You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2006-05-22 15:12:43 UTC
Update Date2016-02-11 01:06:08 UTC
HMDB IDHMDB03235
Secondary Accession Numbers
  • HMDB05100
Metabolite Identification
Common NameProstaglandin G2
DescriptionProstaglandin G2 (PGG2) is synthesized from arachidonic acid on a cyclooxygenase (COX) metabolic pathway as a primary step; the COX biosynthesis of prostaglandin (PG) begins with the highly specific oxygenation of arachidonic acid in the 11R configuration and ends with a 15S oxygenation to form PGG2. The COX site activity that catalyzes the conversion of arachidonic acid to PGG2 is the target for nonsteroidal antiinflammatory drugs (NSAIDs). The peroxidase site activity catalyzes the two-electron reduction of the hydroperoxide bond of PGG2 to yield the corresponding alcohol prostaglandin H2 (PGH2). The formation of a phenoxyl radical on Tyr385 couples the activities of the two sites. The Tyr385 radical is produced via oxidation by compound I, an oxoferryl porphyrin -cation radical, which is generated by reaction of the hemin resting state with PGG2 or other hydroperoxides. The tyrosyl radical homolytically abstracts the 13proS hydrogen atom of arachidonic acid which initiates a radical cascade that ends with the stereoselective formation of PGG2. PGG2 then migrates from the cyclooxygenase (COX) site to the peroxidase (POX) site where it reacts with the hemin group to generate PGH2 and compound I. The heterolytic oxygen-oxygen bond cleavage is assisted by the conserved distal residues His207 and Gln203, mutation of which has been shown to severely impair enzyme activity. Compound I, upon reaction with Tyr385, gives compound II, which in turn is reduced to the hemin resting state by one-electron oxidation of reducing cosubstrates or undergoes reactions that result in enzyme self-inactivation. Prostaglandin endoperoxide H synthase (PGHS) 1 is a bifunctional membrane enzyme of the endoplasmic reticulum that converts arachidonic acid into prostaglandin H2 (PGH2), the precursor of all prostaglandins, thromboxanes, and prostacyclins. These lipid mediators are intricately involved in normal physiology, namely, in mitogenesis, fever generation, pain response, lymphocyte chemotaxis, fertility, and contradictory stimuli such as vasoconstriction and vasodilatation, as well as platelet aggregation and quiescence. PGHS is implicated in numerous pathologies, including inflammation, cancers of the colon, lung, and breast, Alzheimer's disease, Parkinson's disease, and numerous cardiovascular diseases including atherosclerosis, thrombosis, myocardial infarction, and stroke. (PMID: 14594816 , 16552393 , 16411757 ). 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
ValueSource
PGG2ChEBI
(5Z)-7-{(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroperoxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]hept-5-yl}hept-5-enoateHMDB
(5Z)-7-{(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroperoxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]hept-5-yl}hept-5-enoic acidHMDB
9,11-Epidioxy-15-hydroperoxy-prosta-5,13-dien-1-OateHMDB
9,11-Epidioxy-15-hydroperoxy-prosta-5,13-dien-1-Oic acidHMDB
9S,11R-Epidioxy-15S-hydroperoxy-5Z,13E-prostadienoateHMDB
9S,11R-Epidioxy-15S-hydroperoxy-5Z,13E-prostadienoic acidHMDB
Endoperoxide g2HMDB
Chemical FormulaC20H32O6
Average Molecular Weight368.4645
Monoisotopic Molecular Weight368.219888756
IUPAC Name(5Z)-7-[(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroperoxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]heptan-5-yl]hept-5-enoic acid
Traditional Nameprostaglandin G2
CAS Registry Number51982-36-6
SMILES
[H][C@@]12C[C@@]([H])(OO1)[C@H](\C=C\[C@H](CCCCC)OO)[C@H]2C\C=C/CCCC(O)=O
InChI Identifier
InChI=1S/C20H32O6/c1-2-3-6-9-15(24-23)12-13-17-16(18-14-19(17)26-25-18)10-7-4-5-8-11-20(21)22/h4,7,12-13,15-19,23H,2-3,5-6,8-11,14H2,1H3,(H,21,22)/b7-4-,13-12+/t15-,16+,17+,18-,19+/m0/s1
InChI KeyInChIKey=SGUKUZOVHSFKPH-YNNPMVKQSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassEicosanoids
Direct ParentProstaglandins and related compounds
Alternative Parents
Substituents
  • Prostaglandin skeleton
  • Long-chain fatty acid
  • Hydroperoxy fatty acid
  • Heterocyclic fatty acid
  • Fatty acid
  • Unsaturated fatty acid
  • Ortho-dioxane
  • Ortho-dioxolane
  • Dialkyl peroxide
  • Hydroperoxide
  • Oxacycle
  • Organoheterocyclic compound
  • Peroxol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
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)
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 Solubility0.026 mg/mLALOGPS
logP4.31ALOGPS
logP4.41ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)4.36ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area85.22 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity99.39 m3·mol-1ChemAxon
Polarizability40.85 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0119000000-06893304af83e030a39bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0zmr-3369000000-b1d0f67eea930b11ae4cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-1003-9400000000-7fbd48d8b1a086fc44d2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0019000000-4a1c6a9bb1b35fe201efView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00r2-2149000000-16bc14c91731cdc79586View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9162000000-ad0929ccdcab78d69a99View in MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid LocationsNot Available
Tissue LocationNot Available
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
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 IDFDB023127
KNApSAcK IDNot Available
Chemspider ID4444406
KEGG Compound IDC05956
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB03235
Metagene LinkHMDB03235
METLIN ID3508
PubChem Compound5280883
PDB IDPGX
ChEBI ID27647
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Agnoli GC, Borgatti R, Cacciari M, Dorigoni S, Garutti C, Ikonomu E, Marinelli M: [Urinary excretion of prostanoids in the course of changes in diuresis over short and long terms respectively] Boll Soc Ital Biol Sper. 1987 Apr 30;63(4):357-63. [3447615 ]
  2. Burdan F, Chalas A, Szumilo J: [Cyclooxygenase and prostanoids--biological implications]. Postepy Hig Med Dosw (Online). 2006;60:129-41. [16552393 ]
  3. Schneider C, Boeglin WE, Brash AR: Identification of two cyclooxygenase active site residues, Leucine 384 and Glycine 526, that control carbon ring cyclization in prostaglandin biosynthesis. J Biol Chem. 2004 Feb 6;279(6):4404-14. Epub 2003 Oct 31. [14594816 ]
  4. Chubb AJ, Fitzgerald DJ, Nolan KB, Moman E: The productive conformation of prostaglandin G2 at the peroxidase site of prostaglandin endoperoxide H synthase: docking, molecular dynamics, and site-directed mutagenesis studies. Biochemistry. 2006 Jan 24;45(3):811-20. [16411757 ]

Enzymes

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
Arachidonic acid + Oxygen → Prostaglandin G2details
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
Arachidonic acid + Oxygen → Prostaglandin G2details