The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans
The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans
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细胞色素 b5 还原酶 HPO-19 是秀丽隐杆线虫多不饱和脂肪酸生物合成所必需的
DOI：
10.1016/j.bbalip.2016.01.009
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发表时间：
2016
影响因子：
4.8
通讯作者：
Liang Bin
中科院分区：
文献类型：
--
作者：
Zhang Yuru;Wang Haizhen;Zhang Jingjing;Hu Ying;Zhang Linqiang;Wu Xiaoyun;Su Xiong;Li Tingting;Zou Xiaoju;Liang Bin
多不饱和脂肪酸（Polyunsaturated fatty acids，PUFA）是主链含有一个以上双键的脂肪酸，其由一系列去饱和酶引入，所述去饱和酶在脂肪酸链中的特定碳原子处插入双键。已经确定，去饱和酶需要黄素蛋白-NADH依赖性细胞色素b5还原酶（简称为细胞色素b5还原酶）和细胞色素b5通过电子进行活化。然而，仍然不清楚这种多酶系统如何对不同的去饱和酶起作用。模式生物秀丽隐杆线虫含有7个PUFAS生物合成的去饱和酶（FAT-1、-2、-3、-4、-5、-6、-7），为表征不同的去饱和反应提供了极好的模型。在这里，我们表明，预测的细胞色素b5还原酶shpo-19和T05 H4.4的RNA干扰失活导致C18：1 n-9水平增加，但PUFA水平降低、小脂滴减少、脂肪积累减少、育雏数量减少和发育受损。膳食补充不同的脂肪酸表明，HPO-19和T05H4.4可能会影响FAT-1，FAT-2，FAT-3和FAT-4去饱和酶的活性，这表明这四种去饱和酶使用相同的细胞色素b5还原酶发挥作用。总的来说，这些发现表明，细胞色素b5还原酶HPO-19/T05H4.4是在C中生物合成PUFA的去饱和所必需的。优雅的
Polyunsaturated fatty acids (PUFAs) are fatty acids with backbones containing more than one double bond, which are introduced by a series of desaturases that insert double bonds at specific carbon atoms in the fatty acid chain. It has been established that desaturases need flavoprotein-NADH-dependent cytochrome b5 reductase (simplified as cytochrome b5 reductase) and cytochrome b5 to pass through electrons for activation. However, it has remained unclear how this multi-enzyme system works for distinct desaturases. The model organismCaenorhabditis eleganscontains seven desaturases (FAT-1, -2, -3, -4, -5, -6, -7) for the biosynthesis of PUFAS, providing an excellent model in which to characterize different desaturation reactions. Here, we show that RNAi inactivation of predicted cytochrome b5 reductaseshpo-19and T05H4.4 led to increased levels of C18:1n − 9 but decreased levels of PUFAs, small lipid droplets, decreased fat accumulation, reduced brood size and impaired development. Dietary supplementation with different fatty acids showed that HPO-19 and T05H4.4 likely affect the activity of FAT-1, FAT-2, FAT-3, and FAT-4 desaturases, suggesting that these four desaturases use the same cytochrome b5 reductase to function. Collectively, these findings indicate that cytochrome b5 reductase HPO-19/T05H4.4 is required for desaturation to biosynthesize PUFAs inC. elegans.