Human Metabolome Database Version 3.5

Showing metabocard for Nitric oxide (HMDB03378)

Record Information
Version 3.5
Creation Date 2006-08-12 13:53:05 -0600
Update Date 2013-05-29 13:38:08 -0600
HMDB ID HMDB03378
Secondary Accession Numbers None
Metabolite Identification
Common Name Nitric oxide
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 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 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, and 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 at some distance 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 Link_out, 8752507 Link_out, 17181668 Link_out, 16005189 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. Mononitrogen monoxide
  2. Nitric oxide
  3. Nitrogen monoxide
  4. Nitrogen oxide
  5. Nitrogen protoxide
  6. Nitrosyl hydride
  7. Nitrosyl radical
  8. Nitroxide radical
  9. Nitroxyl
Chemical Formula NO
Average Molecular Weight 30.0061
Monoisotopic Molecular Weight 29.997988627
IUPAC Name hydroxyamine
Traditional IUPAC Name hydroxyamine
CAS Registry Number 10102-43-9
SMILES N#[O]
InChI Identifier InChI=1S/NO/c1-2
InChI Key MWUXSHHQAYIFBG-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Inorganic Compounds
Super Class Homogeneous Non-metal Compounds
Class Other Non-metal Organides
Sub Class Other Non-metal Oxides
Other Descriptors
  • inorganic radical(ChEBI)
  • nitrogen oxide(ChEBI)
  • reactive nitrogen species(ChEBI)
  • reactive oxygen species(ChEBI)
Substituents
  • N/A
Direct Parent Other Non-metal Oxides
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Arginine and proline metabolism
Application Not Available
Cellular locations
  • Cytoplasm
  • Extracellular
Physical Properties
State Gas
Experimental Properties
Property Value Reference
Melting Point -163.6 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Hydrogen Acceptor Count 0 ChemAxon
Hydrogen Donor Count 0 ChemAxon
Polar Surface Area 23.79 A2 ChemAxon
Rotatable Bond Count 0 ChemAxon
Refractivity 26.23 ChemAxon
Polarizability 1.63 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • Muscle
  • Skeletal Muscle
  • Bladder
  • Fibroblasts
  • Intestine
  • Neuron
  • Pancreas
  • Placenta
  • Testes
  • Kidney
  • Thyroid Gland
  • Brain
  • Myelin
  • Prostate
  • Adrenal Gland
  • Fetus
  • Skin
  • Adipose Tissue
  • Adrenal Medulla
  • Lung
  • Nerve Cells
  • Platelet
  • Spleen
Pathways
Name SMPDB Link KEGG Link
Arginine and Proline Metabolism SMP00020 map00330 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.000012 +/- 0.000006 uM Adult (>18 years old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
1.05 +/- 0.01 uM Adult (>18 years old) Male Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
8.66 +/- 1.07 uM Newborn (0-30 days old) Not Specified Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Cerebrospinal Fluid (CSF) Detected and Quantified 8.60 +/- 0.49 uM Newborn (0-30 days old) Not Specified Hypoxic-Ischamic Encephalopathy
Cerebrospinal Fluid (CSF) Detected and Quantified 0.99 +/- 0.01 uM Adult (>18 years old) Male Subarachnoid emorrhage
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID Not Available
DrugBank Metabolite ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB021825
KNApSAcK ID Not Available
Chemspider ID 127983 Link_out
KEGG Compound ID C00533 Link_out
BioCyc ID NITRIC-OXIDE Link_out
BiGG ID 35273 Link_out
Wikipedia Link Nitric oxide Link_out
NuGOwiki Link HMDB03378 Link_out
Metagene Link HMDB03378 Link_out
METLIN ID 6912 Link_out
PubChem Compound 145068 Link_out
PDB ID Not Available
ChEBI ID 16480 Link_out
References
Synthesis Reference Morabito, 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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  22. Hurford WE: Current status of nitric oxide inhalation. Nihon Kyobu Shikkan Gakkai Zasshi. 1995 Dec;33 Suppl:199-204. Pubmed: 8752507 Link_out
  23. Stephens C, Fawcett TN: Nitric oxide and nursing: a review. J Clin Nurs. 2007 Jan;16(1):67-76. Pubmed: 17181668 Link_out
  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 Link_out

Enzymes
Name: Nitric oxide synthase, inducible
Reactions:
L-Arginine + NADPH + Oxygen unknown Citrulline + Nitric oxide + NADP + Water details
NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion unknown NADP + Nitric oxide + Citrulline + Water details
L-Arginine + Oxygen + NADPH + Hydrogen Ion unknown Nitric oxide + Citrulline + NADP + Water details
Gene Name: NOS2
Uniprot ID: P35228 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Nitric oxide synthase, brain
Reactions:
L-Arginine + NADPH + Oxygen unknown Citrulline + Nitric oxide + NADP + Water details
NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion unknown NADP + Nitric oxide + Citrulline + Water details
L-Arginine + Oxygen + NADPH + Hydrogen Ion unknown Nitric oxide + Citrulline + NADP + Water details
Gene Name: NOS1
Uniprot ID: P29475 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Nitric oxide synthase, endothelial
Reactions:
L-Arginine + NADPH + Oxygen unknown Citrulline + Nitric oxide + NADP + Water details
NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion unknown NADP + Nitric oxide + Citrulline + Water details
L-Arginine + Oxygen + NADPH + Hydrogen Ion unknown Nitric oxide + Citrulline + NADP + Water details
Gene Name: NOS3
Uniprot ID: P29474 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Hemoglobin subunit beta
Reactions: Not Available
Gene Name: HBB
Uniprot ID: P68871 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Endothelin-1
Reactions: Not Available
Gene Name: EDN1
Uniprot ID: P05305 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: NOS1 mutant
Reactions: Not Available
Gene Name: NOS1
Uniprot ID: B3VK56 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Dynein light chain 1, cytoplasmic
Reactions: Not Available
Gene Name: DYNLL1
Uniprot ID: P63167 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA