title: The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells.
abstract: Docosahexaenoic acid (DHA) is a Δ4-desaturated C22 fatty acid and the limiting highly unsaturated fatty acid (HUFA) in neural tissue. The biosynthesis of Δ4-desaturated docosanoid fatty acids 22:6n-3 and 22:5n-6 are believed to proceed via a circuitous biochemical pathway requiring repeated use of a fatty acid desaturase 2 (FADS2) protein to perform Δ6 desaturation on C24 fatty acids in the endoplasmic reticulum followed by 1 round of β-oxidation in the peroxisomes. We demonstrate here that the FADS2 gene product can directly Δ4-desaturate 22:5n-3→22:6n-3 (DHA) and 22:4n-6→22:5n-6. Human MCF-7 cells lacking functional FADS2-mediated Δ6-desaturase were stably transformed with FADS2, FADS1, or empty vector. When incubated with 22:5n-3 or 22:4n-6, FADS2 stable cells produce 22:6n-3 or 22:5n-6, respectively. Similarly, FADS2 stable cells when incubated with d5-18:3n-3 show synthesis of d5-22:6n-3 with no labeling of 24:5n-3 or 24:6n-3 at 24 h. Further, both C24 fatty acids are shown to be products of the respective C22 fatty acids via elongation. Our results demonstrate that the FADS2 classical transcript mediates direct Δ4 desaturation to yield 22:6n-3 and 22:5n-6 in human cells, as has been widely shown previously for desaturation by fish and many other organisms.
authors.affiliation: *Division of Nutritional Sciences and Department of Food Science, Cornell University, Ithaca, New York, USA; and Department of Marine Food Science and Technology, Gangneung-Wonju National University, South Korea.
authors.forename: Hui Gyu
authors.initials: HG
authors.lastname: Park
authors.affiliation: *Division of Nutritional Sciences and Department of Food Science, Cornell University, Ithaca, New York, USA; and Department of Marine Food Science and Technology, Gangneung-Wonju National University, South Korea.
authors.forename: Woo Jung
authors.initials: WJ
authors.lastname: Park
authors.affiliation: *Division of Nutritional Sciences and Department of Food Science, Cornell University, Ithaca, New York, USA; and Department of Marine Food Science and Technology, Gangneung-Wonju National University, South Korea jtb4@cornell.edu ksk25@cornell.edu.
authors.forename: Kumar S D
authors.initials: KS
authors.lastname: Kothapalli
authors.affiliation: *Division of Nutritional Sciences and Department of Food Science, Cornell University, Ithaca, New York, USA; and Department of Marine Food Science and Technology, Gangneung-Wonju National University, South Korea jtb4@cornell.edu ksk25@cornell.edu.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
mesh_terms: D000818:Animals; D002384:Catalysis; D045744:Cell Line, Tumor; D000090943:Delta-5 Fatty Acid Desaturase; D004281:Docosahexaenoic Acids / Q000096:biosynthesis* / Q000235:genetics; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D010215:Papio
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human; C026219:docosapentaenoic acid
keywords: metabolism; nutrition; polyunsaturated fatty acids; Δ6 desaturation