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

Abstract

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 2/2 ) 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 taurocholatecontaining 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 2/2 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 2/2 and control mice. Mdr2 mRNA and protein abundance did not differ between Pemt 2/2 and wild-type mice. The cytidylyltransferase activity in hepatic lysates was increased by 20% in Pemt 2/2 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.-Verkade, H.

Dietary sucrose is essential to the development of liver injury in the methionine-choline-deficient model of steatohepatitis

“…Indeed, it is remarkable that hepatic phospholipids in MCD mice remain at near-normal levels despite a complete cutoff of exogenous precursors. This implies the existence of strong homeostatic mechanisms to preserve cellular phospholipids under conditions of stress, which could be achieved by regulation of VLDL secretion, biliary phospholipid secretion, or both ( 48,49 ). Ip et al ( 50 ) made a similar observation previously.…”

CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis

“…Both the CDP-choline and PE-methylation pathways contribute PC to bile secretion, and knockout of either Pcyt1a or Pemt has no effect on bile secretion or composition, suggesting effective metabolic compensation [104,107]. When PC synthesis was compromised in the liver of PEMT-null mice, liver failure caused by a choline-depleted diet was prevented by knockout of the PC-specific flippase MDR2 [108].…”

“…Lipid droplets (LD) [107] are storage depots for the neutral lipids triacylglycerol and sterol ester that are surrounded by a phospholipid monolayer composed of mainly PC (70%) and PE (20%), with traces of PI and PS [126,127]. LDs form via budding from the ER and accumulate in the cytosol [128].…”

The mechanism of increased biliary lipid secretion in mice with genetic inactivation of bile salt export pump

“…T␤MCA infusion rates were 150, 300, and 450 nmol/min, each for 30 min, followed by 600 nmol/min for 60 min. Infusion rates and concentrations of T␤MCA were similar to previously reported infusion experiments with tauroursodexoycholic acid (Pemt Ϫ/Ϫ mice) (44) and similar to others with other BS described in literature (13,31,35). Body temperature was stabilized during bile collection using a humidified incubator.…”