The unique acyl chain specificity of biliary phosphatidylcholines in mice is independent of their biosynthetic origin in the liver

Abstract

The liver synthesizes phosphatidylcholine (PC) de novo from choline via the CDP-choline pathway, and from phosphatidylethanolamine (PE) via the phosphatidylethanolamine N-methyltransferase (PEMT) pathway. Significant amounts of PC, which are highly specific in their acyl chain composition, are secreted into bile by the liver. To determine whether either of the 2 PC biosynthetic routes is sufficient to provide physiological PC concentrations in bile, or is responsible for the unique acyl chain composition of bile PC, we analyzed gallbladder bile composition in mice that synthesized PC either via the PEMT pathway (induced by feeding a choline-deficient diet) or the CDPcholine pathway (based on genetic PEMT-deficiency). The PC concentration in gallbladder bile of mice that synthesize PC mainly via the CDP-choline pathway was comparable with control mice that synthesize PC via both pathways, whereas it was reduced by Ϸ40% in mice that synthesize PC via the PEMT pathway. The acyl chain composition of bile PC was similar irrespective of the active PC biosynthetic pathway in the liver. These data demonstrate that the CDP-choline pathway alone, but not the PEMT pathway alone, can account for physiological concentrations of PC in gallbladder bile. Moreover, the specificity of biliary PC fatty acyl composition is determined independently from the synthetic origin of PC. (HEPATOLOGY 1999;30:725-729.)

Insights into the requirement of phosphatidylcholine synthesis for liver function in mice

“…Because the specific activity of PEMT-derived PC in the bile was approximately the same as in the liver, it appears that PEMT-derived PC is not specifically targeted for bile secretion. These results are consistent with those of a previous study aimed at determining which of the two PC biosynthetic pathways was responsible for contributing PC for bile secretion (35). The results indicated that, although mice depend more on the CDP-choline than on the PEMT pathway for secretion of PC into bile, the fatty acid composition of the secreted PC was similar irrespective of the source of PC.…”

Localization of the PE methylation pathway and SR-BI to the canalicular membrane

“…Under normal metabolic conditions, it is thought that the CDP-choline pathway accounts for 60-80% of liver PC biosynthesis (18). The CDP-choline and the PE methylation pathways can both provide PC for lipoprotein and membrane biosynthesis and bile secretion (19). In the current study, we show that BHMT and PEMT also localize to basolateral and canalicular membranes, suggesting they may serve to convert PE, known to be present in relatively high concentrations in the inner leaflet of plasma membranes, to PC for specific needs (20,21).…”

Phosphorylation of Saccharomyces cerevisiae Choline Kinase on Ser30 and Ser85 by Protein Kinase A Regulates Phosphatidylcholine Synthesis by the CDP-choline Pathway

“…It serves as a major structural component of cellular membranes (1)(2)(3)(4), pulmonary surfactant (5), serum lipoproteins (6), and bile (7). There is strong interest in understanding the regulation of PC metabolism, because this phospholipid serves as a reservoir for several lipid messengers (e.g.…”