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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-05-29 19:31:24 UTC
HMDB IDHMDB01381
Secondary Accession NumbersNone
Metabolite Identification
Common NameProstaglandin H2
DescriptionProstaglandin H2 (PGH2) is the first intermediate in the biosynthesis of all prostaglandins. Prostaglandins are synthesized from arachidonic acid by the enzyme COX-1 and COX-2, which are also called PGH synthase 1 and 2. These enzymes generate a reactive intermediate PGH2 which has a reasonably long half-life (90-100 s) but is highly lipophilic. PGH2 is converted into the biologically active prostaglandins by prostaglandin isomerases, yielding PGE2, PGD2, and PGF2, or by thromboxane synthase to make TxA2 or by prostacyclin synthase to make PGI2. Most nonsteroidal anti-inflammatory drugs such as aspirin and indomethacin inhibit both PGH synthase 1 and 2. A key feature for eicosanoid transcellular biosynthesis is the export of PGH2 or LTA4 from the donor cell as well as the uptake of these reactive intermediates by the acceptor cell. Very little is known about either process despite the demonstrated importance of both events. In cells, PGH2 rearranges nonenzymatically to LGs even in the presence of enzymes that use PGH2 as a substrate. When platelets form Thromboxane A2 (TXA2) from endogenous arachidonic acid (AA), PGH2 reaches concentrations very similar to those of TXA2 and high enough to produce strong platelet activation. Therefore, platelet activation by TXA2 appears to go along with an activation by PGH2. The agonism of PGH2 is limited by the formation of inhibitory prostaglandins, especially PGD2 at higher concentrations. That is why thromboxane synthase inhibitors in PRP and at a physiological HSA concentration do not augment platelet activation. (PMID: 2798452 , 15650407 , 16968946 )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
Synonyms
  1. (15S)Hydroxy-9alpha,11alpha-(epoxymethano)prosta-5,13-dienoate
  2. (15S)Hydroxy-9alpha,11alpha-(epoxymethano)prosta-5,13-dienoic acid
  3. (5Z)-7-{(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]hept-5-yl}hept-5-enoate
  4. (5Z)-7-{(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]hept-5-yl}hept-5-enoic acid
  5. (5Z,13E)-(15S)-9,11-epidioxy-15-hydroxyprosta-5,13-dienoate
  6. (5Z,13E)-(15S)-9,11-epidioxy-15-hydroxyprosta-5,13-dienoic acid
  7. (5Z,13E)-(15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
  8. (5Z,13E)-(15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoic acid
  9. (5Z,13E)-(15S)-9alpha,11alpha-Epidioxy-15-hydroxyprosta-5,13-dienoate
  10. (5Z,13E)-(15S)-9alpha,11alpha-Epidioxy-15-hydroxyprosta-5,13-dienoic acid
  11. (5Z,13E,15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
  12. (5Z,13E,15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoic acid
  13. (5Z,13E,15S)-9a,11a-epidioxy-15-hydroxyprosta-5,13-dienoate
  14. (5Z,13E,15S)-9a,11a-epidioxy-15-hydroxyprosta-5,13-dienoic acid
  15. (5Z,9a,11a,13E,15S)-9,11-epidioxy-15-hydroxyprosta-5,13-dien-1-oate
  16. (5Z,9a,11a,13E,15S)-9,11-epidioxy-15-hydroxyprosta-5,13-dien-1-oic acid
  17. (5Z,9alpha,11alpha,13E,15S)-9,11-epidioxy-15-hydroxy-Prosta-5,13-dien-1-oate
  18. (5Z,9alpha,11alpha,13E,15S)-9,11-epidioxy-15-hydroxy-Prosta-5,13-dien-1-oic acid
  19. 15-Hydroxy-9alpha,11alpha-peroxidoprosta-5,13-dienoate
  20. 15-Hydroxy-9alpha,11alpha-peroxidoprosta-5,13-dienoic acid
  21. 9,11-Epoxymethano-pgh2
  22. 9S,11R-Epidioxy-15S-hydroxy-5Z,13E-prostadienoate
  23. 9S,11R-Epidioxy-15S-hydroxy-5Z,13E-prostadienoic acid
  24. Endoperoxide H2
  25. PGH2
  26. Prostaglandin R2
  27. Prostaglandin-H2
Chemical FormulaC20H32O5
Average Molecular Weight352.4651
Monoisotopic Molecular Weight352.224974134
IUPAC Name(5Z)-7-[(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]heptan-5-yl]hept-5-enoic acid
Traditional Nameprostaglandin H2
CAS Registry Number42935-17-1
SMILES
CCCCC[C@H](O)\C=C\[C@H]1[C@H]2C[C@H](OO2)[C@@H]1C\C=C/CCCC(O)=O
InChI Identifier
InChI=1S/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18-14-19(17)25-24-18)10-7-4-5-8-11-20(22)23/h4,7,12-13,15-19,21H,2-3,5-6,8-11,14H2,1H3,(H,22,23)/b7-4-,13-12+/t15-,16+,17+,18-,19+/m0/s1
InChI KeyYIBNHAJFJUQSRA-YNNPMVKQSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassLipids
ClassEicosanoids
Sub ClassProstaglandins and related compounds
Other Descriptors
  • Aliphatic Heteropolycyclic Compounds
  • Heterocyclic Fatty Acids
  • Organic Compounds
  • Unsaturated Fatty Acids
Substituents
  • Allyl Alcohol
  • Carboxylic Acid
  • Ortho Dioxane
  • Ortho Dioxolane
  • Secondary Alcohol
Direct ParentProstaglandins and related compounds
Ontology
StatusExpected and Not Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Component of Prostaglandin and leukotriene metabolism
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • 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 Solubility0.034ALOGPS
logP4.27ALOGPS
logP3.96ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)4.36ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.99 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity98.04 m3·mol-1ChemAxon
Polarizability39.9 Å3ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • Endoplasmic reticulum
Biofluid LocationsNot Available
Tissue Location
  • Platelet
Pathways
NameSMPDB LinkKEGG Link
Arachidonic Acid MetabolismSMP00075map00590
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 IDFDB022592
KNApSAcK IDNot Available
Chemspider ID392800
KEGG Compound IDC00427
BioCyc IDPROSTAGLANDIN-H2
BiGG ID34952
Wikipedia LinkProstaglandin H2
NuGOwiki LinkHMDB01381
Metagene LinkHMDB01381
METLIN ID3495
PubChem Compound445049
PDB IDNot Available
ChEBI ID15554
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Onguru O, Casey MB, Kajita S, Nakamura N, Lloyd RV: Cyclooxygenase-2 and thromboxane synthase in non-endocrine and endocrine tumors: a review. Endocr Pathol. 2005 Winter;16(4):253-77. Pubmed: 16627914
  2. Rybicki JP, Le Breton GC: Prostaglandin H2 directly lowers human platelet cAMP levels. Thromb Res. 1983 Jun 1;30(5):407-14. Pubmed: 6310815
  3. Ulrich CM, Carlson CS, Sibert J, Poole EM, Yu JH, Wang LH, Sparks R, Potter JD, Bigler J: Thromboxane synthase (TBXAS1) polymorphisms in African-American and Caucasian populations: evidence for selective pressure. Hum Mutat. 2005 Oct;26(4):394-5. Pubmed: 16134166
  4. Hornberger W, Patscheke H: Transient concentrations and agonist potency of PGH2 in platelet activation by endogenous arachidonate. Eicosanoids. 1989;2(4):241-8. Pubmed: 2517034
  5. Johnson GJ, Dunlop PC, Leis LA, From AH: Dihydropyridine agonist Bay K 8644 inhibits platelet activation by competitive antagonism of thromboxane A2-prostaglandin H2 receptor. Circ Res. 1988 Mar;62(3):494-505. Pubmed: 2449295
  6. Maclouf J, Kindahl H, Granstrom E, Samuelsson B: Interactions of prostaglandin H2 and thromboxane A2 with human serum albumin. Eur J Biochem. 1980 Aug;109(2):561-6. Pubmed: 7408901
  7. Gerrard JM, White JG, Rao GH, Townsend D: Localization of platelet prostaglandin production in the platelet dense tubular system. Am J Pathol. 1976 May;83(2):283-98. Pubmed: 1266944
  8. Patscheke H, Hornberger W, Zehender H: Pathophysiological role of thromboxane A2 and pharmacological approaches to its inhibition. Z Kardiol. 1990;79 Suppl 3:151-4. Pubmed: 2099038
  9. Goerig M, Habenicht AJ, Zeh W, Salbach P, Kommerell B, Rothe DE, Nastainczyk W, Glomset JA: Evidence for coordinate, selective regulation of eicosanoid synthesis in platelet-derived growth factor-stimulated 3T3 fibroblasts and in HL-60 cells induced to differentiate into macrophages or neutrophils. J Biol Chem. 1988 Dec 25;263(36):19384-91. Pubmed: 2848824
  10. Beitz J, Forster W: Influence of human low density and high density lipoprotein cholesterol on the in vitro prostaglandin I2 synthetase activity. Biochim Biophys Acta. 1980 Dec 5;620(3):352-5. Pubmed: 6786342
  11. Mevkh AT, Basevich VV, Varfolomeev SD: [Synthesis of thromboxane A2: limiting stages of primary thrombocyte aggregation in humans initiated by arachidonic acid and its metabolic products] Biokhimiia. 1984 Dec;49(12):2035-40. Pubmed: 6441604
  12. Basevich VV, Mevkh AT, Varfolomeev SD: [Kinetic mechanisms of enzyme activity of the thromboxane synthetase system. Thromboxane synthetase of human platelets] Biokhimiia. 1984 Sep;49(9):1538-45. Pubmed: 6440597
  13. Gresele P, Deckmyn H, Nenci GG, Vermylen J: Thromboxane synthase inhibitors, thromboxane receptor antagonists and dual blockers in thrombotic disorders. Trends Pharmacol Sci. 1991 Apr;12(4):158-63. Pubmed: 1829559
  14. Borg C, Lam SC, Dieter JP, Lim CT, Komiotis D, Venton DL, Le Breton GC: Anti-peptide antibodies against the human blood platelet thromboxane A2/prostaglandin H2 receptor. Production, purification and characterization. Biochem Pharmacol. 1993 May 25;45(10):2071-8. Pubmed: 7685602
  15. Miller OV, Johnson RA, Gorman RR: Inhibition of PGE1-stimulated cAMP accumulation in human platelets by thromboxane a2. Prostaglandins. 1977 Apr;13(4):599-609. Pubmed: 193153
  16. Kuzuya T, Hoshida S, Yamagishi M, Ohmori M, Inoue M, Kamada T, Tada M: Effect of OKY-046, a thromboxane A2 synthetase inhibitor, on arachidonate-induced platelet aggregation: possible role of "prostaglandin H2 steal" mechanism. Jpn Circ J. 1986 Nov;50(11):1071-8. Pubmed: 3102802
  17. Vezza R, Mezzasoma AM, Venditti G, Gresele P: Prostaglandin endoperoxides and thromboxane A2 activate the same receptor isoforms in human platelets. Thromb Haemost. 2002 Jan;87(1):114-21. Pubmed: 11848439
  18. Ushikubi F, Nakajima M, Hirata M, Okuma M, Fujiwara M, Narumiya S: Purification of the thromboxane A2/prostaglandin H2 receptor from human blood platelets. J Biol Chem. 1989 Oct 5;264(28):16496-501. Pubmed: 2528545
  19. Hornberger WB, Patscheke H: Prostaglandin H2 in human platelet activation: coactivator and substitute for thromboxane A2. Prog Clin Biol Res. 1989;301:315-9. Pubmed: 2798452
  20. Salomon RG: Levuglandins and isolevuglandins: stealthy toxins of oxidative injury. Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):185-201. Pubmed: 15650407
  21. Folco G, Murphy RC: Eicosanoid transcellular biosynthesis: from cell-cell interactions to in vivo tissue responses. Pharmacol Rev. 2006 Sep;58(3):375-88. Pubmed: 16968946

Enzymes

General function:
Involved in prostaglandin-E synthase activity
Specific function:
Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).
Gene Name:
PTGES
Uniprot ID:
O14684
Molecular weight:
17102.135
Reactions
Prostaglandin H2 → Prostaglandin E2details
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
Reactions
Prostaglandin H2 + Acceptor + Water → Prostaglandin G2 + Reduced acceptordetails
General function:
Involved in peroxidase activity
Specific function:
May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells.
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular weight:
68685.82
Reactions
Prostaglandin H2 + Acceptor + Water → Prostaglandin G2 + Reduced acceptordetails
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
General function:
Involved in glutathione transferase activity
Specific function:
Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide.
Gene Name:
HPGDS
Uniprot ID:
O60760
Molecular weight:
23343.65
Reactions
Prostaglandin H2 → Prostaglandin D2details
General function:
Involved in binding
Specific function:
Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation. Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophopic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system.
Gene Name:
PTGDS
Uniprot ID:
P41222
Molecular weight:
21028.665
Reactions
Prostaglandin H2 → Prostaglandin D2details
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
TBXAS1
Uniprot ID:
P24557
Molecular weight:
60648.885
Reactions
Prostaglandin H2 → Thromboxane A2details
General function:
Involved in electron carrier activity
Specific function:
Isomerase that catalyzes the conversion of unstable intermediate of prostaglandin E2 H2 (PGH2) into the more stable prostaglandin E2 (PGE2) form. May also have transactivation activity toward IFN-gamma (IFNG), possibly via an interaction with CEBPB; however, the relevance of transcription activation activity remains unclear.
Gene Name:
PTGES2
Uniprot ID:
Q9H7Z7
Molecular weight:
21337.205
Reactions
Prostaglandin H2 → Prostaglandin E2details
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
Not Available
Uniprot ID:
Q53F23
Molecular weight:
60648.9
General function:
Involved in prostaglandin-E synthase activity
Specific function:
Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes.
Gene Name:
PTGES3
Uniprot ID:
Q15185
Molecular weight:
18697.195
Reactions
Prostaglandin H2 → Prostaglandin E2details