J. Lipid Res.
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A more recent version of this article appeared on September 1, 2007

Papers In Press, published online ahead of print June 26, 2007
J. Lipid Res., doi:10.1194/jlr.M700278-JLR200
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Submitted on June 14, 2007
Accepted on June 25, 2007

The phosphatidylethanolamine N-methyltransferase pathway is quantitatively not essential for biliary phosphatidylcholine secretion

Henkjan J. Verkade, Rick Havinga, David J. Shields, Henk Wolters, Vincent W. Bloks, Folkert Kuipers, Dennis E. Vance, and Lou B. Agellon

Pediatric Gastroenterology, Dept. Pediatrics, University Medical Center Groningen, University of Groningen, Groningen 9736 RE

Corresponding Author: h.j.verkade{at}med.umcg.nl

The phosphatidylethanolamine N-methyltransferase (PEMT) pathway of phosphatidylcholine (PC) biosynthesis is not essential for the highly specific acyl chain composition of biliary PC. We presently evaluated whether the PEMT pathway is quantitatively important for biliary PC secretion in mice under various experimental conditions. Biliary bile salt and PC secretion were determined in mice in which the gene encoding PEMT was inactivated (Pemt-/-) and in wild type mice, under basal conditions, during acute metabolic stress (intravenous infusion of the bile salt tauroursodeoxycholate) and during chronic metabolic stress (feeding a taurocholate-containing diet for 1 week). The activity of CTP:phosphocholine cytidylyltransferase, the rate-limiting enzyme of PC biosynthesis via the CDP-choline pathway, and the abundance of Mdr2 (encoded by the AbcB4 gene), the canalicular membrane flippase essential for biliary PC secretion, were determined. Under basal conditions, Pemt-/- and wild type mice exhibited similar biliary secretion rates of bile salt and PC (~145 and ~28 nmol/min.100g body weight, respectively). During acute or chronic bile salt administration, the biliary PC secretion rates similarly increased in Pemt-/- and control mice. Mdr2 mRNA and protein abundance did not differ between Pemt-/- and wild type mice. The cytidylyltransferase activity in hepatic lysates was increased by 20% in Pemt-/- mice fed the basal (bile salt-free) diet (p<0.05). We conclude that biosynthesis of PC via the PEMT pathway is not quantitatively essential for biliary PC secretion under acute or chronic bile salt administration.


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