2D NMR-based metabolomics uncovers interactions between conserved biochemical pathways in the model organism Caenorhabditis elegans.
2D NMR-based metabolomics uncovers interactions between conserved biochemical pathways in the model organism Caenorhabditis elegans.
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DOI：
10.1021/cb3004644
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发表时间：
2013-02-15
影响因子：
4
通讯作者：
Schroeder, Frank C.
中科院分区：
文献类型：
--
作者：
Izrayelit, Yevgeniy;Robinette, Steven L.;Bose, Neelanjan;von Reuss, Stephan H.;Schroeder, Frank C.
Ascarosides是一种小分子信号，在C.线虫生物学，包括dauer形成，衰老和社会行为，但其生物合成的许多方面仍然未知。利用自动化的基于二维核磁共振的比较代谢组学，我们确定了在C. daf-22是一种与哺乳动物3-酮脂酰-CoA硫解酶具有同源性的基因，预计在保守的过氧化物酶体脂质β-氧化中起作用。两组乙醇酰胺的特征在于β-酮基官能化，证实了daf-22在蛔虫苷生物合成中的预测作用，而α-甲基取代则表明在C.优雅我们发现，响应于daf-22和其他过氧化物酶体基因缺陷的蛔虫苷乙醇酰胺形成与内源性大麻素库的严重消耗有关。这些结果表明过氧化物酶体脂质β-氧化和内源性大麻素的生物合成之间存在意想不到的相互作用，内源性大麻素是C.优雅我们的研究证明了无偏比较代谢组学在后生动物生化网络研究中的实用性。
Ascarosides are small-molecule signals that play a central role in C. elegans biology, including dauer formation, aging, and social behaviors, but many aspects of their biosynthesis remain unknown. Using automated 2D NMR-based comparative metabolomics, we identified ascaroside ethanolamides as shunt metabolites in C. elegans mutants of daf-22, a gene with homology to mammalian 3-ketoacyl-CoA thiolases predicted to function in conserved peroxisomal lipid β-oxidation. Two groups of ethanolamides feature β-keto functionalization confirming the predicted role of daf-22 in ascaroside biosynthesis, whereas α-methyl substitution points to unexpected inclusion of methylmalonte at a late stage in the biosynthesis of long-chain fatty acids in C. elegans. We show that ascaroside ethanolamide formation in response to defects in daf-22 and other peroxisomal genes is associated with severe depletion of endocannabinoid pools. These results indicate unexpected interaction between peroxisomal lipid β-oxidation and the biosynthesis of endocannabinoids, which are major regulators of lifespan in C. elegans. Our study demonstrates the utility of unbiased comparative metabolomics for investigating biochemical networks in metazoans.
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比较代谢组学揭示了丙烷剂的生物发生，这是秀丽隐杆线虫中小分子信号的模块化库。
影响因子：
15
作者：
von Reuss, Stephan H.;Bose, Neelanjan;Srinivasan, Jagan;Yim, Joshua J.;Judkins, Joshua C.;Sternberg, Paul W.;Schroeder, Frank C.
通讯作者：
Schroeder, Frank C.
影响因子：
4.3
作者：
Jones, Kevin T.;Ashrafi, Kaveh
通讯作者：
Ashrafi, Kaveh
DOI：
10.1016/0169-7439(93)85002-x
发表时间：
1993-03-01
影响因子：
3.9
作者：
DEJONG, S
通讯作者：
DEJONG, S
影响因子：
120.1
作者：
Nicholson, JK;Connelly, J;Holmes, E
通讯作者：
Holmes, E
DOI：
10.1073/pnas.0810338106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Butcher, Rebecca A.;Ragains, Justin R.;Mak, Ho Yi
通讯作者：
Mak, Ho Yi