BioPAX pathway converted from "alpha-linolenic (omega3) and linoleic (omega6) acid metabolism" in the Reactome database.alpha-linolenic (omega3) and linoleic (omega6) acid metabolismalpha-linolenic (omega3) and linoleic (omega6) acid metabolismThis 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>alpha-linolenic acid (ALA) metabolismalpha-linolenic acid (ALA) metabolismThis 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>6.2.1.3Activation of alpha-linolenic acid to alpha-linolenoyl-CoAActivation of alpha-linolenic acid to alpha-linolenoyl-CoAThis 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: 2115791endoplasmic reticulum membraneGO0005789ATP(4-) [ChEBI:30616]ATP(4-)Adenosine 5'-triphosphateatpATPReactomehttp://www.reactome.orgChEBI30616Reactome DB_ID: 20460561endoplasmic reticulum lumenGO0005788alpha-linolenic acid [ChEBI:27432]alpha-linolenic acidChEBI27432Reactome DB_ID: 1627431coenzyme A [ChEBI:15346]coenzyme AChEBI15346Reactome DB_ID: 20460621alpha-linolenoyl-CoA [ChEBI:51985]alpha-linolenoyl-CoAcis,cis-9,12-octadecadienoyl-CoAcis-Delta(9,12)-octadecadienoyl-CoAcis-Delta(9,12)-octadecadienoyl-coenzyme Acis,cis-9,12-octadecadienoyl-coenzyme Aalpha-linolenoyl-coenzyme Acis,cis-linoleoyl-CoAcis,cis-linoleoyl-coenzyme AChEBI51985Reactome DB_ID: 20460641adenosine 5'-monophosphate [ChEBI:16027]adenosine 5'-monophosphateChEBI16027Reactome DB_ID: 20460491diphosphoric acid [ChEBI:29888]diphosphoric acidChEBI29888PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9880010ACSL1 [endoplasmic reticulum membrane]ACSL1Reactome DB_ID: 2173141magnesium(2+) [ChEBI:18420]magnesium(2+)ChEBI18420Reactome DB_ID: 98412631UniProt:P18163Acsl1Rattus norvegicusNCBI Taxonomy10116UniProtP18163Chain Coordinates1EQUAL698EQUALReactome Database ID Release 759880010Database 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=9880010ReactomeR-RNO-20460751Reactome 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-RNO-2046075.1GO0004467GO molecular functionReactome Database ID Release 759880011Database 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=9880011Reactome Database ID Release 759880013Database 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=9880013ReactomeR-RNO-20460851Reactome 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-RNO-2046085.1In the first step the precursor apha-linolenic (9,12,15-18:3(n-3)) acid is activated to a high energy form known as alpha-linolenoyl-CoA (9Z,12Z,15Z-octadecatrienoyl-CoA) by the iron enzyme long-chain-fatty-acid-CoA-ligase (acyl-CoA synthetase 1, ACSL1) and coenzyme A.7061494Pubmed1982Discovery of an arachidonoyl coenzyme A synthetase in human plateletsWilson, DBPrescott, SMMajerus, PWJ Biol Chem 257:3510-5978-0-12-417762-8ISBN2003Docosahexaenoic acidBiosketch, KohlmeierNutrient Metabolism (Book): 164-175inferred by electronic annotationIEAGOIEA1.14.19.3Desaturation of alpha-linoleoyl-CoA to Stearidonoyl-CoADesaturation of alpha-linoleoyl-CoA to Stearidonoyl-CoAThis 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: 20460621Reactome DB_ID: 1946972NADH(2-) [ChEBI:57945]NADH(2-)NADH dianionadenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] diphosphate}NADHChEBI57945Reactome DB_ID: 1135341dioxygen [ChEBI:15379]dioxygenChEBI15379Reactome DB_ID: 20460521(6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA [ChEBI:63545](6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoAChEBI63545Reactome DB_ID: 1135192water [ChEBI:15377]waterChEBI15377Reactome DB_ID: 1946532NAD(1-) [ChEBI:57540]NAD(1-)NAD(+)adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate}NAD anionChEBI57540PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 2046068UniProt:Q9Z122 Fads2Fads2Fads2Fadsd6FUNCTION Involved in the biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors, acting as a fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 6 of the fatty acyl chain. Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively (PubMed:10049752, PubMed:22216341, PubMed:11988075, PubMed:14563830, PubMed:24070791). Subsequently, in the biosynthetic pathway of HUFA n-3 series, it desaturates tetracosapentaenoate (24:5n-3) to tetracosahexaenoate (24:6n-3), which is then converted to docosahexaenoate (DHA)(22:6n-3), an important lipid for nervous system function (PubMed:11988075). It can also desaturate (11E)-octadecenoate (trans-vaccenoate) at carbon 6 generating (6Z,11E)-octadecadienoate (PubMed:24070791). In addition to Delta-6 activity, this enzyme exhibits Delta-8 activity with slight biases toward n-3 fatty acyl-CoA substrates (By similarity).PATHWAY Lipid metabolism; polyunsaturated fatty acid biosynthesis.TISSUE SPECIFICITY Expressed in the liver and brain (at protein level) (PubMed:11988075). Highest activity is found in the liver and adrenals followed by the testes and other organs, absent in adipose tissue (PubMed:5094766).INDUCTION Inhibited by a shortage of insulin and an increase of glucagon.DOMAIN The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes HXXXH, HXXHH, and QXXHH (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases.SIMILARITY Belongs to the fatty acid desaturase type 1 family.UniProtQ9Z1221EQUAL444EQUALGO0016213GO molecular functionReactome Database ID Release 759880006Database 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=9880006Reactome Database ID Release 759880008Database 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=9880008ReactomeR-RNO-20460841Reactome 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-RNO-2046084.1Alpha-linoloyl-CoA is converted to Stearidonoyl-CoA (SDA, 6,9,12,15-18:3(n-3)) by delta-6-destaurase (fatty acid desaturase-2, FADS2). FADS2 uses the cytochrome b5 system to add a double bond at position 6. This is the rate limiting step in alpha-linolenic acid (ALA) metabolism (Horrobin 1993).11988075Pubmed2002The same rat Delta6-desaturase not only acts on 18- but also on 24-carbon fatty acids in very-long-chain polyunsaturated fatty acid biosynthesisd'Andréa, SGuillou, HJan, SCatheline, DThibault, JNBouriel, MRioux, VLegrand, PBiochem J 364:49-5512562861Pubmed2003Regulation of human delta-6 desaturase gene transcription: identification of a functional direct repeat-1 elementTang, CCho, HPNakamura, MTClarke, SDJ Lipid Res 44:686-951346092Pubmed1992Comparison of the conversion rates of alpha-linolenic acid (18:3(n - 3)) and stearidonic acid (18:4(n - 3)) to longer polyunsaturated fatty acids in ratsYamazaki, KFujikawa, MHamazaki, TYano, SShono, TBiochim Biophys Acta 1123:18-2612713571Pubmed2003Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activityGe, LGordon, JSHsuan, CStenn, KProuty, SMJ Invest Dermatol 120:707-148386433Pubmed1993Fatty acid metabolism in health and disease: the role of delta-6-desaturaseHorrobin, DFAm J Clin Nutr 57:732S-736S; discussion 736S-737S19056654Pubmed2009Dietary stearidonic acid is a long chain (n-3) polyunsaturated fatty acid with potential health benefitsWhelan, JJ Nutr 139:5-10inferred by electronic annotationIEAGOIEAElongation of stearidonoyl-CoA to eicosatetraenoyl-CoAElongation of stearidonoyl-CoA to eicosatetraenoyl-CoAThis 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: 20460521Reactome DB_ID: 1136012NADPH [ChEBI:16474]NADPHTPNHChEBI16474Reactome DB_ID: 20460661malonyl-CoA [ChEBI:15531]malonyl-CoAChEBI15531Reactome DB_ID: 20460511(8Z,11Z,14Z,17Z)-icosatetraenoyl-CoA [ChEBI:63542](8Z,11Z,14Z,17Z)-icosatetraenoyl-CoAChEBI63542Reactome DB_ID: 1135191Reactome DB_ID: 1135642NADP(+) [ChEBI:18009]NADP(+)ChEBI18009Reactome DB_ID: 1597511carbon dioxide [ChEBI:16526]carbon dioxideChEBI16526Reactome DB_ID: 1627431PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 9859458ELOVL1,2,3,5 [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityElovl2 [endoplasmic reticulum membrane]Elovl3 [endoplasmic reticulum membrane]Elovl5 [endoplasmic reticulum membrane]Elovl1 [endoplasmic reticulum membrane]UniProtD4A612UniProtD3ZPX9UniProtQ920L7UniProtQ5U2Z8GO0009922GO molecular functionReactome Database ID Release 759859459Database 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=9859459Reactome Database ID Release 759880018Database 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=9880018ReactomeR-RNO-20460881Reactome 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-RNO-2046088.1SDA-CoA (6,9,12,15-18:4(n-3)) is rapidly elongated by two carbon atoms to 8,11,14,17-eicosatetraenoyl-CoA (8,11,14,17-20:4(n-3), ETA-CoA). The NADPH-consuming enzyme long-chain fatty acyl elongase (ELOVL5) mediates this reaction which and adds malonyl-CoA to the SDA-CoA and releases carbon dioxide and free CoA (Leonard et al. 2004). 14636670Pubmed2004Elongation of long-chain fatty acidsLeonard, AEPereira, SLSprecher, HHuang, YSProg Lipid Res 43:36-5410899997Pubmed2000Identification and characterization of an enzyme involved in the elongation of n-6 and n-3 polyunsaturated fatty acidsParker-Barnes, JMDas, TBobik, ELeonard, AEThurmond, JMChaung, LTHuang, YSMukerji, PProc Natl Acad Sci U S A 97:8284-912716664Pubmed2003Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acidsJames, MJUrsin, VMCleland, LGAm J Clin Nutr 77:1140-5inferred by electronic annotationIEAGOIEADesaturation of eicosatetraenoyl-CoA to eicosapentaenoyl-CoADesaturation of eicosatetraenoyl-CoA to eicosapentaenoyl-CoAThis 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: 1946972Reactome DB_ID: 20460511Reactome DB_ID: 1135341Reactome DB_ID: 20460591(5Z,8Z,11Z,14Z,17Z)-icosapentaenoyl-CoA [ChEBI:63539](5Z,8Z,11Z,14Z,17Z)-icosapentaenoyl-CoAChEBI63539Reactome DB_ID: 1135192Reactome DB_ID: 1946532PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9880022UniProt:Q920R3Fads1UniProtQ920R31EQUAL501EQUALGO0045485GO molecular functionReactome Database ID Release 759880023Database 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=9880023Reactome Database ID Release 759880025Database 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=9880025ReactomeR-RNO-20460891Reactome 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-RNO-2046089.1Eicosatetraenoyl-CoA (ETA-CoA) is desaturated by an additional carbon-carbon bond to form 5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl-CoA (EPA-CoA, 5,8,11,14,17-20:5(n-3)). Delta-5-desaturase is required for this conversion. EPA-CoA has health benefits due to its anti-inflammatory actions. It is a precursor for the anti-inflammatory series-3 prostaglandins (PG), the series-5 leukotrienes (LT) and the series-3 thromboxanes (TA), which are anti-atherogenic and anti-thrombogenic (Ross et al. 2009).10601301Pubmed1999Cloning, expression, and fatty acid regulation of the human delta-5 desaturaseCho, HPNakamura, MClarke, SDJ Biol Chem 274:37335-919422375Pubmed2009Long-chain n-3 polyunsaturated fatty acids: new insights into mechanisms relating to inflammation and coronary heart diseasede Roos, BMavrommatis, YBrouwer, IABr J Pharmacol 158:413-288096621Pubmed1993Comparison of the metabolism of alpha-linolenic acid and its delta 6 desaturation product, stearidonic acid, in cultured NIH-3T3 cellsCantrill, RCHuang, YSElls, GWHorrobin, DFLipids 28:163-6inferred by electronic annotationIEAGOIEAElongation of eicosapentaenoyl-CoA to docosapentaenoyl-CoAElongation of eicosapentaenoyl-CoA to docosapentaenoyl-CoAThis 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: 20460591Reactome DB_ID: 1136012Reactome DB_ID: 20460661Reactome DB_ID: 20460571(7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA [ChEBI:63541](7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoAChEBI63541Reactome DB_ID: 1135191Reactome DB_ID: 1135642Reactome DB_ID: 1597511Reactome DB_ID: 1627431PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 9880001ELOVL5/ELOVL2 [endoplasmic reticulum membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityElovl2 [endoplasmic reticulum membrane]Elovl5 [endoplasmic reticulum membrane]Reactome Database ID Release 759880002Database 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=9880002Reactome Database ID Release 759880044Database 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=9880044ReactomeR-RNO-20461001Reactome 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-RNO-2046100.1Eicosapentaenoyl-CoA (EPA-CoA) is transformed to docosapentaenoyl-CoA (DPA-CoA/clupanodonic acid; 7,10,13,16,19-22:5(n-3)) by addition of two carbon atoms from malanoyl-CoA. This reaction is catalyzed by the enzymes ELOVL5/2 (Leonard et al. 2004). DPA is quite high in seal oil and may act as an anti-atherogenic factor. DPA has 10-fold greater endothelial cell migration ability than EPA, which is important in wound-healing processes. DPA may act as a precursor for production of the DPA-related D-series of resolvins or neuroprotectins (Kaur et al. 2011).12323090Pubmed2002Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young womenBurdge, Graham CWootton, SABr J Nutr 88:411-208832760Pubmed1996Docosapentaenoic acid (22:5, n-3), an elongation metabolite of eicosapentaenoic acid (20:5, n-3), is a potent stimulator of endothelial cell migration on pretreatment in vitroKanayasu-Toyoda, TMorita, IMurota, SProstaglandins Leukot Essent Fatty Acids 54:319-2520655949Pubmed2011Docosapentaenoic acid (22:5n-3): a review of its biological effectsKaur, GCameron-Smith, DGarg, MSinclair, AJProg Lipid Res 50:28-3412323085Pubmed2002Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*Burdge, Graham CJones, AEWootton, SABr J Nutr 88:355-63inferred by electronic annotationIEAGOIEAElongation of docosapentaenoyl-CoA to tetracosapentaenoyl-CoAElongation of docosapentaenoyl-CoA to tetracosapentaenoyl-CoAThis 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: 20460571Reactome DB_ID: 1136012Reactome DB_ID: 20460661Reactome DB_ID: 20460651(9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoA [ChEBI:63543](9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoAChEBI63543Reactome DB_ID: 1135191Reactome DB_ID: 1135642Reactome DB_ID: 1597511Reactome DB_ID: 1627431PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9859448UniProt:D4A612Elovl21EQUAL296EQUALReactome Database ID Release 759880026Database 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=9880026Reactome Database ID Release 759880028Database 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=9880028ReactomeR-RNO-20460901Reactome 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-RNO-2046090.1Docosapentaenoyl-CoA is elongated to tetracosapentaenoyl-CoA (9,12,15,18,21-24:5(n-3)) by the enzyme ELOVL2.1834642Pubmed1991The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturaseVoss, AReinhart, MSankarappa, SSprecher, HJ Biol Chem 266:19995-20000inferred by electronic annotationIEAGOIEA7.6.2.4Translocation of tetracosahexaenoyl-CoA to peroxisomesTranslocation of tetracosahexaenoyl-CoA to peroxisomesThis 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: 2115791Reactome DB_ID: 20460541(6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA [ChEBI:63540](6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoAChEBI63540Reactome DB_ID: 42663911-phosphatidyl-1D-myo-inositol [ChEBI:16749]1-phosphatidyl-1D-myo-inositolChEBI16749Reactome DB_ID: 2116061ADP(3-) [ChEBI:456216]ADP(3-)ADP trianion5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADPChEBI456216Reactome DB_ID: 20460471peroxisomal matrixGO0005782PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9851387peroxisomal membraneGO0005778UniProt:D3ZHR2Abcd1UniProtD3ZHR21EQUAL745EQUALGO0005324GO molecular functionReactome Database ID Release 759880014Database 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=9880014Reactome Database ID Release 759880016Database 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=9880016ReactomeR-RNO-20460871Reactome 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-RNO-2046087.1The 24-carbon tetracosahexaenoyl-CoA (6,9,12,15,18,21-24:6(n-3) is transported to peroxisomes to undergo a putative single cycle of peroxisomal beta-oxidation, producing Docosahexaenoic Acid (DHA) (Sprecher 2002, Luthria et al. 1996).8663162Pubmed1996Regulation of the biosynthesis of 4,7,10,13,16,19-docosahexaenoic acidLuthria, DLMohammed, BSSprecher, HJ Biol Chem 271:16020-58656081Pubmed1995Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acidMoore, SAHurt, EYoder, ESprecher, HSpector, AAJ Lipid Res 36:2433-4311500517Pubmed2001Peroxisomal straight-chain Acyl-CoA oxidase and D-bifunctional protein are essential for the retroconversion step in docosahexaenoic acid synthesisSu, HMMoser, ABMoser, HWWatkins, PAJ Biol Chem 276:38115-2012897190Pubmed2003Studies on the metabolic fate of n-3 polyunsaturated fatty acidsFerdinandusse, SachaDenis, SimoneDacremont, GeorgesWanders, Ronald J AJ Lipid Res 44:1992-712324224Pubmed2002The roles of anabolic and catabolic reactions in the synthesis and recycling of polyunsaturated fatty acidsSprecher, HProstaglandins Leukot Essent Fatty Acids 67:79-83inferred by electronic annotationIEAGOIEA1.3.3.6Oxidation of tetracosapentaenoyl-CoA to delta2-tetracosaheptaenoyl-CoAOxidation of tetracosapentaenoyl-CoA to delta2-tetracosaheptaenoyl-CoAThis 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: 1135351Reactome DB_ID: 20460471Reactome DB_ID: 20667671(2E,6Z,9Z,12Z,15Z,18Z,21Z)-tetracosaheptaenoyl-CoA [ChEBI:65139](2E,6Z,9Z,12Z,15Z,18Z,21Z)-tetracosaheptaenoyl-CoAChEBI65139Reactome DB_ID: 1135751hydrogen peroxide [ChEBI:16240]hydrogen peroxideChEBI16240PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9851966ACOX1 dimer [peroxisomal matrix]ACOX1 dimerReactome DB_ID: 98519642ACOX1:FAD complex [peroxisomal matrix]ACOX1:FAD complexReactome DB_ID: 98519621UniProt:P07872 Acox1Acox1Acox1AcoxFUNCTION Catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs (PubMed:7462191, PubMed:1400324, PubMed:7503725). Isoform 1 shows highest activity against medium-chain fatty acyl-CoAs and activity decreases with increasing chain length (PubMed:7503725). Isoform 2 is active against a much broader range of substrates and shows activity towards very long-chain acyl-CoAs (PubMed:7503725). Isoform 1 shows optimum activity with a chain length of 10 carbons while isoform 2 exhibits optimum activity with 14 carbons (PubMed:7503725).PATHWAY Lipid metabolism; peroxisomal fatty acid beta-oxidation.SUBUNIT Homodimer. The enzyme contains three components A, B and C, the latter two being produced from the first by a proteolytic cleavage. Interacts with LONP2 (By similarity).SIMILARITY Belongs to the acyl-CoA oxidase family.UniProtP078721EQUAL660EQUALReactome DB_ID: 1413351FAD [ChEBI:16238]FADFlavin adenine dinucleotideChEBI16238Reactome Database ID Release 759851964Database 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=9851964ReactomeR-RNO-3902371Reactome 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-RNO-390237.1Reactome Database ID Release 759851966Database 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=9851966ReactomeR-RNO-3902321Reactome 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-RNO-390232.1GO0003997GO molecular functionReactome Database ID Release 759851967Database 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=9851967Reactome Database ID Release 759880283Database 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=9880283ReactomeR-RNO-20667871Reactome 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-RNO-2066787.1Retroconversion of C24:6(n-3) to docosahexaenoic acid (22:6(n-3) involves the initial oxidation of tetracosahexaenoyl-CoA to an intermediate 1-(2E,6Z,9Z,12Z,15Z,18Z,21Z-tetracosaheptaenoyl)-CoA (delta2-THA-CoA). This step is catalysed by the peroxisomal enzyme Straight-chain acyl-CoA oxidase (SCOX) (Ferdinandusse et al. 2001).11734571Pubmed2001Identification of the peroxisomal beta-oxidation enzymes involved in the biosynthesis of docosahexaenoic acidFerdinandusse, SachaDenis, SimoneMooijer, PAZhang, ZReddy, Janardan KSpector, AAWanders, Ronald J AJ Lipid Res 42:1987-95inferred by electronic annotationIEAGOIEA4.2.1.74Hydration of delta2-tetracosaheptaenoyl-CoA to 3-hydroxy tetracosahexaenoyl-CoAHydration of delta2-tetracosaheptaenoyl-CoA to 3-hydroxy tetracosahexaenoyl-CoAThis 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: 20667671Reactome DB_ID: 1413431Reactome DB_ID: 20667661(6Z,9Z,12Z,15Z,18Z,21Z)-3-hydroxytetracosahexaenoyl-CoA [ChEBI:65130](6Z,9Z,12Z,15Z,18Z,21Z)-3-hydroxytetracosahexaenoyl-CoAChEBI65130PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9838240HSD17B4 dimer [peroxisomal matrix]HSD17B4 dimerReactome DB_ID: 98382382UniProt:P97852Hsd17b4UniProtP978521EQUAL736EQUALReactome Database ID Release 759838240Database 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=9838240ReactomeR-RNO-3899991Reactome 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-RNO-389999.1GO0016508GO molecular functionReactome Database ID Release 759851951Database 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=9851951Reactome Database ID Release 759880277Database 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=9880277ReactomeR-RNO-20667781Reactome 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-RNO-2066778.1Delta2-THA-CoA is hydrated to 3-hydroxyacyl-CoA intermediate 1-(3-hydroxy-6Z,9Z,12Z,15Z,18Z,21Z-tetracosahexaenoyl)-CoA by HSD17B4/DBP (d-bifunctional protein) dimer.9089413Pubmed1997Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional proteinJiang, LLMiyazawa, SSouri, MHashimoto, TakashiJ Biochem 121:364-9inferred by electronic annotationIEAGOIEA4.2.1.74Dehydrogenation of 3-hydroxy tetracosahexaenoyl-CoADehydrogenation of 3-hydroxy tetracosahexaenoyl-CoAThis 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: 20667661Reactome DB_ID: 20667621(6Z,9Z,12Z,15Z,18Z,21Z)-3-oxotetracosahexaenoyl-CoA [ChEBI:65131](6Z,9Z,12Z,15Z,18Z,21Z)-3-oxotetracosahexaenoyl-CoAChEBI65131PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9838240Reactome Database ID Release 759880281Database 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=9880281ReactomeR-RNO-20667801Reactome 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-RNO-2066780.13-hydroxy tetracosahexaenoyl-CoA undergoes dehydrogenation to form 1-(3-oxo-6Z,9Z,12Z,15Z,18Z,21Z-tetracosahexaenoyl)-CoA, catalysed by DBP. DBP is a bifunctional enzyme, involved in the hydration of a variety of trans-2,3-dehydroacyl-CoA's but also mediating dehydrogenation of a variety of 3-hydroxyacyl-CoA's (Jiang et al. 1997).inferred by electronic annotationIEAGOIEA3.1.2.1Conversion of DHA-CoA to docosahexaenoic acid (DHA)Conversion of DHA-CoA to docosahexaenoic acid (DHA)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: 1413431Reactome DB_ID: 20667651(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA [ChEBI:65132](4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoAChEBI65132Reactome DB_ID: 1935141Reactome DB_ID: 20667631all-cis-docosa-4,7,10,13,16,19-hexaenoic acid [ChEBI:28125]all-cis-docosa-4,7,10,13,16,19-hexaenoic acidChEBI28125PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9838417UniProt:Q8VHK0Acot8UniProtQ8VHK01EQUAL319EQUALGO0003986GO molecular functionReactome Database ID Release 759851986Database 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=9851986Reactome Database ID Release 759880279Database 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=9880279ReactomeR-RNO-20667791Reactome 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-RNO-2066779.1DHA-CoA preferentially moves back to the ER, perhaps as a free fatty acid. This conversion is usually catalysed by acyl-CoA thioesterases (ACOTs). No specific acyl-CoA thioesterase enzyme has been identified for the peroxisomal metabolism of DHA-CoA, but the peroxisomal ACOT8 has a wide substrate specificity and is likely to be responsible (Ferdinandusse et al. 2003, Hunt & Alexson. 2008).18538142Pubmed2008Novel functions of acyl-CoA thioesterases and acyltransferases as auxiliary enzymes in peroxisomal lipid metabolismHunt, MCAlexson, SEProg Lipid Res 47:405-21inferred by electronic annotationIEAGOIEAReactome Database ID Release 759929870Database 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=9929870ReactomeR-RNO-20461061Reactome 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-RNO-2046106.1GO0036109GO biological processAlpha-linolenic acid (ALA, 18:3(n-3)) is an omega-3 fatty acid, supplied through diet as it cannot be synthesized by humans. ALA has an important role in human health. It is converted to long chain more unsaturated n-3 fatty acids by a series of alternating desaturation and elongation reactions. Omega-3 products of ALA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce inflammation and may help lower risk of chronic diseases, such as heart disease and arthritis. All the desaturation and elongation steps occur in the endoplasmic reticulum (ER) except for the final step which requires translocation to peroxisomes for partial beta-oxidation.<br><br>The alpha-linolenic acid pathway involves the following steps: 18:3(n-3)--> 18:4(n-3)-->20:4(n-3)-->20:5(n-3)-->22:5(n-3)-->24:5(n-3)-->24:6(n-3)-->22:6(n-3). Two desaturation enzymes are involved in this process: delta-6 desaturase that converts 18:3(n-3) to 18:4(n-3) and 24:5(n-3) to 24:6(n-3) respectively, delta-5 desaturase 20:4(n-3) to 20:5(n-3). (Sprecher 2002).16828546Pubmed2006Metabolism of alpha-linolenic acid in humansBurdge, Graham CProstaglandins Leukot Essent Fatty Acids 75:161-88443237Pubmed1993Desaturation and chain elongation of n - 3 and n - 6 polyunsaturated fatty acids in the human CaCo-2 cell lineChen, QNilsson, ABiochim Biophys Acta 1166:193-201inferred by electronic annotationIEAGOIEALinoleic acid (LA) metabolismLinoleic acid (LA) metabolismThis 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>6.2.1.3Activation of linoleic acid to linoleoyl-CoAActivation of linoleic acid to linoleoyl-CoAThis 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: 2115791Reactome DB_ID: 20460441linoleic acid [ChEBI:17351]linoleic acidChEBI17351Reactome DB_ID: 1627431Reactome DB_ID: 20460641Reactome DB_ID: 20460631linoleoyl-CoA [ChEBI:15530]linoleoyl-CoAChEBI15530Reactome DB_ID: 20460491PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9880010Reactome Database ID Release 759880042Database 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=9880042ReactomeR-RNO-20460981Reactome 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-RNO-2046098.1The dietary essential fatty acid (EFA) linoleic acid (LA) is activated to a high energy form known as linoleoyl-CoA by the action of long-chain acyl-CoA synthetases (ACSLs). Thioesterification of long-chain fatty acids into their acyl-CoA derivatives is considered to be the first committed step in fatty acid metabolism. Formation of acyl-CoA allows an otherwise non-reactive fatty acid to participate in biosynthetic or catabolic pathways. This acyl CoA form is converted to its longer-chain polyunsaturated products by a series of desaturation and elongation reactions (Ellis et al. 2010, Watkins 2008).18024425Pubmed2008Very-long-chain acyl-CoA synthetasesWatkins, PAJ Biol Chem 283:1773-720480548Pubmed2010Acyl-coenzyme A synthetases in metabolic controlEllis, JMFrahm, JLLi, LOColeman, RACurr Opin Lipidol 21:212-7inferred by electronic annotationIEAGOIEA1.14.19.3Desaturation of Linoleoyl-CoA to gamma-linolenoyl-CoADesaturation of Linoleoyl-CoA to gamma-linolenoyl-CoAThis 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: 1946972Reactome DB_ID: 20460631Reactome DB_ID: 1135341Reactome DB_ID: 20460421gamma-linolenoyl-CoA [ChEBI:15508]gamma-linolenoyl-CoAChEBI15508Reactome DB_ID: 1135192Reactome DB_ID: 1946532PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 20460681EQUAL444EQUALReactome Database ID Release 759880038Database 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=9880038ReactomeR-RNO-20460961Reactome 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-RNO-2046096.1The first major step in the metabolism of linoleic acid (LA) is desaturation of delta 9,12-octadecadienoyl CoA/linoleoyl CoA (LA-CoA) to delta 6,9,12-octodecatrienoyl CoA/gamma-lenoleoyl CoA (GLA-CoA). This step is catalyzed by delta-6-destaurase (fatty acid desaturase-2, FADS2) which introduces a cis-double bond between carbons 6 and 7. This is the rate limiting step in LA metabolism (Horrobin 1993).inferred by electronic annotationIEAGOIEAElongation of gamma-lenolenoyl-CoA to dihomo-gamma-lenolenoyl-CoAElongation of gamma-lenolenoyl-CoA to dihomo-gamma-lenolenoyl-CoAThis 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: 20460421Reactome DB_ID: 1136012Reactome DB_ID: 20460661Reactome DB_ID: 1135191Reactome DB_ID: 1135642Reactome DB_ID: 1597511Reactome DB_ID: 20460451all-cis-icosa-8,11,14-trienoyl-CoA [ChEBI:27979]all-cis-icosa-8,11,14-trienoyl-CoAChEBI27979Reactome DB_ID: 1627431PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 9859458Reactome Database ID Release 759880034Database 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=9880034ReactomeR-RNO-20460941Reactome 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-RNO-2046094.1Gamma-linolenoyl-CoA (6,9,12-20:3(n-6)) is rapidly elongated to dihomo-gamma-linolenoyl-CoA (DGL-CoA; 8,11,14-20:3(n-6)) by the action of C18-PUFA-specific elongase 5 (ELOVL5). Two carbon atoms are added during this reaction. DGL-CoA later undergoes desaturation to form arachidonic acid (AA, 5,8,11,14-20:4(n-6)). <br>Depending on the cell type, DGL-CoA can also be metabolized by cyclooxygenases and lipoxygenases to produce anti-inflammatory eicosanoids (prostaglandins of series 1 (PGE1) and 15-hydroxyeico- satrienoic acid (15-HETrE)). GLA and these two oxidative metabolites exert clinical effects in a variety of diseases, including suppression of chronic inflammation, vasodilation and lowering of blood pressure, inhibition of platelet aggregation and thrombosis. (Fan et al. 2001, Fan & Chapkin 1998, Kapoor & Huang. 2006)8609415Pubmed1996Metabolism of gammalinolenic acid in human neutrophilsChilton-Lopez, TSurette, MESwan, DDFonteh, ANJohnson, MMChilton, FHJ Immunol 156:2941-71-893997-17-0ISBN2001Antiatherogenic Potential of gamma Linolenic AcidFan, YYChapkin, RSRamos, KSgamma-linolenic acid (Book): 16917168669Pubmed2006Gamma linolenic acid: an antiinflammatory omega-6 fatty acidKapoor, RHuang, YSCurr Pharm Biotechnol 7:531-410970790Pubmed2000Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acidsLeonard, AEBobik, EGDorado, JKroeger, PEChuang, LTThurmond, JMParker-Barnes, JMDas, THuang, YSMukerji, PBiochem J 350:765-709732298Pubmed1998Importance of dietary gamma-linolenic acid in human health and nutritionFan, YYChapkin, RSJ Nutr 128:1411-4inferred by electronic annotationIEAGOIEADesaturation of dihomo-gamma-lenolenoyl-CoA to arachidonoyl-CoADesaturation of dihomo-gamma-lenolenoyl-CoA to arachidonoyl-CoAThis 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: 1946972Reactome DB_ID: 1135341Reactome DB_ID: 20460451Reactome DB_ID: 1135192Reactome DB_ID: 1946532Reactome DB_ID: 20460531arachidonoyl-CoA [ChEBI:15514]arachidonoyl-CoAChEBI15514PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 98800221EQUAL501EQUALReactome Database ID Release 759880030Database 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=9880030ReactomeR-RNO-20460921Reactome 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-RNO-2046092.1DGL-CoA (8,11,14-eicosatrienoyl-CoA) undergoes desaturation by delta 5-desaturase (D5-desaturase) forming arachidonoyl-CoA (AA-CoA, 5,8,11,14-Eicosatetraenoic acid). D5-desaturase has 62% sequence identity with D6-desaturase but desaturates a different carbon atom, adding a double bond at position C5 in arachidonoyl-CoA (AA-CoA). AA can be metabolized by variety of oxygenases (including cyclo-oxygenase and lipoxygenase systems) to form a family of varying products known as eicosanoids, prostaglandins, leukotrines and thromboxanes thus playing important role in inflamation response.10769175Pubmed2000cDNA cloning and characterization of human Delta5-desaturase involved in the biosynthesis of arachidonic acidLeonard, AEKelder, BBobik, EGChuang, LTParker-Barnes, JMThurmond, JMKroeger, PEKopchick, JJHuang, YSMukerji, PBiochem J 347:719-24inferred by electronic annotationIEAGOIEAElongation of arachidonyl-CoA to docosatetraenoyl-CoAElongation of arachidonyl-CoA to docosatetraenoyl-CoAarachidonoyl-CoA + malonyl-CoA => 3-oxo-(7,10,13,16)-docosatetraenoyl-CoA + CO2 + CoASH [ELOVL5]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: 1136012Reactome DB_ID: 20460661Reactome DB_ID: 20460531Reactome DB_ID: 1135191Reactome DB_ID: 1597511Reactome DB_ID: 20460601(7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA [ChEBI:63544](7Z,10Z,13Z,16Z)-docosatetraenoyl-CoAChEBI63544Reactome DB_ID: 1627431PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 9880001Reactome Database ID Release 759880004Database 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=9880004ReactomeR-RNO-20460831Reactome 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-RNO-2046083.1Arachidonyl-CoA undergoes a two-carbon chain elongation on the carboxyl end to form docosatetraenoyl-CoA (DTA-CoA/Adrenic acid/7,10,13,16-docosatetraenoic acid (7,10,13,16-22:4(n-6)). This reaction is catalyzed by the enzymes ELOVL5 or ELOVL2. Malanoyl-CoA provides the additional two carbons required for elongation. Docosatetraenoyl-CoA is further metabolized by cyclooxygenases (COX), lipoxygenases (LO) and cytochrome P450s (CYP450s) to dihomo (DH) eicosanoids (Kopf et al. 2010, Leonard et al. 2004).20038752Pubmed2010Adrenic acid metabolites as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factorsKopf, PGZhang, DXGauthier, KMNithipatikom, KYi, XYFalck, JRCampbell, WBHypertension 55:547-54inferred by electronic annotationIEAGOIEAElongation of docosatetraenoyl-CoA to tetracosatetraenoyl-CoAElongation of docosatetraenoyl-CoA to tetracosatetraenoyl-CoAThis 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: 1136012Reactome DB_ID: 20460661Reactome DB_ID: 20460601Reactome DB_ID: 20460481(9Z,12Z,15Z,18Z)-tetracosatetraenoyl-CoA [ChEBI:63548](9Z,12Z,15Z,18Z)-tetracosatetraenoyl-CoAChEBI63548Reactome DB_ID: 1135191Reactome DB_ID: 1597511Reactome DB_ID: 1627431PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 98594481EQUAL296EQUALReactome Database ID Release 759880036Database 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=9880036ReactomeR-RNO-20460951Reactome 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-RNO-2046095.1Docosatetraenoyl-CoA is elongated to tetracosatetraenoyl-CoA (TTA-CoA, 9,12,15,18-tetracosatetraenoic acid, 9,12,15,18-24:4(n-6)) by the elongase enzyme ELOVL2.5411545Pubmed1970The biosynthesis of delta-9,12,15,18-tetracosatetraenoic and of delta-6,9,12,15,18-tetracosapentaenoic acids by rat testesBridges, RBConiglio, JGJ Biol Chem 245:46-99704073Pubmed1973Fate of linoleic, arachidonic, and docosa-7,10,13,16-tetraenoic acids in rat testiclesAyala, SGaspar, GBrenner, RRPeluffo, ROKunau, WJ Lipid Res 14:296-305inferred by electronic annotationIEAGOIEA1.14.19.3Desaturation of tetracosatetraenoyl-CoA to tetracosapentaenoyl-CoADesaturation of tetracosatetraenoyl-CoA to tetracosapentaenoyl-CoAThis 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: 1946972Reactome DB_ID: 20460481Reactome DB_ID: 1135341Reactome DB_ID: 20460501(6Z,9Z,12Z,15Z,18Z)-tetracosapentaenoyl-CoA [ChEBI:63546](6Z,9Z,12Z,15Z,18Z)-tetracosapentaenoyl-CoAChEBI63546Reactome DB_ID: 1135192Reactome DB_ID: 1946532PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 20460681EQUAL444EQUALReactome Database ID Release 759880040Database 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=9880040ReactomeR-RNO-20460971Reactome 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-RNO-2046097.1Tetracosatetraenoyl-CoA is further desaturated by delta 6-desaturase (FADS2) to tetracosapentaenoyl-CoA (TPA-CoA, 6,9,12,15,18-24:5(n-6)).inferred by electronic annotationIEAGOIEA7.6.2.4Translocation of tetracosapentaenoyl-CoA to peroxisomesTranslocation of tetracosapentaenoyl-CoA to peroxisomesThis 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: 2115791Reactome DB_ID: 20460501Reactome DB_ID: 20460551Reactome DB_ID: 52283391hydrogenphosphate [ChEBI:43474]hydrogenphosphate[PO3(OH)](2-)HYDROGENPHOSPHATE IONhydrogen phosphate[P(OH)O3](2-)HPO4(2-)phosphateINORGANIC PHOSPHATE GROUPChEBI43474Reactome DB_ID: 2116061PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 98513871EQUAL745EQUALReactome Database ID Release 759880032Database 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=9880032ReactomeR-RNO-20460931Reactome 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-RNO-2046093.1Prior to this reaction all the enzymes involved in the desaturation and elongation of linoleic acid are located in the ER, but for this last step tetracosapentaenoyl-CoA must be transferred to the peroxisomes for partial beta-oxidation to docosapentaenoyl-CoA (DPA-CoA, 4,7,10,13,16-22:5(n-6)) (Su et al. 2001).9684854Pubmed1998Analysis of the putative role of 24-carbon polyunsaturated fatty acids in the biosynthesis of docosapentaenoic (22:5n-6) and docosahexaenoic (22:6n-3) acidsInfante, JPHuszagh, VAFEBS Lett 431:1-6inferred by electronic annotationIEAGOIEAReactome Database ID Release 759929866Database 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=9929866ReactomeR-RNO-20461051Reactome 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-RNO-2046105.1GO0043651GO biological processLinoleic acid (LA, 18:2(n-6)) is an omega-6 fatty acid obtained through diet, mainly from vegetable oils. Omega-6 fatty acids helps stimulate skin and hair growth, maintain bone health, regulate metabolism, and maintain the reproductive system. All the desaturation and elongation steps occur in the endoplasmic reticulum (ER) except for the final step which requires translocation to peroxisomes for partial beta-oxidation. The linoleic acid pathway involves the following steps: 18:2(n-6)-->18:3(n-6)--> 20:3(n-6)-->20:4(n-6)-->22:4(n-6)-->24:4(n-6)-->24:5(n-6)-->22:5(n-6). Two desaturation enzymes are involved in this process: delta-6 desaturase which converts 18:2(n-6) to 18:3 (n-6) and 24:4(n-6) to 24:5(n-6) respectively, and delta-5 desaturase which converts 20:3(n-6) to 20:4(n-6). (Sprecher 2002).10903473Pubmed2000Metabolism of highly unsaturated n-3 and n-6 fatty acidsSprecher, HBiochim Biophys Acta 1486:219-31inferred by electronic annotationIEAGOIEAReactome Database ID Release 759929868Database 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=9929868ReactomeR-RNO-20461041Reactome 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-RNO-2046104.1GO0033559GO biological processThere are two major classes of polyunsaturated fatty acids (PUFAs): the omega-3 (n-3) and the omega-6 (n-6) fatty acids, where the number corresponds to the position of the first double bond proximate to the methyl end of the fatty acid. Omega-3 and omega-6 fatty acids are considered essential fatty acids. Humans cannot synthesize them, instead they are supplied through diet. Linoleic acid (LA, 18:2(n-6)), a major component of omega-6 fatty acids and alpha-linolenic acid (ALA, 18:2(n-3)) a major component of omega-3 fatty acids are the two main dietary essential fatty acids (EFAs) in humans. ALA and LA obtained from diet are converted in the body into their longer chain and more unsaturated omega-3 and omega-6 products by a series of desaturation and elongation steps. Metabolism of ALA and LA to their corresponding products is mediated via common enzyme systems. In humans ALA is finally converted to docosahexaenoic acid (DHA, C22:6(n-3)), and LA is converted to docosapentaenoic acid (DPA, C22:5(n-6)). The intermediary omega-3 and omega-6 series fatty acids play a significant role in health and disease by generating potent modulatory molecules for inflammatory responses, including eicosanoids (prostaglandins, and leukotrienes), and cytokines (interleukins) and affecting the gene expression of various bioactive molecules (Kapoor & Huang 2006, Sprecher 2002, Burdge 2006).inferred by electronic annotationIEAGOIEA