Phosphatidylcholine homeostasis and liver failure

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

Research output: Contribution to journalArticle

91 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Liver Failure
Choline
Phosphatidylcholines
Liver
Homeostasis
Phosphatidylethanolamine N-Methyltransferase
choline oxidase
Nutrition
Choline-Phosphate Cytidylyltransferase
Choline Kinase
Diet
Methylation
Mammals
Phospholipases A2
Biosynthesis
Recycling
Bile
Pharmaceutical Preparations
Proteins
Degradation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphatidylcholine homeostasis and liver failure. / Li, Zhaoyu; Agellon, Luis B.; Vance, Dennis E.

In: Journal of Biological Chemistry, Vol. 280, No. 45, 11.11.2005, p. 37798-37802.

Research output: Contribution to journalArticle

Li, Zhaoyu ; Agellon, Luis B. ; Vance, Dennis E. / Phosphatidylcholine homeostasis and liver failure. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 45. pp. 37798-37802.
@article{4adc82a5cb4f475b942d2ec74531bbe4,
title = "Phosphatidylcholine homeostasis and liver failure",
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.",
author = "Zhaoyu Li and Agellon, {Luis B.} and Vance, {Dennis E.}",
year = "2005",
month = "11",
day = "11",
doi = "10.1074/jbc.M508575200",
language = "English (US)",
volume = "280",
pages = "37798--37802",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "45",

}

TY - JOUR

T1 - Phosphatidylcholine homeostasis and liver failure

AU - Li, Zhaoyu

AU - Agellon, Luis B.

AU - Vance, Dennis E.

PY - 2005/11/11

Y1 - 2005/11/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=27844577744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27844577744&partnerID=8YFLogxK

U2 - 10.1074/jbc.M508575200

DO - 10.1074/jbc.M508575200

M3 - Article

C2 - 16144842

AN - SCOPUS:27844577744

VL - 280

SP - 37798

EP - 37802

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 45

ER -