title: Identification of genes and pathways involved in the synthesis of Mead acid (20:3n-9), an indicator of essential fatty acid deficiency.
abstract: In mammals, 5,8,11-eicosatrienoic acid (Mead acid, 20:3n-9) is synthesized from oleic acid during a state of essential fatty acid deficiency (EFAD). Mead acid is thought to be produced by the same enzymes that synthesize arachidonic acid and eicosapentaenoic acid, but the genes and the pathways involved in the conversion of oleic acid to Mead acid have not been fully elucidated. The levels of polyunsaturated fatty acids in cultured cells are generally very low compared to those in mammalian tissues. In this study, we found that cultured cells, such as NIH3T3 and Hepa1-6 cells, have significant levels of Mead acid, indicating that cells in culture are in an EFAD state under normal culture conditions. We then examined the effect of siRNA-mediated knockdown of fatty acid desaturases and elongases on the level of Mead acid, and found that knockdown of Elovl5, Fads1, or Fads2 decreased the level of Mead acid. This and the measured levels of possible intermediate products for the synthesis of Mead acid such as 18:2n-9, 20:1n-9 and 20:2n-9 in the knocked down cells indicate two pathways for the synthesis of Mead acid: pathway 1) 18:1n-9→(Fads2)→18:2n-9→(Elovl5)→20:2n-9→(Fads1)→20:3n-9 and pathway 2) 18:1n-9→(Elovl5)→20:1n-9→(Fads2)→20:2n-9→(Fads1)→20:3n-9.
authors.affiliation: Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo 112-8610, Japan.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ichi
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.forename: Yuka
authors.initials: Y
authors.lastname: Arita
authors.forename: Shizuka
authors.initials: S
authors.lastname: Haga
authors.forename: Kotoko
authors.initials: K
authors.lastname: Arisawa
authors.forename: Misato
authors.initials: M
authors.lastname: Yamano
authors.forename: Mana
authors.initials: M
authors.lastname: Nagase
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D000081031:Fatty Acid Elongases; D005228:Fatty Acids, Essential / Q000096:biosynthesis / Q000172:deficiency*; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells
chemical_list: D015415:Biomarkers; D005228:Fatty Acids, Essential; D044943:Fatty Acid Desaturases; D000123:Acetyltransferases; C581235:Elovl5 protein, mouse; D000081031:Fatty Acid Elongases; D015126:8,11,14-Eicosatrienoic Acid; C010944:mead acid
keywords: AA; ALA; Arachidonic acid; DHA; Docosahexaenoic acid; EFAD; EFAs; EPA; Eicosapentaenoic acid; Elongation of very long chain fatty acids; Elovl; Elovl5; Essential fatty acid deficiency; Essential fatty acids; FBS; Fads; Fatty acid desaturases; Fetal bovine serum; LA; Linoleic acid; Mead acid; PUFAs; Polyunsaturated fatty acid; Polyunsaturated fatty acids; α-Linolenic acid