Monroig Oscar, Rotllant Josep, Cerdá-Reverter José M, Dick James R, Figueras Antonio, Tocher Douglas R
Institute of Aquaculture, University of Stirling, Stirling FK9 4LA, Scotland, UK.
Biochim Biophys Acta. 2010 Oct;1801(10):1145-54. doi: 10.1016/j.bbalip.2010.06.005. Epub 2010 Jul 1.
Elovl4 is a fatty acyl elongase that participates in the biosynthesis of very long-chain fatty acids (>/=C24), which are relatively abundant in skin (saturated chains), or retina, brain and testes (polyunsaturated chains) of mammals. In the present study we characterised two Elovl4 proteins, Elovl4a and Elovl4b, from zebrafish Danio rerio, and investigated their expression patterns during embryonic development. Heterologous expression in baker's yeast showed that both zebrafish Elovl4 proteins efficiently elongated saturated fatty acids up to C36, with 26:0 appearing the preferred substrate as reported for human ELOVL4. Interestingly, activity for the elongation of PUFA substrates was only shown by Elovl4b, which effectively converted eicosapentaenoic (20:5n-3) and arachidonic (20:4n-6) acids to elongated polyenoic products up to C36. Furthermore, zebrafish Elovl4b may be involved in the biosynthesis of docosahexaenoic acid (22:6n-3, DHA) as it had the capacity to elongate 22:5n-3 to 24:5n-3 which can be subsequently desaturated and chain shortened to DHA in peroxisomes. The distinct functional roles of zebrafish Elovl4 proteins were also reflected in their spatial-temporal expression patterns during ontogeny. Analyses by whole-mount in situ hybridisation in zebrafish embryos showed that elovl4a was expressed in neuronal tissues (wide-spread distribution in the head area), with elovl4b specifically expressed in epiphysis (pineal gland) and photoreceptor cells in the retina. Similarly, tissue distribution in adults revealed that elovl4a transcripts were found in most tissues analysed, whereas elovl4b expression was essentially restricted to eye and gonads. Overall, the results suggest that zebrafish elovl4b resembles other mammalian orthologues in terms of function and expression patterns, whereas elovl4a may represent an alternative elongase not previously described in vertebrates.
Elovl4是一种脂肪酰基延长酶，参与超长链脂肪酸（≥C24）的生物合成，这种脂肪酸在哺乳动物的皮肤（饱和链）、视网膜、大脑和睾丸（多不饱和链）中相对丰富。在本研究中，我们从斑马鱼（Danio rerio）中鉴定出两种Elovl4蛋白，即Elovl4a和Elovl4b，并研究了它们在胚胎发育过程中的表达模式。在面包酵母中的异源表达表明，两种斑马鱼Elovl4蛋白都能有效地将饱和脂肪酸延长至C36，如人ELOVL4所报道的那样，26:0似乎是首选底物。有趣的是，只有Elovl4b表现出对多不饱和脂肪酸底物的延长活性，它能有效地将二十碳五烯酸（20:5n-3）和花生四烯酸（20:4n-6）转化为长达C36的延长多烯产物。此外，斑马鱼Elovl4b可能参与二十二碳六烯酸（22:6n-3，DHA）的生物合成，因为它有能力将22:5n-3延长至24:5n-3，随后可在过氧化物酶体中去饱和并缩短链长形成DHA。斑马鱼Elovl4蛋白不同的功能作用也反映在它们个体发育过程中的时空表达模式上。对斑马鱼胚胎进行的整体原位杂交分析表明，elovl4a在神经组织中表达（在头部区域广泛分布），而elovl4b则特异性地表达于松果体（松果腺）和视网膜中的光感受器细胞。同样，成体组织分布显示，在所分析的大多数组织中都发现了elovl4a转录本，而elovl4b的表达基本上局限于眼睛和性腺。总体而言，结果表明斑马鱼elovl4b在功能和表达模式方面与其他哺乳动物的直系同源物相似，而elovl4a可能代表一种脊椎动物中先前未描述的替代延长酶。
