Gregory Melissa K, James Michael J
Biochim Biophys Acta. 2014 Dec;1841(12):1656-60. doi: 10.1016/j.bbalip.2014.10.001.
The synthesis of the omega-3 long-chain polyunsaturated fatty acids (LCPUFA) eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n--3) from dietary α-linolenic acid (ALA; 18:3n--3) requires three desaturation and three elongation steps in vertebrates. The elongation of EPA to docosapentaenoic acid (DPA; 22:5n-3) can be catalysed by the elongase enzymes Elov15 or Elov12, but further elongation of DPA to 24:5n-3, the penultimate precursor of DHA, is limited to Elov12, at least in mammals. Elov15 enzymes have been characterised from seventeen fish species but Elov12 enzymes have only been characterised in two of these fish. The essentiality of Elov12 for DHA synthesis is unknown in fish. This study is the first to identify an Elov12 in rainbow trout (Oncorhynchus mykiss) and functionally chafacterise the Elovl5 and Elovl2 using a yeast expression system. Elovl5 was active with C18-20 PUFA substrates and not C22 PUFA. In contrast, Elovl2 was active with C20-22 PUFA substrates and not C18 PUFA. Thus, rainbow trout is dependent on Elovl2 for DPA to 24:5n--3 synthesis and ultimately DHA synthesis. The expression of elov15 was significantly higher than elov12 in liver. Elucidating this dependence on Elov12 to elongate DPA and the low elov12 gene expression compared with elovl5 are critical findings in understanding the potential for rainbow trout to synthesize DHA.
在脊椎动物中,从膳食中的α-亚麻酸(ALA;18:3n-3)合成ω-3长链多不饱和脂肪酸(LCPUFA)二十碳五烯酸(EPA;20:5n-3)和二十二碳六烯酸(DHA;22:6n-3)需要三步去饱和和三步延长反应。EPA延长至二十二碳五烯酸(DPA;22:5n-3)可由延长酶Elov15或Elov12催化,但DPA进一步延长至DHA的倒数第二个前体24:5n-3,至少在哺乳动物中仅限于由Elov12催化。已对17种鱼类的Elov15酶进行了表征,但仅对其中两种鱼类的Elov12酶进行了表征。在鱼类中,Elov12对DHA合成的必要性尚不清楚。本研究首次在虹鳟(Oncorhynchus mykiss)中鉴定出Elov12,并使用酵母表达系统对Elov15和Elov12进行了功能表征。Elov15对C18-20多不饱和脂肪酸底物有活性,而对C22多不饱和脂肪酸无活性。相反,Elov12对C20-22多不饱和脂肪酸底物有活性,而对C18多不饱和脂肪酸无活性。因此,虹鳟依赖Elov12将DPA合成24:5n-3,最终合成DHA。肝脏中elov15的表达明显高于elov12。阐明这种对Elov12延长DPA的依赖性以及与elov15相比elov12基因表达较低,是理解虹鳟合成DHA潜力的关键发现。