Prostaglandin synthesis and regulation (WP98)

A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are mediators and have a variety of strong physiological effects, such as regulating the contraction and relaxation of smooth muscle tissue.[1] Prostaglandins are not hormones, but autocrine or paracrine, which are locally acting messenger molecules. They differ from hormones in that they are not produced at a discrete site but in many places throughout the human body. Also, their target cells are present in the immediate vicinity of the site of their secretion (of which there are many). The prostaglandins, together with the thromboxanes and prostacyclins, form the prostanoid class of fatty acid derivatives, a subclass of eicosanoids. Adapted from [https://www.ncbi.nlm.nih.gov/pubmed/10785607 Gross, G et al. 2000, Society for Gynecologic Investigation; 7:88-95]. Description adapted from [https://en.wikipedia.org/wiki/Prostaglandin Wikipedia]. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP98 CPTAC Assay Portal]
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Authors

Nsalomonis, MaintBot, Khanspers, AlexanderPico, Mkutmon, Egonw, MirellaKalafati, Vjlynch, DeSl, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: prostaglandin metabolic pathway prostaglandin biosynthetic pathway classic metabolic pathway

Participants

Label Type Compact Identifier
Cortisone Metabolite chebi:16962
CYP11A1 GeneProduct ncbigene:1583
ANXA5 GeneProduct ncbigene:308
EDNRB GeneProduct ncbigene:1910
PGF2a Metabolite hmdb:HMDB0001139
PTGER4 GeneProduct ncbigene:5734
S100A10 GeneProduct ncbigene:6281
S100A6 GeneProduct ncbigene:6277
Calcium Metabolite hmdb:HMDB0000464
PTGFR GeneProduct ncbigene:5737
PTGIS GeneProduct ncbigene:5740
PTGER2 GeneProduct ncbigene:5732
PTGER1 GeneProduct ncbigene:5731
HPGD GeneProduct ncbigene:3248
PTGS2 GeneProduct ncbigene:5743
PGF2a Metabolite hmdb:HMDB0001139
Arachidonic Acid Metabolite cas:506-32-1
PRL GeneProduct ncbigene:5617
ANXA8 GeneProduct ncbigene:244
PLA2G4A GeneProduct ncbigene:5321
Cortisol Metabolite wikidata:Q190875
ANXA4 GeneProduct ncbigene:307
PGE2 Metabolite hmdb:HMDB0003175
SCGB1A1 GeneProduct ncbigene:7356
PTGDS GeneProduct ncbigene:5730
EDN1 GeneProduct ncbigene:1906
PGI2 Metabolite hmdb:HMDB0001335
ANXA3 GeneProduct ncbigene:306
HSD11B1 GeneProduct ncbigene:3290
Gq signalingpathway Pathway wikipathways:WP35
ANXA1 GeneProduct ncbigene:301
PTGDR GeneProduct ncbigene:5729
PTGIR GeneProduct ncbigene:5739
Calcium Metabolite hmdb:HMDB0000464
HSD11B2 GeneProduct ncbigene:3291
PTGS1 GeneProduct ncbigene:5742
Cell MembranePhospholipids Metabolite chebi:16247
TXA2 Metabolite hmdb:HMDB0001452
ANXA6 GeneProduct ncbigene:309
EDNRA GeneProduct ncbigene:1909
Cortisol Metabolite wikidata:Q190875
TBXAS1 GeneProduct ncbigene:6916
Prostaglandin H2 Metabolite cas:745-65-3
Progesterone Metabolite cas:57-83-0
PTGER3 GeneProduct ncbigene:5733
ANXA2 GeneProduct ncbigene:302
ABCC4 GeneProduct ncbigene:10257
PGD2 Metabolite kegg.compound:C00696
HPGDS GeneProduct ncbigene:27306
MITF GeneProduct ncbigene:4286
PTGES GeneProduct ncbigene:9536
PPARG GeneProduct ncbigene:5468
PPARGC1A GeneProduct ncbigene:10891
PPARGC1B GeneProduct ncbigene:133522
SOX9 GeneProduct ncbigene:6662
AKR1B GeneProduct uniprot:P15121
AKR1C3 GeneProduct ncbigene:8644
CBR1 GeneProduct ncbigene:873
AKR1C1 GeneProduct ncbigene:1645
AKR1C2 GeneProduct ncbigene:1646
AKR1C1 GeneProduct ncbigene:1645
20-dihydroprogesterone Metabolite chebi:36728
PGI2 Metabolite hmdb:HMDB0001335
PGE2 Metabolite hmdb:HMDB0003175
PGD2 Metabolite kegg.compound:C00696
TBXA2R GeneProduct ncbigene:6915
TXA2 Metabolite hmdb:HMDB0001452
PTGFRN GeneProduct ncbigene:5738

References

  1. Matsuura K, Shiraishi H, Hara A, Sato K, Deyashiki Y, Ninomiya M, et al. Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity. J Biochem. 1998 Nov;124(5):940–6. PubMed Europe PMC Scholia
  2. Gross G, Imamura T, Muglia LJ. Gene knockout mice in the study of parturition. J Soc Gynecol Investig. 2000;7(2):88–95. PubMed Europe PMC Scholia
  3. Stipp CS, Orlicky D, Hemler ME. FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein. J Biol Chem. 2001 Feb 16;276(7):4853–62. PubMed Europe PMC Scholia
  4. Jowsey IR, Thomson AM, Flanagan JU, Murdock PR, Moore GB, Meyer DJ, et al. Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. Biochem J. 2001 Nov 1;359(Pt 3):507–16. PubMed Europe PMC Scholia
  5. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, et al. The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244–9. PubMed Europe PMC Scholia
  6. Morii E, Oboki K. MITF is necessary for generation of prostaglandin D2 in mouse mast cells. J Biol Chem. 2004 Nov 19;279(47):48923–9. PubMed Europe PMC Scholia
  7. Wilhelm D, Hiramatsu R, Mizusaki H, Widjaja L, Combes AN, Kanai Y, et al. SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development. J Biol Chem. 2007 Apr 6;282(14):10553–60. PubMed Europe PMC Scholia
  8. Wang S, Yang Q, Fung K-M, Lin H-K. AKR1C2 and AKR1C3 mediated prostaglandin D2 metabolism augments the PI3K/Akt proliferative signaling pathway in human prostate cancer cells. Mol Cell Endocrinol. 2008 Jul 16;289(1–2):60–6. PubMed Europe PMC Scholia
  9. Bresson E, Boucher-Kovalik S, Chapdelaine P, Madore E, Harvey N, Laberge PY, et al. The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium. J Clin Endocrinol Metab. 2011 Jan;96(1):210–9. PubMed Europe PMC Scholia
  10. Seo K-S, Naidansuren P, Kim S-H, Yun S-J, Park J-J, Sim B-W, et al. Expression of aldo-keto reductase family 1 member C1 (AKR1C1) gene in porcine ovary and uterine endometrium during the estrous cycle and pregnancy. Reprod Biol Endocrinol. 2011 Oct 20;9:139. PubMed Europe PMC Scholia
  11. Bogacka I, Bogacki M, Gaglewska M, Kurzynska A, Wasielak M. In vitro effect of peroxisome proliferator activated receptor (PPAR) ligands on prostaglandin E2 synthesis and secretion by porcine endometrium during the estrous cycle and early pregnancy. J Physiol Pharmacol. 2013 Feb;64(1):47–54. PubMed Europe PMC Scholia