General Information of MET (ID: META00092)
Name Prostaglandin E2
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(-)-Prostaglandin e2; (15S)-Prostaglandin e2; (5Z,11a,13E,15S)-11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-Oate; (5Z,11a,13E,15S)-11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-Oic acid; (5Z,11alpha,13E,15S)-11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-Oic acid; (5Z,13E)-(15S)-11a,15-Dihydroxy-9-oxoprost-13-enoate; (5Z,13E)-(15S)-11a,15-Dihydroxy-9-oxoprost-13-enoic acid; (5Z,13E)-(15S)-11a,15-Dihydroxy-9-oxoprosta-5,13-dienoate; (5Z,13E)-(15S)-11a,15-Dihydroxy-9-oxoprosta-5,13-dienoic acid; (5Z,13E)-(15S)-11alpha,15-Dihydroxy-9-oxoprost-13-enoate; (5Z,13E)-(15S)-11alpha,15-Dihydroxy-9-oxoprosta-5,13-dienoate; (5Z,13E,15S)-11-alpha,15-Dihydroxy-9-oxoprost-5,13-dienoate; (5Z,13E,15S)-11-alpha,15-Dihydroxy-9-oxoprost-5,13-dienoic acid; (Z)-7-((1R,2R,3R)-3-Hydroxy-2-((S,e)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoate; (Z)-7-((1R,2R,3R)-3-Hydroxy-2-((S,e)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoic acid; (e,Z)-(1R,2R,3R)-7-(3-Hydroxy-2-((3S)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoate; (e,Z)-(1R,2R,3R)-7-(3-Hydroxy-2-((3S)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoic acid; 5-trans-PGE2; Cervidil; Dinoproston; Dinoprostona; Dinoprostone; Dinoprostonum; Gel, prepidil; Glandin; L-Prostaglandin e2; Minprositin e2; Minprostin e2; PGE2; PGE2 alpha; PGE2alpha; Prepidil; Prepidil gel; Propess; Prostaglandin e; Prostaglandin e2 alpha; Prostaglandin e2alpha; Prostarmon e; Prostenon; Prostin; Prostin e2; alpha, PGE2; alpha, Prostaglandin e2; e2 alpha, Prostaglandin; e2, Prostaglandin; e2alpha, Prostaglandin
Source Endogenous;Escherichia Coli Metabolite;Fatty acyls;Food;Drug
Structure Type   Eicosanoids  (Click to Show/Hide the Complete Structure Type Hierarchy)
Lipids and lipid-like molecules
Fatty Acyls
Eicosanoids
PubChem CID
5280360
HMDB ID
HMDB0001220
Formula
C20H32O5
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C00584
DrugBank ID
DB00917
ChEBI ID
15551
FooDB ID
FDB022498
ChemSpider ID
4444059
METLIN ID
6089
Physicochemical Properties Molecular Weight 352.5 Topological Polar Surface Area 94.8
XlogP 2.8 Complexity 469
Heavy Atom Count 25 Rotatable Bond Count 12
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 5
Function
The naturally occurring prostaglandin E2 (PGE2) is known in medicine as dinoprostone, and it is the most common and most biologically active of the mammalian prostaglandins. It has important effects during labour and also stimulates osteoblasts to release factors which stimulate bone resorption by osteoclasts (a type of bone cell that removes bone tissue by removing the bone's mineralized matrix). PGE2 is also the prostaglandin that ultimately induces fever. PGE2 has been shown to increase vasodilation and cAMP production, enhance the effects of bradykinin and histamine, and induce uterine contractions and platelet aggregation. PGE2 is also responsible for maintaining the open passageway of the fetal ductus arteriosus, decreasing T-cell proliferation and lymphocyte migration, and activating the secretion of IL-1 and IL-2. PGE2 exhibits both pro- and anti-inflammatory effects, particularly on dendritic cells (DC). Depending on the nature of maturation signals, PGE2 has different and sometimes opposite effects on DC biology. PGE2 exerts an inhibitory action, reducing the maturation of DC and their ability to present antigen. PGE2 has also been shown to stimulate DC and promote IL-12 production when given in combination with TNF-alpha. PGE2 is an environmentally bioactive substance. Its action is prolonged and sustained by other factors especially IL-10. It modulates the activities of professional DC by acting on their differentiation, maturation, and their ability to secrete cytokines. PGE2 is a potent inducer of IL-10 in bone marrow-derived DC (BM-DC). PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype. 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 and are 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 signalling pathways.
Regulatory Network
Full List of Protein(s) Regulated by This Metabolite
      Voltage-gated ion channel (VIC)
            Cation channel sperm-associated 1 (CatSper1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Prostaglandin E2 addition (6 hours)
                      Induced Change CATSPER1 protein activity levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that prostaglandin E2 addition causes the increase of CATSPER1 protein activity compared with control group.
            Cation channel sperm-associated 2 (CatSper2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Prostaglandin E2 addition (6 hours)
                      Induced Change CATSPER2 protein activity levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that prostaglandin E2 addition causes the increase of CATSPER2 protein activity compared with control group.
            Cation channel sperm-associated 3 (CatSper3) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Prostaglandin E2 addition (6 hours)
                      Induced Change CATSPER3 protein activity levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that prostaglandin E2 addition causes the increase of CATSPER3 protein activity compared with control group.
            Cation channel sperm-associated 4 (CATSPER4) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Prostaglandin E2 addition (6 hours)
                      Induced Change CATSPER4 protein activity levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that prostaglandin E2 addition causes the increase of CATSPER4 protein activity compared with control group.
Full List of Protein(s) Regulating This Metabolite
      Hydrolases (EC 3)
            Group 10 secretory phospholipase A2 (PLA2G10) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Overexpression of Pla2g10
                      Induced Change Prostaglandin E2 concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Inflammatory bowel disease [ICD-11: DD72]
                      Details It is reported that overexpression of Pla2g10 leads to the increase of prostaglandin E2 levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Knockout of Pla2g10
                      Induced Change Prostaglandin E2 concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Acute asthma exacerbations [ICD-11: CA23]
                      Details It is reported that knockout of Pla2g10 leads to the decrease of prostaglandin E2 levels compared with control group.
            Group 3 secretory phospholipase A2 (PLA2G3) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Knockout of Pla2g3
                      Induced Change Prostaglandin E2 concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Colorectal cancer [ICD-11: 2B91]
                      Details It is reported that knockout of Pla2g3 leads to the increase of prostaglandin E2 levels compared with control group.
            Monoacylglycerol lipase ABHD6 (ABHD6) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Inhibition (WWL70) of Abhd6
                      Induced Change Prostaglandin E2 concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of Abhd6 leads to the decrease of prostaglandin E2 levels compared with control group.
            Sulfatase sulf-1 (SULF1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [6]
                      Introduced Variation Knockdown (shRNA) of SULF1
                      Induced Change Prostaglandin E2 concentration: decrease (FC = 0.19 / 0.19)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Ovarian cancer [ICD-11: 2C73]
                      Details It is reported that knockdown of SULF1 leads to the decrease of prostaglandin E2 levels compared with control group.
      Organo anion transporter (OAT)
            Organic anion transporter D (SLCO3A1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Overexpression of SLCO3A1
                      Induced Change Prostaglandin E2 concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLCO3A1 leads to the increase of prostaglandin E2 levels compared with control group.
            Organic anion transporter E (SLCO4A1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Overexpression of SLCO4A1
                      Induced Change Prostaglandin E2 concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLCO4A1 leads to the increase of prostaglandin E2 levels compared with control group.
            Solute carrier SLCO1B1 (OATP-C) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Overexpression of SLCO1B1
                      Induced Change Prostaglandin E2 concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLCO1B1 leads to the increase of prostaglandin E2 levels compared with control group.
            Solute carrier SLCO2B1 (OATPB) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [7]
                      Introduced Variation Overexpression of SLCO2B1
                      Induced Change Prostaglandin E2 concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLCO2B1 leads to the increase of prostaglandin E2 levels compared with control group.
References
1 Progesterone activates the principal Ca2+ channel of human sperm. Nature. 2011 Mar 17;471(7338):387-91.
2 Group X Secreted Phospholipase A2 Releases 3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility. J Biol Chem. 2016 Mar 25;291(13):6895-911.
3 Importance of group X-secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model. J Exp Med. 2007 Apr 16;204(4):865-77.
4 Group III phospholipase A 2 promotes colitis and colorectal cancer. Sci Rep. 2017 Sep 25;7(1):12261.
5 Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17558-63.
6 Erratum to: Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer. Cancer Metab. 2014 Nov 4;2:24.
7 Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60.

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