Human Metabolome Database Version 3.5

Showing metabocard for Prostaglandin H2 (HMDB01381)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-05-29 13:31:24 -0600
HMDB ID HMDB01381
Secondary Accession Numbers None
Metabolite Identification
Common Name Prostaglandin H2
Description Prostaglandin 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 Link_out, 15650407 Link_out, 16968946 Link_out)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 | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C20H32O5
Average Molecular Weight 352.4651
Monoisotopic Molecular Weight 352.224974134
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 IUPAC Name prostaglandin H2
CAS Registry Number 42935-17-1
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 Key YIBNHAJFJUQSRA-YNNPMVKQSA-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
  • Ortho Dioxane
  • Ortho Dioxolane
  • Secondary Alcohol
Direct Parent Prostaglandins and related compounds
Ontology
Status Expected 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
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 0.034 g/L ALOGPS
LogP 4.27 ALOGPS
LogP 3.96 ChemAxon
LogS -4.02 ALOGPS
pKa (strongest acidic) 4.36 ChemAxon
pKa (strongest basic) -1.6 ChemAxon
Hydrogen Acceptor Count 5 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 75.99 A2 ChemAxon
Rotatable Bond Count 12 ChemAxon
Refractivity 98.04 ChemAxon
Polarizability 39.9 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
  • Endoplasmic reticulum
Biofluid Locations Not Available
Tissue Location
  • Platelet
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
DrugBank Metabolite ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB022592
KNApSAcK ID Not Available
Chemspider ID 392800 Link_out
KEGG Compound ID C00427 Link_out
BioCyc ID PROSTAGLANDIN-H2 Link_out
BiGG ID 34952 Link_out
Wikipedia Link Prostaglandin H2 Link_out
NuGOwiki Link HMDB01381 Link_out
Metagene Link HMDB01381 Link_out
METLIN ID 3495 Link_out
PubChem Compound 445049 Link_out
PDB ID Not Available
ChEBI ID 15554 Link_out
References
Synthesis Reference Not 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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  20. Salomon RG: Levuglandins and isolevuglandins: stealthy toxins of oxidative injury. Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):185-201. Pubmed: 15650407 Link_out
  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 Link_out

Enzymes
Name: Prostaglandin E synthase
Reactions:
Prostaglandin H2 unknown Prostaglandin E2 details
Gene Name: PTGES
Uniprot ID: O14684 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Prostaglandin G/H synthase 2
Reactions:
Prostaglandin H2 + Acceptor + Water unknown Prostaglandin G2 + Reduced acceptor details
Gene Name: PTGS2
Uniprot ID: P35354 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Prostaglandin G/H synthase 1
Reactions:
Prostaglandin H2 + Acceptor + Water unknown Prostaglandin G2 + Reduced acceptor details
Gene Name: PTGS1
Uniprot ID: P23219 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Prostacyclin synthase
Reactions:
Prostaglandin H2 unknown Prostaglandin I2 details
Gene Name: PTGIS
Uniprot ID: Q16647 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Hematopoietic prostaglandin D synthase
Reactions:
Prostaglandin H2 unknown Prostaglandin D2 details
Gene Name: HPGDS
Uniprot ID: O60760 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Prostaglandin-H2 D-isomerase
Reactions:
Prostaglandin H2 unknown Prostaglandin D2 details
Gene Name: PTGDS
Uniprot ID: P41222 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Thromboxane-A synthase
Reactions:
Prostaglandin H2 unknown Thromboxane A2 details
Gene Name: TBXAS1
Uniprot ID: P24557 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Prostaglandin E synthase 2
Reactions:
Prostaglandin H2 unknown Prostaglandin E2 details
Gene Name: PTGES2
Uniprot ID: Q9H7Z7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: HCG14925, isoform CRA_a
Reactions: Not Available
Gene Name: Not Available
Uniprot ID: Q53F23 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Prostaglandin E synthase 3
Reactions:
Prostaglandin H2 unknown Prostaglandin E2 details
Gene Name: PTGES3
Uniprot ID: Q15185 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA