.6 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity2.89 m³·mol⁻¹ChemAxon
Polarizability1.69 ųChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon


Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001i-9000000000-d182bfca83d886821e6d2016-09-22View Spectrum
MSMass Spectrum (Electron Ionization)splash10-004i-9000000000-fb8f363a82c23fe8946f2021-09-05View Spectrum


Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-9000000000-8a2dd9da1fc114d013b32015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-9000000000-8a2dd9da1fc114d013b32015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-8a2dd9da1fc114d013b32015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-9000000000-e998110984a05853a05d2015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9000000000-e998110984a05853a05d2015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-e998110984a05853a05d2015-09-15View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-9000000000-4faa0e3c79683567bab02021-09-08View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-9000000000-4faa0e3c79683567bab02021-09-09View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-4faa0e3c79683567bab02021-09-09View Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Locations
  • Adipose Tissue
  • Adrenal Gland
  • Adrenal Medulla
  • Bladder
  • Brain
  • Epidermis
  • Fibroblasts
  • Intestine
  • Kidney
  • Lung
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Testis
  • Thyroid Gland
Normal Concentrations
BloodDetected and Quantified0.000012 +/- 0.000006 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.05 +/- 0.01 uMAdult (>18 years old)MaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified8.66 +/- 1.07 uMNewborn (0-30 days old)Not SpecifiedNormal details
Abnormal Concentrations
Cerebrospinal Fluid (CSF)Detected and Quantified8.60 +/- 0.49 uMNewborn (0-30 days old)Not SpecifiedHypoxic-ischemic encephalopathy details
Cerebrospinal Fluid (CSF)Detected and Quantified0.99 +/- 0.01 uMAdult (>18 years old)MaleSubarachnoid hemorrhage details
Associated Disorders and Diseases
Disease References
Subarachnoid hemorrhage
  1. Durmaz R, Ozkara E, Kanbak G, Arslan OC, Dokumacioglu A, Kartkaya K, Atasoy MA: Nitric oxide level and adenosine deaminase activity in cerebrospinal fluid of patients with subarachnoid hemorrhage. Turk Neurosurg. 2008 Apr;18(2):157-64. [PubMed:18597230 ]
Hypoxic-ischemic encephalopathy
  1. Gucuyener K, Ergenekon E, Demiryurek T, Erbas D, Ozturk G, Koc E, Atalay Y: Cerebrospinal fluid levels of nitric oxide and nitrotyrosine in neonates with mild hypoxic-ischemic encephalopathy. J Child Neurol. 2002 Nov;17(11):815-8. [PubMed:12585720 ]
Associated OMIM IDs
DrugBank IDDB00435
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID127983
KEGG Compound IDC00533
BiGG IDNot Available
Wikipedia LinkNitric oxide
METLIN IDNot Available
PubChem Compound145068
PDB IDNot Available
ChEBI ID16480
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Synthesis ReferenceMorabito, Paul; Heicklen, Julian. Disproportionation to combination ratios of alkoxy radicals with nitric oxide. Journal of Physical Chemistry (1985), 89(13), 2914-16.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]
  20. 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 ]
  21. 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 ]
  22. Hurford WE: Current status of nitric oxide inhalation. Nihon Kyobu Shikkan Gakkai Zasshi. 1995 Dec;33 Suppl:199-204. [PubMed:8752507 ]
  23. Stephens C, Fawcett TN: Nitric oxide and nursing: a review. J Clin Nurs. 2007 Jan;16(1):67-76. [PubMed:17181668 ]
  24. 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 ]
  25. (). EAFUS: Everything Added to Food in the United States.. .


General function:
Involved in oxidoreductase activity
Specific function:
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.
Gene Name:
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Molecular weight:
L-Arginine + NADPH + Oxygen → Citrulline + Nitric oxide + NADP + Waterdetails
NADPH + N(omega)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
L-Arginine + Oxygen + NADPH + Hydrogen Ion → Nitric oxide + Citrulline + NADP + Waterdetails
General function:
Involved in oxidoreductase activity
Specific function:
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
Gene Name:
Uniprot ID:
Molecular weight:
L-Arginine + NADPH + Oxygen → Citrulline + Nitric oxide + NADP + Waterdetails
NADPH + N(omega)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
L-Arginine + Oxygen + NADPH + Hydrogen Ion → Nitric oxide + Citrulline + NADP + Waterdetails
General function:
Involved in oxidoreductase activity
Specific function:
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
Gene Name:
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Molecular weight:
L-Arginine + NADPH + Oxygen → Citrulline + Nitric oxide + NADP + Waterdetails
NADPH + N(omega)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Waterdetails
L-Arginine + Oxygen + NADPH + Hydrogen Ion → Nitric oxide + Citrulline + NADP + Waterdetails
General function:
Involved in iron ion binding
Specific function:
LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure
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General function:
Involved in endothelin A receptor binding
Specific function:
Endothelins are endothelium-derived vasoconstrictor peptides
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General function:
Involved in oxidoreductase activity
Specific function:
Not Available
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General function:
Involved in microtubule-based process
Specific function:
Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity
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