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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp alpha-linolenic acid (ALA) metabolism alpha-linolenic acid (ALA) metabolism This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 6.2.1.3 Activation of alpha-linolenic acid to alpha-linolenoyl-CoA Activation of alpha-linolenic acid to alpha-linolenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046056 1 endoplasmic reticulum lumen GO 0005788 alpha-linolenic acid [ChEBI:27432] alpha-linolenic acid Reactome //www.joaskin.com ChEBI 27432 Reactome DB_ID: 162743 1 coenzyme A [ChEBI:15346] coenzyme A ChEBI 15346 Reactome DB_ID: 211579 1 endoplasmic reticulum membrane GO 0005789 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 2046049 1 diphosphoric acid [ChEBI:29888] diphosphoric acid ChEBI 29888 Reactome DB_ID: 2046064 1 adenosine 5'-monophosphate [ChEBI:16027] adenosine 5'-monophosphate ChEBI 16027 Reactome DB_ID: 2046062 1 alpha-linolenoyl-CoA [ChEBI:51985] alpha-linolenoyl-CoA cis,cis-9,12-octadecadienoyl-CoA cis-Delta(9,12)-octadecadienoyl-CoA cis-Delta(9,12)-octadecadienoyl-coenzyme A cis,cis-9,12-octadecadienoyl-coenzyme A alpha-linolenoyl-coenzyme A cis,cis-linoleoyl-CoA cis,cis-linoleoyl-coenzyme A ChEBI 51985 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10266437 ACSL1 [endoplasmic reticulum membrane] ACSL1 Reactome DB_ID: 10225294 1 UniProt:B8JK22 acsl1a Danio rerio NCBI Taxonomy 7955 UniProt B8JK22 Chain Coordinates 1 EQUAL 698 EQUAL Reactome DB_ID: 217314 1 magnesium(2+) [ChEBI:18420] magnesium(2+) ChEBI 18420 Reactome Database ID Release 77 10266437 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266437 Reactome R-DRE-2046075 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046075.1 GO 0004467 GO molecular function Reactome Database ID Release 77 10266438 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266438 Reactome Database ID Release 77 10266440 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266440 Reactome R-DRE-2046085 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046085.1 In 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. 7061494 Pubmed 1982 Discovery of an arachidonoyl coenzyme A synthetase in human platelets Wilson, DB Prescott, SM Majerus, PW J Biol Chem 257:3510-5 978-0-12-417762-8 ISBN 2003 Docosahexaenoic acid Biosketch, Kohlmeier Nutrient Metabolism (Book): 164-175 inferred by electronic annotation IEA GO IEA 1.14.19.3 Desaturation of alpha-linoleoyl-CoA to Stearidonoyl-CoA Desaturation of alpha-linoleoyl-CoA to Stearidonoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046062 1 Reactome DB_ID: 194697 2 NADH(2-) [ChEBI:57945] NADH(2-) NADH dianion adenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NADH ChEBI 57945 Reactome DB_ID: 113534 1 dioxygen [ChEBI:15379] dioxygen ChEBI 15379 Reactome DB_ID: 2046052 1 (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA [ChEBI:63545] (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA ChEBI 63545 Reactome DB_ID: 113519 2 water [ChEBI:15377] water ChEBI 15377 Reactome DB_ID: 194653 2 NAD(1-) [ChEBI:57540] NAD(1-) NAD(+) adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NAD anion ChEBI 57540 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10266432 UniProt:Q9DEX7 fads2 UniProt Q9DEX7 1 EQUAL 444 EQUAL GO 0016213 GO molecular function Reactome Database ID Release 77 10266433 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266433 Reactome Database ID Release 77 10266435 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266435 Reactome R-DRE-2046084 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046084.1 Alpha-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). 12562861 Pubmed 2003 Regulation of human delta-6 desaturase gene transcription: identification of a functional direct repeat-1 element Tang, C Cho, HP Nakamura, MT Clarke, SD J Lipid Res 44:686-95 12713571 Pubmed 2003 Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity Ge, L Gordon, JS Hsuan, C Stenn, K Prouty, SM J Invest Dermatol 120:707-14 8386433 Pubmed 1993 Fatty acid metabolism in health and disease: the role of delta-6-desaturase Horrobin, DF Am J Clin Nutr 57:732S-736S; discussion 736S-737S 1346092 Pubmed 1992 Comparison 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 rats Yamazaki, K Fujikawa, M Hamazaki, T Yano, S Shono, T Biochim Biophys Acta 1123:18-26 11988075 Pubmed 2002 The same rat Delta6-desaturase not only acts on 18- but also on 24-carbon fatty acids in very-long-chain polyunsaturated fatty acid biosynthesis d'Andréa, S Guillou, H Jan, S Catheline, D Thibault, JN Bouriel, M Rioux, V Legrand, P Biochem J 364:49-55 19056654 Pubmed 2009 Dietary stearidonic acid is a long chain (n-3) polyunsaturated fatty acid with potential health benefits Whelan, J J Nutr 139:5-10 inferred by electronic annotation IEA GO IEA Elongation of stearidonoyl-CoA to eicosatetraenoyl-CoA Elongation of stearidonoyl-CoA to eicosatetraenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046052 1 Reactome DB_ID: 113601 2 NADPH [ChEBI:16474] NADPH TPNH ChEBI 16474 Reactome DB_ID: 2046066 1 malonyl-CoA [ChEBI:15531] malonyl-CoA ChEBI 15531 Reactome DB_ID: 159751 1 carbon dioxide [ChEBI:16526] carbon dioxide ChEBI 16526 Reactome DB_ID: 113519 1 Reactome DB_ID: 113564 2 NADP(+) [ChEBI:18009] NADP(+) ChEBI 18009 Reactome DB_ID: 2046051 1 (8Z,11Z,14Z,17Z)-icosatetraenoyl-CoA [ChEBI:63542] (8Z,11Z,14Z,17Z)-icosatetraenoyl-CoA ChEBI 63542 Reactome DB_ID: 162743 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10245475 ELOVL1,2,3,5 [endoplasmic reticulum membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity elovl5 [endoplasmic reticulum membrane] elovl2 [endoplasmic reticulum membrane] elovl1b [endoplasmic reticulum membrane] elovl6l [endoplasmic reticulum membrane] UniProt Q8AX86 UniProt A3KP14 UniProt A0A0R4IT00 UniProt B8JK95 GO 0009922 GO molecular function Reactome Database ID Release 77 10245476 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10245476 Reactome Database ID Release 77 10266445 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266445 Reactome R-DRE-2046088 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046088.1 SDA-CoA(6、9、12、15-18:4 (n))正在迅速拉长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). 14636670 Pubmed 2004 Elongation of long-chain fatty acids Leonard, AE Pereira, SL Sprecher, H Huang, YS Prog Lipid Res 43:36-54 10899997 Pubmed 2000 Identification and characterization of an enzyme involved in the elongation of n-6 and n-3 polyunsaturated fatty acids Parker-Barnes, JM Das, T Bobik, E Leonard, AE Thurmond, JM Chaung, LT Huang, YS Mukerji, P Proc Natl Acad Sci U S A 97:8284-9 12716664 Pubmed 2003 Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids James, MJ Ursin, VM Cleland, LG Am J Clin Nutr 77:1140-5 inferred by electronic annotation IEA GO IEA Elongation of eicosapentaenoyl-CoA to docosapentaenoyl-CoA Elongation of eicosapentaenoyl-CoA to docosapentaenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046059 1 (5Z,8Z,11Z,14Z,17Z)-icosapentaenoyl-CoA [ChEBI:63539] (5Z,8Z,11Z,14Z,17Z)-icosapentaenoyl-CoA ChEBI 63539 Reactome DB_ID: 113601 2 Reactome DB_ID: 2046066 1 Reactome DB_ID: 159751 1 Reactome DB_ID: 113519 1 Reactome DB_ID: 113564 2 Reactome DB_ID: 2046057 1 (7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA [ChEBI:63541] (7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA ChEBI 63541 Reactome DB_ID: 162743 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10266425 ELOVL5/ELOVL2 [endoplasmic reticulum membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity elovl5 [endoplasmic reticulum membrane] elovl2 [endoplasmic reticulum membrane] Reactome Database ID Release 77 10266426 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266426 Reactome Database ID Release 77 10266462 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266462 Reactome R-DRE-2046100 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046100.1 Eicosapentaenoyl-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). 8832760 Pubmed 1996 Docosapentaenoic 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 vitro Kanayasu-Toyoda, T Morita, I Murota, S Prostaglandins Leukot Essent Fatty Acids 54:319-25 12323085 Pubmed 2002 Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men* Burdge, Graham C Jones, AE Wootton, SA Br J Nutr 88:355-63 12323090 Pubmed 2002 eicosapentae转换的亚麻酸noic, docosapentaenoic and docosahexaenoic acids in young women Burdge, Graham C Wootton, SA Br J Nutr 88:411-20 20655949 Pubmed 2011 Docosapentaenoic acid (22:5n-3): a review of its biological effects Kaur, G Cameron-Smith, D Garg, M Sinclair, AJ Prog Lipid Res 50:28-34 inferred by electronic annotation IEA GO IEA Elongation of docosapentaenoyl-CoA to tetracosapentaenoyl-CoA Elongation of docosapentaenoyl-CoA to tetracosapentaenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 113601 2 Reactome DB_ID: 2046057 1 Reactome DB_ID: 2046066 1 Reactome DB_ID: 159751 1 Reactome DB_ID: 113519 1 Reactome DB_ID: 113564 2 Reactome DB_ID: 2046065 1 (9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoA [ChEBI:63543] (9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoA ChEBI 63543 Reactome DB_ID: 162743 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10245465 UniProt:A3KP14 elovl2 1 EQUAL 296 EQUAL Reactome Database ID Release 77 10266446 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266446 Reactome Database ID Release 77 10266448 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266448 Reactome R-DRE-2046090 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046090.1 Docosapentaenoyl-CoA is elongated to tetracosapentaenoyl-CoA (9,12,15,18,21-24:5(n-3)) by the enzyme ELOVL2. 1834642 Pubmed 1991 The 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-desaturase Voss, A Reinhart, M Sankarappa, S Sprecher, H J Biol Chem 266:19995-20000 inferred by electronic annotation IEA GO IEA 7.6.2.4 Translocation of tetracosahexaenoyl-CoA to peroxisomes Translocation of tetracosahexaenoyl-CoA to peroxisomes This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046054 1 (6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA [ChEBI:63540] (6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA ChEBI 63540 Reactome DB_ID: 211579 1 Reactome DB_ID: 211606 1 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5'-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 Reactome DB_ID: 2046047 1 peroxisomal matrix GO 0005782 Reactome DB_ID: 426639 1 1-phosphatidyl-1D-myo-inositol [ChEBI:16749] 1-phosphatidyl-1D-myo-inositol ChEBI 16749 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10237304 peroxisomal membrane GO 0005778 UniProt:F1RBC8 abcd1 UniProt F1RBC8 1 EQUAL 745 EQUAL GO 0005324 GO molecular function Reactome Database ID Release 77 10266441 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266441 Reactome Database ID Release 77 10266443 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266443 Reactome R-DRE-2046087 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046087.1 The 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). 12897190 Pubmed 2003 Studies on the metabolic fate of n-3 polyunsaturated fatty acids Ferdinandusse, Sacha Denis, Simone Dacremont, Georges Wanders, Ronald J A J Lipid Res 44:1992-7 11500517 Pubmed 2001 Peroxisomal straight-chain Acyl-CoA oxidase and D-bifunctional protein are essential for the retroconversion step in docosahexaenoic acid synthesis Su, HM Moser, AB Moser, HW Watkins, PA J临床生物化学276:38115-20 8656081 Pubmed 1995 二十二碳六烯酸在人体皮肤合成纤维blasts involves peroxisomal retroconversion of tetracosahexaenoic acid Moore, SA Hurt, E Yoder, E Sprecher, H Spector, AA J Lipid Res 36:2433-43 12324224 Pubmed 2002 The roles of anabolic and catabolic reactions in the synthesis and recycling of polyunsaturated fatty acids Sprecher, H Prostaglandins Leukot Essent Fatty Acids 67:79-83 8663162 Pubmed 1996 Regulation of the biosynthesis of 4,7,10,13,16,19-docosahexaenoic acid Luthria, DL Mohammed, BS Sprecher, H J Biol Chem 271:16020-5 inferred by electronic annotation IEA GO IEA 1.3.3.6 Oxidation of tetracosapentaenoyl-CoA to delta2-tetracosaheptaenoyl-CoA Oxidation of tetracosapentaenoyl-CoA to delta2-tetracosaheptaenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 113535 1 Reactome DB_ID: 2046047 1 Reactome DB_ID: 2066767 1 (2 e,6Z,9Z,12Z,15Z,18Z,21Z)-tetracosaheptaenoyl-CoA [ChEBI:65139] (2 e,6Z,9Z,12Z,15Z,18Z,21Z)-tetracosaheptaenoyl-CoA ChEBI 65139 Reactome DB_ID: 113575 1 hydrogen peroxide [ChEBI:16240] hydrogen peroxide ChEBI 16240 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10237825 ACOX1 dimer [peroxisomal matrix] ACOX1 dimer Reactome DB_ID: 10237823 2 ACOX1:FAD complex [peroxisomal matrix] ACOX1:FAD complex Reactome DB_ID: 141335 1 FAD [ChEBI:16238] FAD Flavin adenine dinucleotide ChEBI 16238 Reactome DB_ID: 10237821 1 UniProt:F1R071 acox1 UniProt F1R071 1 EQUAL 660 EQUAL Reactome Database ID Release 77 10237823 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10237823 Reactome R-DRE-390237 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-390237.1 Reactome Database ID Release 77 10237825 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10237825 Reactome R-DRE-390232 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-390232.1 GO 0003997 GO molecular function Reactome Database ID Release 77 10237826 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10237826 Reactome Database ID Release 77 10266716 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266716 Reactome R-DRE-2066787 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2066787.1 Retroconversion 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). 11734571 Pubmed 2001 Identification of the peroxisomal beta-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid Ferdinandusse, Sacha Denis, Simone Mooijer, PA Zhang, Z Reddy, Janardan K Spector, AA Wanders, Ronald J A J Lipid Res 42:1987-95 inferred by electronic annotation IEA GO IEA 4.2.1.74 Hydration of delta2-tetracosaheptaenoyl-CoA to 3-hydroxy tetracosahexaenoyl-CoA Hydration of delta2-tetracosaheptaenoyl-CoA to 3-hydroxy tetracosahexaenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 141343 1 Reactome DB_ID: 2066767 1 Reactome DB_ID: 2066766 1 (6Z,9Z,12Z,15Z,18Z,21Z)-3-hydroxytetracosahexaenoyl-CoA [ChEBI:65130] (6Z,9Z,12Z,15Z,18Z,21Z)-3-hydroxytetracosahexaenoyl-CoA ChEBI 65130 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10222690 HSD17B4 dimer [peroxisomal matrix] HSD17B4 dimer Reactome DB_ID: 10222688 2 UniProt:Q8AYH1 hsd17b4 UniProt Q8AYH1 1 EQUAL 736 EQUAL Reactome Database ID Release 77 10222690 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10222690 Reactome R-DRE-389999 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-389999.1 GO 0016508 GO molecular function Reactome Database ID Release 77 10237800 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10237800 Reactome Database ID Release 77 10266708 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266708 Reactome R-DRE-2066778 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2066778.1 Delta2-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. 9089413 Pubmed 1997 Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein Jiang, LL Miyazawa, S Souri, M Hashimoto, Takashi J Biochem 121:364-9 inferred by electronic annotation IEA GO IEA 4.2.1.74 Dehydrogenation of 3-hydroxy tetracosahexaenoyl-CoA Dehydrogenation of 3-hydroxy tetracosahexaenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2066766 1 Reactome DB_ID: 2066762 1 (6Z,9Z,12Z,15Z,18Z,21Z)-3-oxotetracosahexaenoyl-CoA [ChEBI:65131] (6Z,9Z,12Z,15Z,18Z,21Z)-3-oxotetracosahexaenoyl-CoA ChEBI 65131 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10222690 Reactome Database ID Release 77 10266712 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266712 Reactome R-DRE-2066780 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2066780.1 3-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 annotation IEA GO IEA 2.3.1.176 Formation of DHA-CoA catalysed by sterol carrier protein X (SCPx) Formation of DHA-CoA catalysed by sterol carrier protein X (SCPx) This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2066762 1 Reactome DB_ID: 193514 1 Reactome DB_ID: 2066765 1 (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA [ChEBI:65132] (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA ChEBI 65132 Reactome DB_ID: 192314 1 propionyl-CoA [ChEBI:15539] propionyl-CoA ChEBI 15539 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10222697 UniProt:Q6P4V5 scp2a UniProt Q6P4V5 1 EQUAL 547 EQUAL GO 0050632 GO molecular function Reactome Database ID Release 77 10222698 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10222698 Reactome Database ID Release 77 10266714 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266714 Reactome R-DRE-2066781 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2066781.1 The final step in the beta-oxidation process is the thiolytic cleavage of 1-(3-oxo-6Z,9Z,12Z,15Z,18Z,21Z-tetracosahexaenoyl)-CoA to form docosahexaenoyl-CoA (DHA-CoA). This step is catalysed by both sterol carrier protein X (SCPx) (this reaction) and the classic 3-ketoacyl-CoA thiolase (Ferdinandusse et al. 2001). inferred by electronic annotation IEA GO IEA 2.8.3.8 Formation of DHA-CoA catalysed by 3-ketoacyl-CoA thiolase Formation of DHA-CoA catalysed by 3-ketoacyl-CoA thiolase This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2066762 1 Reactome DB_ID: 193514 1 Reactome DB_ID: 2066765 1 Reactome DB_ID: 353123 1 acetyl-CoA [ChEBI:15351] acetyl-CoA ChEBI 15351 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10237810 UniProt:Q6GQN6 acaa1 UniProt Q6GQN6 27 EQUAL 424 EQUAL GO 0008775 GO molecular function Reactome Database ID Release 77 10266717 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266717 Reactome Database ID Release 77 10266719 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266719 Reactome R-DRE-2066788 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2066788.1 The final step in the beta-oxidation process is the thiolytic cleavage of 1-(3-oxo-6Z,9Z,12Z,15Z,18Z,21Z-tetracosahexaenoyl)-CoA to form docosahexaenoyl-CoA (DHA-CoA). This step is catalysed by both sterol carrier protein X (SCPx) and the classic 3-ketoacyl-CoA thiolase (this reaction) (Ferdinandusse et al. 2001). inferred by electronic annotation IEA GO IEA 3.1.2.1 Conversion 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.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2066765 1 Reactome DB_ID: 141343 1 Reactome DB_ID: 2066763 1 all-cis-docosa-4,7,10,13,16,19-hexaenoic acid [ChEBI:28125] all-cis-docosa-4,7,10,13,16,19-hexaenoic acid ChEBI 28125 Reactome DB_ID: 193514 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10222845 UniProt:Q5XJP9 acot8 UniProt Q5XJP9 1 EQUAL 319 EQUAL GO 0003986 GO molecular function Reactome Database ID Release 77 10237845 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10237845 Reactome Database ID Release 77 10266710 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266710 Reactome R-DRE-2066779 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2066779.1 DHA-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). 18538142 Pubmed 2008 Novel functions of acyl-CoA thioesterases and acyltransferases as auxiliary enzymes in peroxisomal lipid metabolism Hunt, MC Alexson, SE Prog Lipid Res 47:405-21 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10323484 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10323484 Reactome R-DRE-2046106 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046106.1 GO 0036109 GO biological process Alpha-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.

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). 16828546 Pubmed 2006 Metabolism of alpha-linolenic acid in humans Burdge, Graham C Prostaglandins Leukot Essent Fatty Acids 75:161-8 8443237 Pubmed 1993 Desaturation and chain elongation of n - 3 and n - 6 polyunsaturated fatty acids in the human CaCo-2 cell line Chen, Q Nilsson, A Biochim Biophys Acta 1166:193-201 inferred by electronic annotation IEA GO IEA Linoleic acid (LA) metabolism Linoleic acid (LA) metabolism This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp 6.2.1.3 Activation of linoleic acid to linoleoyl-CoA Activation of linoleic acid to linoleoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046044 1 linoleic acid [ChEBI:17351] linoleic acid ChEBI 17351 Reactome DB_ID: 162743 1 Reactome DB_ID: 211579 1 Reactome DB_ID: 2046063 1 linoleoyl-CoA [ChEBI:15530] linoleoyl-CoA ChEBI 15530 Reactome DB_ID: 2046049 1 Reactome DB_ID: 2046064 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10266437 Reactome Database ID Release 77 10266460 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266460 Reactome R-DRE-2046098 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046098.1 The 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). 20480548 Pubmed 2010 Acyl-coenzyme A synthetases in metabolic control Ellis, JM Frahm, JL Li, LO Coleman, RA Curr Opin Lipidol 21:212-7 18024425 Pubmed 2008 Very-long-chain acyl-CoA synthetases Watkins, PA J Biol Chem 283:1773-7 inferred by electronic annotation IEA GO IEA 1.14.19.3 Desaturation of Linoleoyl-CoA to gamma-linolenoyl-CoA Desaturation of Linoleoyl-CoA to gamma-linolenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046063 1 Reactome DB_ID: 194697 2 Reactome DB_ID: 113534 1 Reactome DB_ID: 113519 2 Reactome DB_ID: 2046042 1 gamma-linolenoyl-CoA [ChEBI:15508] gamma-linolenoyl-CoA ChEBI 15508 Reactome DB_ID: 194653 2 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10266432 1 EQUAL 444 EQUAL Reactome Database ID Release 77 10266456 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266456 Reactome R-DRE-2046096 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046096.1 The 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 annotation IEA GO IEA Elongation of gamma-lenolenoyl-CoA to dihomo-gamma-lenolenoyl-CoA Elongation of gamma-lenolenoyl-CoA to dihomo-gamma-lenolenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046042 1 Reactome DB_ID: 113601 2 Reactome DB_ID: 2046066 1 Reactome DB_ID: 159751 1 Reactome DB_ID: 2046045 1 all-cis-icosa-8,11,14-trienoyl-CoA [ChEBI:27979] all-cis-icosa-8,11,14-trienoyl-CoA ChEBI 27979 Reactome DB_ID: 113519 1 Reactome DB_ID: 113564 2 Reactome DB_ID: 162743 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10245475 Reactome Database ID Release 77 10266452 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266452 Reactome R-DRE-2046094 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046094.1 Gamma-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)).
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) 10970790 Pubmed 2000 Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids Leonard, AE Bobik, EG Dorado, J Kroeger, PE Chuang, LT Thurmond, JM Parker-Barnes, JM Das, T Huang, YS Mukerji, P Biochem J 350:765-70 1-893997-17-0 ISBN 2001 Antiatherogenic伽玛亚麻酸的潜力 Fan, YY Chapkin, RS Ramos, KS gamma-linolenic acid (Book): 169 9732298 Pubmed 1998 Importance of dietary gamma-linolenic acid in human health and nutrition Fan, YY Chapkin, RS J Nutr 128:1411-4 8609415 Pubmed 1996 Metabolism of gammalinolenic acid in human neutrophils Chilton-Lopez, T Surette, ME Swan, DD Fonteh, AN Johnson, MM Chilton, FH J Immunol 156:2941-7 17168669 Pubmed 2006 Gamma linolenic acid: an antiinflammatory omega-6 fatty acid Kapoor, R Huang, YS Curr Pharm Biotechnol 7:531-4 inferred by electronic annotation IEA GO IEA Elongation of arachidonyl-CoA to docosatetraenoyl-CoA Elongation of arachidonyl-CoA to docosatetraenoyl-CoA arachidonoyl-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.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 113601 2 Reactome DB_ID: 2046053 1 arachidonoyl-CoA [ChEBI:15514] arachidonoyl-CoA ChEBI 15514 Reactome DB_ID: 2046066 1 Reactome DB_ID: 2046060 1 (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA [ChEBI:63544] (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA ChEBI 63544 Reactome DB_ID: 159751 1 Reactome DB_ID: 113519 1 Reactome DB_ID: 162743 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10266425 Reactome Database ID Release 77 10266428 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266428 Reactome R-DRE-2046083 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046083.1 Arachidonyl-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). 20038752 Pubmed 2010 Adrenic acid metabolites as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors Kopf, PG Zhang, DX Gauthier, KM Nithipatikom, K Yi, XY Falck, JR Campbell, WB Hypertension 55:547-54 inferred by electronic annotation IEA GO IEA Elongation of docosatetraenoyl-CoA to tetracosatetraenoyl-CoA Elongation of docosatetraenoyl-CoA to tetracosatetraenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046060 1 Reactome DB_ID: 113601 2 Reactome DB_ID: 2046066 1 Reactome DB_ID: 159751 1 Reactome DB_ID: 2046048 1 (9Z,12Z,15Z,18Z)-tetracosatetraenoyl-CoA [ChEBI:63548] (9Z,12Z,15Z,18Z)-tetracosatetraenoyl-CoA ChEBI 63548 Reactome DB_ID: 113519 1 Reactome DB_ID: 162743 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10245465 1 EQUAL 296 EQUAL Reactome Database ID Release 77 10266454 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266454 Reactome R-DRE-2046095 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046095.1 Docosatetraenoyl-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. 9704073 Pubmed 1973 Fate of linoleic, arachidonic, and docosa-7,10,13,16-tetraenoic acids in rat testicles Ayala, S Gaspar, G Brenner, RR Peluffo, RO Kunau, W J Lipid Res 14:296-305 5411545 Pubmed 1970 The biosynthesis of delta-9,12,15,18-tetracosatetraenoic and of delta-6,9,12,15,18-tetracosapentaenoic acids by rat testes Bridges, RB Coniglio, JG J Biol Chem 245:46-9 inferred by electronic annotation IEA GO IEA 1.14.19.3 Desaturation of tetracosatetraenoyl-CoA to tetracosapentaenoyl-CoA Desaturation of tetracosatetraenoyl-CoA to tetracosapentaenoyl-CoA This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046048 1 Reactome DB_ID: 194697 2 Reactome DB_ID: 113534 1 Reactome DB_ID: 113519 2 Reactome DB_ID: 194653 2 Reactome DB_ID: 2046050 1 (6Z,9Z,12Z,15Z,18Z)-tetracosapentaenoyl-CoA [ChEBI:63546] (6Z,9Z,12Z,15Z,18Z)-tetracosapentaenoyl-CoA ChEBI 63546 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10266432 1 EQUAL 444 EQUAL Reactome Database ID Release 77 10266458 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266458 Reactome R-DRE-2046097 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046097.1 Tetracosatetraenoyl-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 annotation IEA GO IEA 7.6.2.4 Translocation of tetracosapentaenoyl-CoA to peroxisomes Translocation of tetracosapentaenoyl-CoA to peroxisomes This event has been computationally inferred from an event that has been demonstrated in another species.

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.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Reactome DB_ID: 2046050 1 Reactome DB_ID: 211579 1 Reactome DB_ID: 5228339 1 hydrogenphosphate [ChEBI:43474] hydrogenphosphate [PO3(OH)](2-) HYDROGENPHOSPHATE离子 hydrogen phosphate [P(OH)O3](2-) HPO4(2-) phosphate INORGANIC PHOSPHATE GROUP ChEBI 43474 Reactome DB_ID: 211606 1 Reactome DB_ID: 2046055 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10237304 1 EQUAL 745 EQUAL Reactome Database ID Release 77 10266450 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10266450 Reactome R-DRE-2046093 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046093.1 Prior 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). 9684854 Pubmed 1998 Analysis of the putative role of 24-carbon polyunsaturated fatty acids in the biosynthesis of docosapentaenoic (22:5n-6) and docosahexaenoic (22:6n-3) acids Infante, JP Huszagh, VA FEBS Lett 431:1-6 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10323480 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10323480 Reactome R-DRE-2046105 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046105.1 GO 0043651 GO biological process 亚油酸(洛杉矶,18:2 (n-6))是一种ω- 6脂肪酸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). 10903473 Pubmed 2000 Metabolism of highly unsaturated n-3 and n-6 fatty acids Sprecher, H Biochim Biophys Acta 1486:219-31 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 77 10323482 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10323482 Reactome R-DRE-2046104 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-2046104.1 GO 0033559 GO biological process There 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 annotation IEA GO IEA