Identification of genes and pathways involved in the synthesis of Mead acid (20:3n 鈭?#xa0;9), an indicator of essential fatty acid deficiency

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• 作者：Ikuyo Ichi ; Nozomu Kono ; Yuka Arita ; Shizuka Haga ; Kotoko Arisawa ; Misato Yamano ; Mana Nagase ; Yoko Fujiwara ; Hiroyuki Arai
• 关键词：AA ; Arachidonic acid ; ALA ; 伪-Linolenic acid ; DHA ; Docosahexaenoic acid ; EFAs ; Essential fatty acids ; EFAD ; Essential fatty acid deficiency ; Elovl ; Elongation of very long chain fatty acids ; EPA ; Eicosapentaenoic acid ; Fads ; Fatty acid desaturases ; FBS ; Fetal bovine serum ; LA ; Linoleic acid ; PUFAs ; Polyunsaturated fatty acids
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：January, 2014
• 年：2014
• 卷：1841
• 期：1
• 页码：204-213
• 全文大小：1073 K

文摘

In mammals, 5,8,11-eicosatrienoic acid (Mead acid, 20:3n 鈭?#xA0;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 鈭?#xA0;9, 20:1n 鈭?#xA0;9 and 20:2n 鈭?#xA0;9 in the knocked down cells indicate two pathways for the synthesis of Mead acid: pathway 1) 18:1n 鈭?#xA0;9 鈫?#xA0;(Fads2) 鈫?#xA0;18:2n 鈭?#xA0;9 鈫?#xA0;(Elovl5) 鈫?#xA0;20:2n 鈭?#xA0;9 鈫?#xA0;(Fads1) 鈫?#xA0;20:3n 鈭?#xA0;9 and pathway 2) 18:1n 鈭?#xA0;9 鈫?#xA0;(Elovl5) 鈫?#xA0;20:1n 鈭?#xA0;9 鈫?#xA0;(Fads2) 鈫?#xA0;20:2n 鈭?#xA0;9 鈫?#xA0;(Fads1) 鈫?#xA0;20:3n 鈭?#xA0;9.