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Pathway Description
Alpha Linolenic Acid and Linoleic Acid Metabolism
Homo sapiens
Metabolic Pathway
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
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