RRC ID 68797
Author Ichi I, Kono N, Arita Y, Haga S, Arisawa K, Yamano M, Nagase M, Fujiwara Y, Arai H.
Title Identification of genes and pathways involved in the synthesis of Mead acid (20:3n-9), an indicator of essential fatty acid deficiency.
Journal Biochim Biophys Acta
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.
Volume 1841(1)
Pages 204-13
Published 2014-1-1
DOI 10.1016/j.bbalip.2013.10.013
PII S1388-1981(13)00236-9
PMID 24184513
MeSH 8,11,14-Eicosatrienoic Acid / analogs & derivatives* 8,11,14-Eicosatrienoic Acid / genetics 8,11,14-Eicosatrienoic Acid / metabolism Acetyltransferases / genetics Acetyltransferases / metabolism* Animals Biomarkers / metabolism Fatty Acid Desaturases / genetics Fatty Acid Desaturases / metabolism* Fatty Acid Elongases Fatty Acids, Essential / biosynthesis Fatty Acids, Essential / deficiency* Gene Knockdown Techniques Male Mice NIH 3T3 Cells
Resource
Human and Animal Cells Hepa 1-6(RCB1638)