Function analysis of Mead acid and its metabolism in essential fatty acid deficiency state

在哺乳动物中，5，8，11-二十碳三烯酸（米德酸，20：3 n-9）在必需脂肪酸缺乏（EFAD）状态期间由油酸合成。米德酸被认为是由合成花生四烯酸和二十碳五烯酸的相同酶产生的，但参与油酸转化为米德酸的基因和途径尚未完全阐明。在本研究中，我们发现培养的细胞，如NIH 3 T3细胞，具有显著水平的米德酸，表明培养中的细胞在正常培养条件下处于EFAD状态。然后，我们检查了siRNA介导的脂肪酸去饱和酶和延长酶的敲低对米德酸水平的影响，并发现Elov 15、Fads 1或Fads 2的敲低降低了米德酸的水平。这一点以及在敲低的细胞中测定的合成米德酸的可能中间产物如18：2n-9、20：1 n-9和20：2n-9的水平表明米德酸的合成有两条途径。

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. In this study, we found that the cultured cell, such as NIH3T3 cells, had 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.