J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M700278-JLR200 on June 26, 2007

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Journal of Lipid Research, Vol. 48, 2058-2064, September 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

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

Henkjan J. Verkade1,*, Rick Havinga*, David J. Shields2,{dagger}, Henk Wolters*, Vincent W. Bloks*, Folkert Kuipers*, Dennis E. Vance{dagger} and Luis B. Agellon{dagger}

* Pediatric Gastroenterology/Research Laboratory Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
{dagger} Canadian Institutes of Health Research Group on Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada

Published, JLR Papers in Press, June 26, 2007.

2 Present address of D. J. Shields: Moores UCSD Cancer Center, 3855 Health Sciences Drive, #0803, La Jolla, CA 92093-0803.

1 To whom correspondence should be addressed. e-mail: 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 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 multi-drug-resistant protein 2 (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/100 g body weight, respectively). During acute or chronic bile salt administration, the biliary PC secretion rates increased similarly 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 the biosynthesis of PC via the PEMT pathway is not quantitatively essential for biliary PC secretion under acute or chronic bile salt administration.

Supplementary key words biliary lipids • bile salts • phosphatidylcholine biosynthesis • liver • cholesterol


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Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.