First Author | Li Z | Year | 2005 |
Journal | J Biol Chem | Volume | 280 |
Issue | 45 | Pages | 37798-802 |
PubMed ID | 16144842 | Mgi Jnum | J:102893 |
Mgi Id | MGI:3608206 | Doi | 10.1074/jbc.M508575200 |
Citation | Li Z, et al. (2005) Phosphatidylcholine homeostasis and liver failure. J Biol Chem 280(45):37798-802 |
abstractText | In mammals, the only endogenous pathway for choline biosynthesis is the methylation of phosphatidylethanolamine to phosphatidylcholine (PC) by phosphatidylethanolamine N-methyltransferase (PEMT) coupled to PC degradation. Complete choline deprivation in mice by feeding Pemt(-/-) mice a choline-deficient (CD) diet decreases hepatic PC by 50% and is lethal within 5 days. PC secretion into bile is mediated by a PC-specific flippase, multiple drug-resistant protein 2 (MDR2). Here, we report that mice that lack both PEMT and MDR2 and are fed a CD diet survive for >90 days. Unexpectedly, the amount of PC also decreases by 50% in the livers of Mdr2(-/-)/Pemt(-/-) mice. The Mdr2(-/-)/Pemt(-/-) mice adapt to the severe choline deprivation via choline recycling by induction of phospholipase A(2), choline kinase, and CTP:phosphocholine cytidylyltransferase activities and by a strikingly decreased expression of choline oxidase. The ability of Mdr2(-/-)/Pemt(-/-) mice to survive complete choline deprivation suggests that acute lethality in CD-Pemt(-/-) mice results from rapid depletion of hepatic PC via biliary secretion. |