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Showing metabocard for Prostaglandin I2 (HMDB01335)

IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (3) Show 3 proteinsXML
enzymes (3) Show 3 proteins
Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-03-02 21:26:30 UTC
HMDB IDHMDB01335
Secondary Accession NumbersNone
Metabolite Identification
Common NameProstaglandin I2
DescriptionProstaglandin I2 or prostacyclin (or PGI2) is a member of the family of lipid molecules known as eicosanoids. It is produced in endothelial cells from prostaglandin H2 (PGH2) by the action of the enzyme prostacyclin synthase. It is a powerful vasodilator and inhibits platelet aggregation. Prostaglandin I2 is the main prostaglandin synthesized by the blood vessel wall. This suggests that it may play an important role in limiting platelet-mediated thrombosis. In particular, prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). The sodium salt (known as epoprostenol) has been used to treat primary pulmonary hypertension. Prostacyclin (PGI2) is released by healthy endothelial cells and performs its function through a paracrine signaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells. The platelet Gs protein-coupled receptor (prostacyclin receptor) is activated when it binds to PGI2. This activation, in turn, signals adenylyl cyclase to produce cAMP. cAMP goes on to inhibit any undue platelet activation (in order to promote circulation) and also counteracts any increase in cytosolic calcium levels which would result from thromboxane A2 (TXA2) binding (leading to platelet activation and subsequent coagulation). PGI2 also binds to endothelial prostacyclin receptors and in the same manner raise cAMP levels in the cytosol. This cAMP then goes on to activate protein kinase A (PKA). PKA then continues the cascade by inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as antagonists. PGI2 is stable in basic buffers (pH=8), but it is rapidly hydrolyzed to 6-keto PGF1alpha in neutral or acidic solutions. The half-life is short both in vivo and in vitro, ranging from 30 seconds to a few minutes. PGI2 is administered by continuous infusion in humans for the treatment of idiopathic pulmonary hypertension.Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.
Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
(5Z,13E)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoateChEBI
(5Z,9alpha,11alpha,13E,15S)-6,9-Epoxy-11,15-dihydroxyprosta-5,13-dien-1-Oic acidChEBI
EpoprostenolChEBI
FlolanChEBI
PGI2ChEBI
PGXChEBI
ProstacyclinChEBI
Prostaglandin XChEBI
VasocyclinChEBI
(5Z,13E)-(15S)-6,9a-Epoxy-11a,15-dihydroxyprosta-5,13-dienoateGenerator
(5Z,13E)-(15S)-6,9a-Epoxy-11a,15-dihydroxyprosta-5,13-dienoic acidGenerator
(5Z,13E)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoic acidGenerator
(5Z,13E)-(15S)-6,9α-epoxy-11α,15-dihydroxyprosta-5,13-dienoateGenerator
(5Z,13E)-(15S)-6,9α-epoxy-11α,15-dihydroxyprosta-5,13-dienoic acidGenerator
(5Z,9a,11a,13E,15S)-6,9-Epoxy-11,15-dihydroxyprosta-5,13-dien-1-OateGenerator
(5Z,9a,11a,13E,15S)-6,9-Epoxy-11,15-dihydroxyprosta-5,13-dien-1-Oic acidGenerator
(5Z,9alpha,11alpha,13E,15S)-6,9-Epoxy-11,15-dihydroxyprosta-5,13-dien-1-OateGenerator
(5Z,9α,11α,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-OateGenerator
(5Z,9α,11α,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-Oic acidGenerator
(5Z,13E)-(15S)-6,9-alpha-Epoxy-11-alpha,15-dihydroxyprosta-5,13-dienoateHMDB
(5Z,13E)-(15S)-6,9-alpha-Epoxy-11-alpha,15-dihydroxyprosta-5,13-dienoic acidHMDB
(5Z,13E)-(15S)-6,9-Epoxy-11,15-dihydroxyprosta-5,13-dienoateHMDB
(5Z,13E)-(15S)-6,9-Epoxy-11,15-dihydroxyprosta-5,13-dienoic acidHMDB
(5Z,13E,15S)-6,9a-Epoxy-11a,15-dihydroxyprosta-5,13-dienoateHMDB
(5Z,13E,15S)-6,9a-Epoxy-11a,15-dihydroxyprosta-5,13-dienoic acidHMDB
ProstacyclineHMDB
EpoprostanolMeSH
Epoprostenol sodiumMeSH
Epoprostenol sodium salt, (5Z,9alpha,11alpha,13E,15S)-isomerMeSH
Prostaglandin I(2)MeSH
Chemical FormulaC20H32O5
Average Molecular Weight352.4651
Monoisotopic Molecular Weight352.224974134
IUPAC Name5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoic acid
Traditional Nameepoprostenol
CAS Registry Number35121-78-9
SMILES
CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@@H]2OC(C[C@H]12)=CCCCC(O)=O
InChI Identifier
InChI=1S/C20H32O5/c1-2-3-4-7-14(21)10-11-16-17-12-15(8-5-6-9-20(23)24)25-19(17)13-18(16)22/h8,10-11,14,16-19,21-22H,2-7,9,12-13H2,1H3,(H,23,24)/b11-10+,15-8-/t14-,16+,17+,18+,19-/m0/s1
InChI KeyKAQKFAOMNZTLHT-OZUDYXHBSA-N
Chemical Taxonomy
ClassificationNot classified
Ontology
StatusExpected but not Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.14 mg/mLALOGPS
logP3.83ALOGPS
logP2.42ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)4.43ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area86.99 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity99.01 m3·mol-1ChemAxon
Polarizability41.47 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Biofluid LocationsNot Available
Tissue Location
  • Adipose Tissue
  • Bladder
  • Blood
  • Brain
  • Fibroblasts
  • Kidney
  • Liver
  • Nerve Cells
  • Placenta
  • Platelet
Pathways
NameSMPDB LinkKEGG Link
Acetaminophen Action PathwaySMP00710Not Available
Acetylsalicylic Acid PathwaySMP00083Not Available
Antipyrine Action PathwaySMP00692Not Available
Antrafenine Action PathwaySMP00693Not Available
Arachidonic Acid MetabolismSMP00075map00590
Bromfenac PathwaySMP00102Not Available
Carprofen Action PathwaySMP00694Not Available
Celecoxib PathwaySMP00096Not Available
Diclofenac PathwaySMP00093Not Available
Diflunisal PathwaySMP00289Not Available
Etodolac PathwaySMP00084Not Available
Etoricoxib Action PathwaySMP00695Not Available
Fenoprofen Action PathwaySMP00696Not Available
Flurbiprofen Action PathwaySMP00697Not Available
Ibuprofen PathwaySMP00086Not Available
Indomethacin PathwaySMP00104Not Available
Intracellular Signalling Through Prostacyclin Receptor and ProstacyclinSMP00354Not Available
Ketoprofen PathwaySMP00085Not Available
Ketorolac PathwaySMP00098Not Available
Leukotriene C4 Synthesis DeficiencySMP00353Not Available
Lornoxicam Action PathwaySMP00700Not Available
Lumiracoxib Action PathwaySMP00699Not Available
Magnesium salicylate Action PathwaySMP00698Not Available
Mefanamic Acid PathwaySMP00109Not Available
Meloxicam PathwaySMP00106Not Available
Nabumetone PathwaySMP00114Not Available
Naproxen PathwaySMP00120Not Available
Nepafenac Action PathwaySMP00702Not Available
Oxaprozin PathwaySMP00113Not Available
Phenylbutazone Action PathwaySMP00701Not Available
Piroxicam PathwaySMP00077Not Available
Rofecoxib PathwaySMP00087Not Available
Salicylate-sodium Action PathwaySMP00708Not Available
Salicylic Acid Action PathwaySMP00709Not Available
Salsalate Action PathwaySMP00707Not Available
Sulindac PathwaySMP00094Not Available
Suprofen PathwaySMP00101Not Available
Tenoxicam Action PathwaySMP00706Not Available
Tiaprofenic Acid Action PathwaySMP00705Not Available
Tolmetin Action PathwaySMP00704Not Available
Trisalicylate-choline Action PathwaySMP00703Not Available
Valdecoxib PathwaySMP00116Not Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022560
KNApSAcK IDNot Available
Chemspider ID4445566
KEGG Compound IDC01312
BioCyc ID5Z13E-15S-69-ALPHA-EPOXY-11-ALPHA
BiGG ID37333
Wikipedia LinkEpoprostenol
NuGOwiki LinkHMDB01335
Metagene LinkHMDB01335
METLIN ID778
PubChem Compound5282411
PDB IDNot Available
ChEBI ID15552
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Walsh SW, Wang Y, Killian A: AA-2414, an antioxidant and thromboxane receptor blocker, completely inhibits peroxide-induced vasoconstriction in the human placenta. J Pharmacol Exp Ther. 1999 Jul;290(1):220-6. [PubMed:10381779 ]
  2. Brinkmann A, Seeling W, Wolf CF, Kneitinger E, Junger S, Rockemann M, Oettinger W, Georgieff M: [The effect of thoracic epidural anesthesia on the pathophysiology of the eventration syndrome]. Anaesthesist. 1994 Apr;43(4):235-44. [PubMed:8179173 ]
  3. Kearney D, Byrne A, Crean P, Cox D, Fitzgerald DJ: Optimal suppression of thromboxane A(2) formation by aspirin during percutaneous transluminal coronary angioplasty: no additional effect of a selective cyclooxygenase-2 inhibitor. J Am Coll Cardiol. 2004 Feb 18;43(4):526-31. [PubMed:14975458 ]
  4. De La Cruz JP, Arrebola MM, Villalobos MA, Pinacho A, Guerrero A, Gonzalez-Correa JA, Sanchez de la Cuesta F: Influence of glucose concentration on the effects of aspirin, ticlopidine and clopidogrel on platelet function and platelet-subendothelium interaction. Eur J Pharmacol. 2004 Jan 19;484(1):19-27. [PubMed:14729378 ]
  5. Cruz-Gervis R, Stecenko AA, Dworski R, Lane KB, Loyd JE, Pierson R, King G, Brigham KL: Altered prostanoid production by fibroblasts cultured from the lungs of human subjects with idiopathic pulmonary fibrosis. Respir Res. 2002;3:17. Epub 2002 Feb 23. [PubMed:11980586 ]
  6. den Dekker E, Gorter G, Heemskerk JW, Akkerman JW: Development of platelet inhibition by cAMP during megakaryocytopoiesis. J Biol Chem. 2002 Aug 9;277(32):29321-9. Epub 2002 May 7. [PubMed:11997386 ]
  7. McAdam BF, Byrne D, Morrow JD, Oates JA: Contribution of cyclooxygenase-2 to elevated biosynthesis of thromboxane A2 and prostacyclin in cigarette smokers. Circulation. 2005 Aug 16;112(7):1024-9. Epub 2005 Aug 8. [PubMed:16087791 ]
  8. Hei ZQ, Huang HQ, Luo CF, Li SR, Luo GJ: Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in cirrhotic patients undergoing liver transplantation. World J Gastroenterol. 2006 Jul 7;12(25):4049-51. [PubMed:16810757 ]
  9. Nadar S, Lip GY: Platelet activation in the hypertensive disorders of pregnancy. Expert Opin Investig Drugs. 2004 May;13(5):523-9. [PubMed:15155127 ]
  10. Fruzzetti F, Giannessi D, Ricci C, Bernini W, Puntoni R, Genazzani AR, De Caterina R: Platelet-vessel wall interactions with third-generation oral contraceptives: no evidence of detrimental effects. Thromb Haemost. 1999 Sep;82(3):1164-70. [PubMed:10494782 ]
  11. Cheng Y, Austin SC, Rocca B, Koller BH, Coffman TM, Grosser T, Lawson JA, FitzGerald GA: Role of prostacyclin in the cardiovascular response to thromboxane A2. Science. 2002 Apr 19;296(5567):539-41. [PubMed:11964481 ]
  12. Okamoto M, Abe T, Shouno M, Kitabata Y, Narukawa N, Kobata H, Akizawa T: A case of thrombotic thrombocytopenic purpura refractory to plasma exchange. Ther Apher. 2001 Feb;5(1):49-53. [PubMed:11258611 ]
  13. Li J, Dai G, Feng Z, Wang C, Yang Y, Wei W, Zhou B: Effect of low HDL combined with hypertriglyceridemia in coronary artery disease patients on PGI2 biological activity in relation to lipid regulating treatment. J Tongji Med Univ. 1998;18(2):87-9, 93. [PubMed:10806831 ]
  14. Vassaux G, Gaillard D, Darimont C, Ailhaud G, Negrel R: Differential response of preadipocytes and adipocytes to prostacyclin and prostaglandin E2: physiological implications. Endocrinology. 1992 Nov;131(5):2393-8. [PubMed:1330499 ]
  15. Haraldsson A, Kieler-Jensen N, Wadenvik H, Ricksten SE: Inhaled prostacyclin and platelet function after cardiac surgery and cardiopulmonary bypass. Intensive Care Med. 2000 Feb;26(2):188-94. [PubMed:10784307 ]
  16. Axelrod L: Insulin, prostaglandins, and the pathogenesis of hypertension. Diabetes. 1991 Oct;40(10):1223-7. [PubMed:1936584 ]
  17. Lehmann C, Taymoorian K, Wauer H, Krausch D, Birnbaum J, Kox WJ: Effects of the stable prostacyclin analogue iloprost on the plasma disappearance rate of indocyanine green in human septic shock. Intensive Care Med. 2000 Oct;26(10):1557-60. [PubMed:11126272 ]
  18. Dickinson JE, Meyer BA, Brath PC, Chmielowiec S, Walsh SW, Parisi VM, Palmer SM: Placental thromboxane and prostacyclin production in an ovine diabetic model. Am J Obstet Gynecol. 1990 Dec;163(6 Pt 1):1831-5. [PubMed:2147814 ]
  19. Watanabe T, Kishi Y, Numano F, Isobe M: Enhanced platelet sensitivity to prostacyclin in patients in an active stage of Takayasu arteritis. Thromb Res. 2001 Oct 15;104(2):77-83. [PubMed:11672751 ]
  20. Harada N, Okajima K, Yuksel M, Isobe H: Contribution of capsaicin-sensitive sensory neurons to antithrombin-induced reduction of ischemia/reperfusion-induced liver injury in rats. Thromb Haemost. 2005 Jan;93(1):48-56. [PubMed:15630490 ]

Enzymes

Enzyme Details
1. Prostaglandin G/H synthase 2
General function:
Involved in peroxidase activity
Specific function:
Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular weight:
68995.625
Enzyme Details
2. Prostacyclin synthase
General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).
Gene Name:
PTGIS
Uniprot ID:
Q16647
Molecular weight:
57103.385
Reactions
Prostaglandin H2 → Prostaglandin I2details
Enzyme Details
3. Prostacyclin receptor
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase
Gene Name:
PTGIR
Uniprot ID:
P43119
Molecular weight:
40955.5