Laboratoire de Biochimie et Nutrition Humaine, INRA USC 2012, Agrocampus Ouest, Rennes, France.
Biochimie. 2011 Jan;93(1):87-90. doi: 10.1016/j.biochi.2010.03.002. Epub 2010 Mar 11.
Since its identification in 2000, no function has been attributed to the Fatty Acid Desaturase 3 (Fads3) gene. This gene is located within the Fads cluster, which also contains Fads1 and Fads2, coding respectively for the Δ5- and Δ6- desaturases. Based on the sequence homology between these three genes, Fads3 may be a new fatty acid desaturase. It is thus essential to understand its involvement in Polyunsaturated Fatty Acid (PUFA) biosynthesis in order to improve our knowledge on lipid metabolism. Gene expression studies provided evidences on the specificity of Fads3 compared to Fads1 and Fads2, concerning the tissue distribution, alternative splicing and regulation. These works also identified possible physiological functions in which Fads3 could be involved. Thus, the Fads3 gene was transcripted in many tissues, and displayed a weak expression in the liver compared to other organs such as the lung or spleen. Fads3 was also showed to be a target gene for NK-κB, MYCN or p63 transcription factors and could consequently be involved in cell survival mechanisms. Polymorphism analysis underlined the possible implication of Fads3 in lipid homeostasis, particularly by modulating cholesterol and triglyceride plasma levels. In terms of proteins, FADS3 has been recently described in rodents. One of the identified isoforms may display the classical structure of a fatty acid desaturase but no enzymatic activity has been observed yet. Therefore, it is essential to consider the desaturase diversity in terms of catalysis and substrates to elucidate the FADS3 function.
自 2000 年被鉴定以来,尚未发现脂肪酸去饱和酶 3(Fads3)基因的功能。该基因位于 Fads 基因簇内,该基因簇还包含编码 Δ5-和 Δ6-去饱和酶的 Fads1 和 Fads2。基于这三个基因之间的序列同源性,Fads3 可能是一种新的脂肪酸去饱和酶。因此,了解其在多不饱和脂肪酸(PUFA)生物合成中的作用对于提高我们对脂质代谢的认识至关重要。基因表达研究提供了证据表明,与 Fads1 和 Fads2 相比,Fads3 在组织分布、选择性剪接和调节方面具有特异性。这些研究还确定了 Fads3 可能参与的可能的生理功能。因此,Fads3 基因在许多组织中转录,与其他器官(如肺或脾)相比,在肝脏中的表达较弱。Fads3 还被证明是 NK-κB、MYCN 或 p63 转录因子的靶基因,因此可能参与细胞存活机制。多态性分析强调了 Fads3 可能在脂质动态平衡中的作用,特别是通过调节胆固醇和甘油三酯的血浆水平。就蛋白质而言,FADS3 最近在啮齿动物中被描述。鉴定出的一种同工酶可能具有典型的脂肪酸去饱和酶结构,但尚未观察到酶活性。因此,必须考虑到催化和底物方面的去饱和酶多样性,以阐明 FADS3 的功能。