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Human Metabolome Database Version 3.5

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Showing metabocard for Prostaglandin I2 (HMDB01335)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:10:21 -0700
HMDB ID HMDB01335
Secondary Accession Numbers None
Metabolite Identification
Common Name Prostaglandin I2
Description Prostaglandin 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. (5Z,13E)-(15S)-6,9-alpha-epoxy-11-alpha,15-dihydroxyprosta-5,13-dienoate
  2. (5Z,13E)-(15S)-6,9-alpha-epoxy-11-alpha,15-dihydroxyprosta-5,13-dienoic acid
  3. (5Z,13E)-(15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dienoate
  4. (5Z,13E)-(15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dienoic acid
  5. (5Z,13E)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
  6. (5Z,13E)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoic acid
  7. (5Z,13E,15S)-6,9a-epoxy-11a,15-dihydroxyprosta-5,13-dienoate
  8. (5Z,13E,15S)-6,9a-epoxy-11a,15-dihydroxyprosta-5,13-dienoic acid
  9. (5Z,9a,11a,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oate
  10. (5Z,9a,11a,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid
  11. (5Z,9alpha,11alpha,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oate
  12. (5Z,9alpha,11alpha,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid
  13. Epoprostenol
  14. PGI2
  15. PGX
  16. Prostacyclin
  17. Prostacycline
  18. Prostaglandin I2
  19. Prostaglandin X
  20. Vasocyclin
Chemical Formula C20H32O5
Average Molecular Weight 352.4651
Monoisotopic Molecular Weight 352.224974134
IUPAC Name 5-[(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 IUPAC Name 5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid
CAS Registry Number 35121-78-9
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 Key KAQKFAOMNZTLHT-OZUDYXHBSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Lipids
Class Eicosanoids
Sub Class Prostaglandins and related compounds
Other Descriptors
  • Aliphatic Heteropolycyclic Compounds
  • Heterocyclic Fatty Acids
  • Organic Compounds
  • Unsaturated Fatty Acids
Substituents
  • Allyl Alcohol
  • Carboxylic Acid
  • Cyclic Alcohol
  • Enol Ether
  • Oxolane
  • Secondary Alcohol
Direct Parent Prostaglandins and related compounds
Ontology
Status Expected and 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
State Solid
Experimental Properties
Property Value Reference
Melting Point Not Available Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 0.14 g/L ALOGPS
LogP 3.83 ALOGPS
LogP 2.42 ChemAxon
LogS -3.41 ALOGPS
pKa (strongest acidic) 4.43 ChemAxon
pKa (strongest basic) -1.6 ChemAxon
Hydrogen Acceptor Count 5 ChemAxon
Hydrogen Donor Count 3 ChemAxon
Polar Surface Area 86.99 A2 ChemAxon
Rotatable Bond Count 10 ChemAxon
Refractivity 99.01 ChemAxon
Polarizability 41.47 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Biofluid Locations Not Available
Tissue Location
  • Bladder
  • Fibroblasts
  • Placenta
  • Kidney
  • Liver
  • Brain
  • Adipose Tissue
  • Nerve Cells
  • Platelet
  • Blood
Pathways
Name SMPDB Link KEGG Link
Arachidonic Acid Metabolism SMP00075 map00590 Link_out
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB022560
KNApSAcK ID Not Available
Chemspider ID 4445566 Link_out
KEGG Compound ID C01312 Link_out
BioCyc ID 5Z13E-15S-69-ALPHA-EPOXY-11-ALPHA Link_out
BiGG ID 37333 Link_out
Wikipedia Link Epoprostenol Link_out
NuGOwiki Link HMDB01335 Link_out
Metagene Link HMDB01335 Link_out
METLIN ID 778 Link_out
PubChem Compound 5282411 Link_out
PDB ID Not Available
ChEBI ID 15552 Link_out
References
Synthesis Reference Not 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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  16. Axelrod L: Insulin, prostaglandins, and the pathogenesis of hypertension. Diabetes. 1991 Oct;40(10):1223-7. Pubmed: 1936584 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
Enzymes
Name: Prostaglandin G/H synthase 2
Reactions:
  • arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O [RN:R01599]
Gene Name: PTGS2
Uniprot ID: P35354 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Prostacyclin synthase
Reactions:
  • (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13- dienoate = (5Z,13E)-(15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13- dienoate [RN:R02267]
Gene Name: PTGIS
Uniprot ID: Q16647 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Prostacyclin receptor
Reactions:
    Gene Name: PTGIR
    Uniprot ID: P43119 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA