Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway

In addition to the CDP-choline pathway for phosphatidylcholine (PC) synthes is, the liver has a unique phosphatidylethanolamine (PE) methyltransferase activity for PC synthesis via three methylations of the ethanolamine moiety of PE, Previous studies indicate that the two pathways are functionally di fferent and not interchangeable even though PC is the common product of bot h pathways. This study was designed to test the hypothesis that these two p athways produce different profiles of PC species. The PC species from these two pathways were labeled with specific stable isotope precursors, DS-chol ine and D4-ethanolamine, and analyzed by electrospray tandem mass spectrome try. Our studies revealed a profound distinction in PC profiles between the CDP-choline pathway and the PE methylation pathway, PC molecules produced from the CDP-choline pathway were mainly comprised of medium chain, saturat ed (e.g. 16:0/18:0) species. On the other hand, PC molecules from the PE me thylation pathway were much more diverse and were comprised of significantl y more long chain, polyunsaturated (e.g. 18:0/20:4) species. PC species fro m the methylation pathway contained a higher percentage of arachidonate and were more diverse than those from the CDP-choline pathway, This profound d istinction of PC profiles may contribute to the different functions of thes e two pathways in the liver.