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, Canada T6G 2S2.
Biochim Biophys Acta. 2007 Jul;1771(7):893-900. doi: 10.1016/j.bbalip.2007.04.009. Epub 2007 Apr 21.
Choline is (95%) found largely in the biosphere as a component of phosphatidylcholine (PC) which is made from choline via the CDP-choline pathway. Animals obtain choline from both the diet and via endogenous biosynthesis that involves the conversion of phosphatidylethanolamine into PC by phosphatidylethanolamine N-methyltransferase (PEMT), followed by PC catabolism. We have uncovered a striking gender-specific conservation of choline in female mice that does not occur in male mice. Female Pemt(-/-) mice maintained hepatic PC/total choline levels during the first day of choline deprivation and escaped liver damage whereas male Pemt(-/-) mice did not. Plasma PC levels in high-density lipoproteins (HDLs) were higher in male Pemt(-/-) mice than those in females before choline deprivation. Interestingly, after choline deprivation for 1 day, female, but not male, Pemt(-/-) mice increased HDL-PC levels. Glybenclamide, an inhibitor of PC efflux mediated by ABC transporters, eliminated this response to choline deprivation in females. These data suggest that (i) increased PC efflux from extra-hepatic tissues to HDLs in the circulation provided sufficient choline for the liver and compensated for loss of hepatic PC during the initial stages of choline deprivation in female, but not male, Pemt(-/-) mice, and (ii) plasma HDL in female mice has an important function in maintenance of hepatic PC as an acute response to severe choline deprivation.
胆碱（95%）在生物圈中主要以磷脂酰胆碱（PC）的成分形式存在，PC是通过CDP-胆碱途径由胆碱合成的。动物可从饮食中获取胆碱，也可通过内源性生物合成获得，内源性生物合成过程包括磷脂酰乙醇胺N-甲基转移酶（PEMT）将磷脂酰乙醇胺转化为PC，随后进行PC分解代谢。我们发现雌性小鼠中胆碱存在显著的性别特异性保守现象，而雄性小鼠中不存在。雌性Pemt(-/-)小鼠在胆碱缺乏的第一天维持肝脏PC/总胆碱水平，并避免了肝脏损伤，而雄性Pemt(-/-)小鼠则没有。在胆碱缺乏前，雄性Pemt(-/-)小鼠高密度脂蛋白（HDL）中的血浆PC水平高于雌性。有趣的是，在胆碱缺乏1天后，雌性而非雄性Pemt(-/-)小鼠的HDL-PC水平升高。格列本脲是一种ABC转运蛋白介导的PC外排抑制剂，它消除了雌性小鼠对胆碱缺乏的这种反应。这些数据表明：（i）在雌性而非雄性Pemt(-/-)小鼠中，从肝外组织到循环中HDL的PC外排增加，为肝脏提供了足够的胆碱，并补偿了胆碱缺乏初始阶段肝脏PC的损失；（ii）雌性小鼠的血浆HDL在作为对严重胆碱缺乏的急性反应维持肝脏PC方面具有重要功能。
