Phosphatidylcholine homeostasis and liver failure

Zhaoyu Li, Luis B. Agellon, Dennis E. Vance

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

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 A2, 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.

Original languageEnglish (US)
Pages (from-to)37798-37802
Number of pages5
JournalJournal of Biological Chemistry
Volume280
Issue number45
DOIs
StatePublished - Nov 11 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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