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The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans.

Biochim. Biophys. Acta. 2016 Apr;1861(4):310-9. Epub 2016 Jan 20
Yuru Zhang 1 , Haizhen Wang 2 , Jingjing Zhang 2 , Ying Hu 3 , Linqiang Zhang 2 , Xiaoyun Wu 4 , Xiong Su 5 , Tingting Li 5 , Xiaoju Zou 6 , Bin Liang 7
Yuru Zhang 1 , Haizhen Wang 2 , Jingjing Zhang 2 , Ying Hu 3 , Linqiang Zhang 2 , Xiaoyun Wu 4 , Xiong Su 5 , Tingting Li 5 , Xiaoju Zou 6 , Bin Liang 7
+ et al

[No authors listed]

Author information
  • 1 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; College of Fisheries, Henan Normal University, Xinxiang, Henan 453007, China.
  • 2 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
  • 3 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
  • 4 Key Laboratory of Puer Tea Science, Ministry of Education (Yunnan Agricultural University), Kunming 650201, China.
  • 5 Department of Biochemistry and Molecular Biology, Soochow University Medical College, Suzhou 215006, China.
  • 6 Department of Life Science and Biotechnology, Key Laboratory of Special Biological Resource Development and Utilization of University in Yunnan Province, Kunming University, Kunming 650214, China. Electronic address: xiaojuzou@163.com.
  • 7 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Electronic address: liangb@mail.kiz.ac.cn.

摘要


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 organism Caenorhabditis elegans contains 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 inactivation of predicted cytochrome b5 reductases hpo-19 and 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 in C. elegans.

KEYWORDS: C. elegans, Cytochrome b5 reductase HPO-19 and T05H4.4, Fatty acid desaturation, Polyunsaturated fatty acids (PUFAs)