BioPAX pathway converted from "Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)" in the Reactome database. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Arachidonic acid is epoxidated to 5,6-EET by CYP(4) Arachidonic acid is epoxidated to 5,6-EET by CYP(4) This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 70106 1 cytosol GO 0005829 hydron [ChEBI:15378] hydron Reactome http://www.reactome.org ChEBI 15378 Reactome DB_ID: 29368 1 dioxygen [ChEBI:15379] dioxygen ChEBI 15379 Reactome DB_ID: 29364 1 NADPH(4-) [ChEBI:57783] NADPH(4-) NADPH 2'-O-phosphonatoadenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NADPH tetraanion ChEBI 57783 Reactome DB_ID: 29768 1 arachidonate [ChEBI:32395] arachidonate (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate (20:4n6) (5Z,8Z,11Z,14Z)-eicosatetraenoate ChEBI 32395 Reactome DB_ID: 29356 1 water [ChEBI:15377] water ChEBI 15377 Reactome DB_ID: 2142739 1 5,6-EET [ChEBI:34450] 5,6-EET ChEBI 34450 Reactome DB_ID: 29366 1 NADP(3-) [ChEBI:58349] NADP(3-) NADP(+) 2'-O-phosphonatoadenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NADP trianion ChEBI 58349 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10522633 endoplasmic reticulum membrane GO 0005789 CYP(1) [endoplasmic reticulum membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity cyp1a1 [endoplasmic reticulum membrane] cyp1b1 [endoplasmic reticulum membrane] Xenopus tropicalis NCBI Taxonomy 8364 UniProt A0A803K427 UniProt A0A6I8SJ30 GO 0004497 GO molecular function Reactome Database ID Release 82 10522634 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10522634 Reactome Database ID Release 82 10522643 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10522643 Reactome R-XTR-2161890 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-XTR-2161890.1 Several cytochrome P450s (CYPs) convert arachidonic acid to 5,6-epoxyeicosatrienoic acid (5,6-EET). The CYPs and their references are as follows: CYP1A1, CYP1A2, CYP1B1 (Choudhary et al. 2004); CYP2J2 (Wu et al. 1996). 8631948 Pubmed 1996 Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart Wu, S Moomaw, CR Tomer, KB Falck, JR Zeldin, DC J Biol Chem 271:3460-8 15258110 Pubmed 2004 Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1 Choudhary, D Jansson, I Stoilov, I Sarfarazi, M Schenkman, JB Drug Metab Dispos 32:840-7 inferred by electronic annotation IEA GO IEA Arachidonic acid is epoxidated to 8,9/11,12/14,15-EET by CYP(5) Arachidonic acid is epoxidated to 8,9/11,12/14,15-EET by CYP(5) This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 70106 1 Reactome DB_ID: 29368 1 Reactome DB_ID: 29364 1 Reactome DB_ID: 29768 1 Converted from EntitySet in Reactome Reactome DB_ID: 2161753 1 8,9/11,12/14,15-EET [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity 11,12-EET [cytosol] 14,15-EET [cytosol] 8,9-EET [cytosol] ChEBI 34130 ChEBI 34157 ChEBI 34490 Reactome DB_ID: 29356 1 Reactome DB_ID: 29366 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10522645 CYP(5) [endoplasmic reticulum membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity panx3 [endoplasmic reticulum membrane] cyp1a1 [endoplasmic reticulum membrane] LOC100497808 [endoplasmic reticulum membrane] cyp2a6.1 [endoplasmic reticulum membrane] cyp2a6.3 [endoplasmic reticulum membrane] cyp2a6.2 [endoplasmic reticulum membrane] cyp1b1 [endoplasmic reticulum membrane] UniProt F7D9M9 UniProt A0A6I8Q180 UniProt L7N334 UniProt A0A6I8SMY9 UniProt A8E5W6 Reactome Database ID Release 82 10522646 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10522646 Reactome Database ID Release 82 10522648 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10522648 Reactome R-XTR-2161899 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-XTR-2161899.1 Several cytochrome P450s (CYPs) convert arachidonic acid to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (8,9-, 11,12-, 14,15-EETs). The CYPs and their references are as follows: CYP1A1, CYP1A2, CYP1B1 (Choudhary et al. 2004); CYP2C8, CYP2C9 (Rifkind et al. 1995); CYP2C19 (Bylund et al. 1998, Rifkind et al. 1995); CYP2J2 (Wu et al. 1996). 9866708 Pubmed 1998 Analysis of cytochrome P450 metabolites of arachidonic and linoleic acids by liquid chromatography-mass spectrometry with ion trap MS Bylund, J Ericsson, J Oliw, EH Anal Biochem 265:55-68 7625847 Pubmed 1995 Arachidonic acid metabolism by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2: regioselective oxygenation and evidence for a role for CYP2C enzymes in arachidonic acid epoxygenation in human liver microsomes Rifkind, AB Lee, C Chang, TK Waxman, DJ Arch Biochem Biophys 320:380-9 inferred by electronic annotation IEA GO IEA 3.3.2.10 EET(1) is hydrolysed to DHET(1) by EPHX2 EET(1) is hydrolysed to DHET(1) by EPHX2 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 2161818 1 EET(1) [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity 11,12-EET [cytosol] 14,15-EET [cytosol] 5,6-EET [cytosol] 8,9-EET [cytosol] Reactome DB_ID: 29356 1 Converted from EntitySet in Reactome Reactome DB_ID: 2161883 1 DHET(1) [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity 5,6-DHET [cytosol] (5Z,8Z,11Z)-14,15-dihydroxyicosatrienoic acid [cytosol] (5Z,11Z,14Z)-8,9-dihydroxyicosatrienoic acid [cytosol] (5Z,8Z,14Z)-11,12-dihydroxyicosatrienoic acid [cytosol] ChEBI 63974 ChEBI 63966 ChEBI 63970 ChEBI 63969 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10522696 EPHX2 dimer [cytosol] EPHX2 dimer Reactome DB_ID: 10522694 2 UniProt:A0A6I8RK06 ephx2 UniProt A0A6I8RK06 Chain Coordinates 1 EQUAL 555 EQUAL Reactome DB_ID: 29926 2 magnesium(2+) [ChEBI:18420] magnesium(2+) ChEBI 18420 Reactome Database ID Release 82 10522696 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10522696 Reactome R-XTR-2142777 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-XTR-2142777.1 GO 0004301 GO molecular function Reactome Database ID Release 82 10522697 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10522697 Reactome Database ID Release 82 10522699 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10522699 Reactome R-XTR-2161961 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-XTR-2161961.1 Epoxide hydrolase 2 (EPHX2) hydrolyses 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids ("EET(1)") to their corresponding dihydroxyeicosatrienoic acids ("DHET(1)") (Werner et al. 2002; Gomez et al. 2004). The majority of the EET biological activities are diminished by this hydrolysis. 12468260 Pubmed 2002 Characterization and identification of cytochrome P450 metabolites of arachidonic acid released by human peritoneal macrophages obtained from the pouch of Douglas Werner, K Schaefer, WR Schweer, H Deppert, WR Karck, U Zahradnik, HP Prostaglandins Leukot Essent Fatty Acids 67:397-404 15096040 Pubmed 2004 Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis Gomez, GA Morisseau, C Hammock, BD Christianson, DW Biochemistry 43:4716-23 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 82 10568514 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10568514 Reactome R-XTR-2142670 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-XTR-2142670.1 GO 0019373 GO biological process The epoxidation of arachidonic acid by cytochrome P450s (CYPs) results in the formation of unique bioactive lipid mediators termed epoxyeicosatrienoic acids (EETs). Each double bond has been shown to be susceptible to oxidation, resulting in 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. The majority of the EET biological activities are diminished by the hydrolysis to the corresponding dihydroxyeicosatrienoic acids (DHET) (Capdevila et al. 2000, Buczynski et al. 2009, Vance & Vance 2008). 10681399 Pubmed 2000 Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase Capdevila, JH Falck, JR Harris, RC J Lipid Res 41:163-81 19244215 Pubmed 2009 Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology Buczynski, MW Dumlao, DS Dennis, EA J Lipid Res 50:1015-38 978-0-444-53219-0 ISBN 2008 The eicosanoids: cyclooxygenase, lipoxygenase, and epoxygenase pathways Smith, William L Murphy, RC Biochemistry of Lipids, Lipoproteins and Membranes, 5th Edition (Book): 331-362 inferred by electronic annotation IEA GO IEA