Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Alpha Linolenic Acid and Linoleic Acid Metabolism
Homo sapiens
Metabolic Pathway
Created: 2013-08-01
Last Updated: 2023-10-12
Linoleic acid (LNA) is a polyunsaturated fatty acid (PUFA) precursor to the longer n−6 fatty acids commonly known as omega-6 fatty acids. Omega-6 fatty acids are characterized by a carbon-carbon double bond at the sixth carbon from the methyl group. Similarly, the PUFA alpha-linoleic acid (ALA) is the precursor to n-3 fatty acids known as omega-3 fatty acids which is characterized by a carbon-carbon double bond at the third carbon from the methyl group.
Both LNA and ALA are essential dietary requirements for all mammals since they cannot be synthesized natively in the body. Both undergo a series of similar conversions to reach their final fatty acid form. LNA enters the cell and is catalyzed to gamma-linolenic acid (GLA) by acyl-CoA 6-desaturase (delta-6-desaturase/fatty acid desaturase 2). GLA is then converted to dihomo-gammalinolenic acid (DGLA) by elongation of very long chain fatty acids protein 5 (ELOVL5). DGLA is then converted to arachidonic acid (AA) by acyl-CoA (8-3)-desaturase (delta-5-desaturase/fatty acid desaturase 1). Arachidonic acid is then converted to a series of short lived metabolites called eicosanoids before finally reaching it's final fatty acid form.
References
Alpha Linolenic Acid and Linoleic Acid Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (5th ed.) (2008) Amsterdam; Boston: Elsevier.
Stark AH, Reifen R, Crawford MA: Past and Present Insights on Alpha-linolenic Acid and the Omega-3 Fatty Acid Family. Crit Rev Food Sci Nutr. 2016 Oct 25;56(14):2261-7. doi: 10.1080/10408398.2013.828678.
Pubmed: 25774650
Barcelo-Coblijn G, Murphy EJ: Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels. Prog Lipid Res. 2009 Nov;48(6):355-74. doi: 10.1016/j.plipres.2009.07.002. Epub 2009 Jul 18.
Pubmed: 19619583
Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N Jr: Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res. 2001 Aug;42(8):1257-65.
Pubmed: 11483627
Cho HP, Nakamura M, Clarke SD: Cloning, expression, and fatty acid regulation of the human delta-5 desaturase. J Biol Chem. 1999 Dec 24;274(52):37335-9. doi: 10.1074/jbc.274.52.37335.
Pubmed: 10601301
Baker EJ, Miles EA, Burdge GC, Yaqoob P, Calder PC: Metabolism and functional effects of plant-derived omega-3 fatty acids in humans. Prog Lipid Res. 2016 Oct;64:30-56. doi: 10.1016/j.plipres.2016.07.002. Epub 2016 Aug 3.
Pubmed: 27496755
Domenichiello AF, Kitson AP, Bazinet RP: Is docosahexaenoic acid synthesis from alpha-linolenic acid sufficient to supply the adult brain? Prog Lipid Res. 2015 Jul;59:54-66. doi: 10.1016/j.plipres.2015.04.002. Epub 2015 Apr 25.
Pubmed: 25920364
Horrobin DF: Fatty acid metabolism in health and disease: the role of delta-6-desaturase. Am J Clin Nutr. 1993 May;57(5 Suppl):732S-736S; discussion 736S-737S. doi: 10.1093/ajcn/57.5.732S.
Pubmed: 8386433
Cho HP, Nakamura MT, Clarke SD: Cloning, expression, and nutritional regulation of the mammalian Delta-6 desaturase. J Biol Chem. 1999 Jan 1;274(1):471-7. doi: 10.1074/jbc.274.1.471.
Pubmed: 9867867
Marquardt A, Stohr H, White K, Weber BH: cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics. 2000 Jun 1;66(2):175-83. doi: 10.1006/geno.2000.6196.
Pubmed: 10860662
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Di Gregorio E, Borroni B, Giorgio E, Lacerenza D, Ferrero M, Lo Buono N, Ragusa N, Mancini C, Gaussen M, Calcia A, Mitro N, Hoxha E, Mura I, Coviello DA, Moon YA, Tesson C, Vaula G, Couarch P, Orsi L, Duregon E, Papotti MG, Deleuze JF, Imbert J, Costanzi C, Padovani A, Giunti P, Maillet-Vioud M, Durr A, Brice A, Tempia F, Funaro A, Boccone L, Caruso D, Stevanin G, Brusco A: ELOVL5 mutations cause spinocerebellar ataxia 38. Am J Hum Genet. 2014 Aug 7;95(2):209-17. doi: 10.1016/j.ajhg.2014.07.001. Epub 2014 Jul 24.
Pubmed: 25065913
Leonard AE, Bobik EG, Dorado J, Kroeger PE, Chuang LT, Thurmond JM, Parker-Barnes JM, Das T, Huang YS, Mukerji P: Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. Biochem J. 2000 Sep 15;350 Pt 3:765-70.
Pubmed: 10970790
Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A: Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001 Mar;11(3):422-35. doi: 10.1101/gr.gr1547r.
Pubmed: 11230166
Leonard AE, Kelder B, Bobik EG, Chuang LT, Parker-Barnes JM, Thurmond JM, Kroeger PE, Kopchick JJ, Huang YS, Mukerji P: cDNA cloning and characterization of human Delta5-desaturase involved in the biosynthesis of arachidonic acid. Biochem J. 2000 May 1;347 Pt 3:719-24.
Pubmed: 10769175
Aldahmesh MA, Mohamed JY, Alkuraya HS, Verma IC, Puri RD, Alaiya AA, Rizzo WB, Alkuraya FS: Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. Am J Hum Genet. 2011 Dec 9;89(6):745-50. doi: 10.1016/j.ajhg.2011.10.011. Epub 2011 Nov 17.
Pubmed: 22100072
Rivolta C, Ayyagari R, Sieving PA, Berson EL, Dryja TP: Evaluation of the ELOVL4 gene in patients with autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. Mol Vis. 2003 Feb 18;9:49-51.
Pubmed: 12592226
Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, Martin C, Meloche C, Gravel M, Drouin CA, Rouleau GA, Nguyen DK, Cossette P: Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. JAMA Neurol. 2014 Apr;71(4):470-5. doi: 10.1001/jamaneurol.2013.6337.
Pubmed: 24566826
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Settings