Li Zhaoyu, Agellon Luis B, Vance Dennis E
Department of Biochemistry and Canadian Institutes of Health Research Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
J Biol Chem. 2007 Apr 6;282(14):10283-9. doi: 10.1074/jbc.M611726200. Epub 2007 Feb 5.
Choline is an important nutrient for mammals. Choline can also be generated by the catabolism of phosphatidylcholine synthesized in the liver by the methylation of phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase (PEMT). Complete choline deprivation is achieved by feeding Pemt(-)(/)(-) mice a choline-deficient diet and is lethal due to liver failure. Mice that lack both PEMT and MDR2 (multiple drug-resistant protein 2) successfully adapt to choline deprivation via hepatic choline recycling. We now report another mechanism involved in this adaptation, choline redistribution. Normal levels of choline-containing metabolites were maintained in the brains of choline-deficient Mdr2(-)(/)(-)/Pemt(-)(/)(-) mice for 90 days despite continued choline consumption via oxidation. Choline oxidase activity had not been previously detected in the brain. Plasma levels of choline were also maintained for 90 days, whereas plasma phosphatidylcholine levels decreased by >60%. The injection of [(3)H]choline into Mdr2(-)(/)(-)/Pemt(-)(/)(-) mice revealed a redistribution of choline among tissues. Although CD-Pemt(-)(/)(-) mice failed to adapt to choline deprivation, choline redistribution was also initiated in these mice. The data suggest that adaptation to choline deprivation is not restricted to liver via choline recycling but also occurs in the whole animal via choline redistribution.
胆碱是哺乳动物的一种重要营养素。胆碱也可由肝脏中通过磷脂酰乙醇胺N-甲基转移酶（PEMT）将磷脂酰乙醇胺甲基化合成的磷脂酰胆碱分解代谢产生。通过给Pemt(-)(/)(-)小鼠喂食缺乏胆碱的饮食可实现完全胆碱剥夺，且由于肝功能衰竭而致死。同时缺乏PEMT和多药耐药蛋白2（MDR2）的小鼠可通过肝脏胆碱循环成功适应胆碱剥夺。我们现在报告了这种适应过程中涉及的另一种机制，即胆碱重新分布。尽管通过氧化持续消耗胆碱，但胆碱缺乏的Mdr2(-)(/)(-)/Pemt(-)(/)(-)小鼠大脑中含胆碱代谢物的水平在90天内保持正常。此前在大脑中未检测到胆碱氧化酶活性。血浆胆碱水平也维持了90天，而血浆磷脂酰胆碱水平下降了>60%。向Mdr2(-)(/)(-)/Pemt(-)(/)(-)小鼠注射[(3)H]胆碱显示胆碱在组织间重新分布。尽管CD-Pemt(-)(/)(-)小鼠未能适应胆碱剥夺，但这些小鼠也启动了胆碱重新分布。数据表明，对胆碱剥夺的适应不仅通过胆碱循环局限于肝脏，还通过胆碱重新分布在整个动物体内发生。
