Molecular Distinction of Phosphatidylcholine Synthesis between the CDP-Choline Pathway and Phosphatidylethanolamine Methylation Pathway

Department of Biochemistry, Wake Forest University, Winston-Salem, North Carolina, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 11/1999; 274(42):29683-8. DOI: 10.1074/jbc.274.42.29683
Source: PubMed

ABSTRACT In addition to the CDP-choline pathway for phosphatidylcholine (PC) synthesis, 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 different and not interchangeable even though PC is the common product of both pathways. This study was designed to test the hypothesis that these two pathways produce different profiles of PC species. The PC species from these two pathways were labeled with specific stable isotope precursors, D9-choline and D4-ethanolamine, and analyzed by electrospray tandem mass spectrometry. 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, saturated (e.g. 16:0/18:0) species. On the other hand, PC molecules from the PE methylation pathway were much more diverse and were comprised of significantly more long chain, polyunsaturated (e.g. 18:0/20:4) species. PC species from the methylation pathway contained a higher percentage of arachidonate and were more diverse than those from the CDP-choline pathway. This profound distinction of PC profiles may contribute to the different functions of these two pathways in the liver.

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    • "In the liver, an alternative pathway utilizes PE to produce more PC and choline in a three-step methylation of PE by Sadenosylmethionine (SAM) catalysed by phosphatidylethanolamine-N-methyltransferase (PEMT). The PEMT pathway accounts for ∼30% of the hepatic PC synthesis and is coregulated with the CDP-choline Kennedy pathway [73] "
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    International Journal of Cell Biology 01/2014; 2014:709828. DOI:10.1155/2014/709828
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    • "Note that with the exception of 32:2, these components may correspond to two (32:1 and 34:2) or four (34:1) molecular species due to positional isomers. Pulse labeling of cells with stable isotope-labeled lipid precursors and subsequent analysis by ESI-MS/MS allows distinction between newly synthesized and pre-existing pools of most phospholipid classes, based on the difference in molecular mass conferred by the isotope labels [49] [50]. "
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    ABSTRACT: Phosphatidylcholine (PC) is a very abundant membrane lipid in most eukaryotes including the model organism Saccharomyces cerevisiae. Consequently, the molecular species profile of PC, i.e. the ensemble of PC molecules with acyl chains differing in number of carbon atoms and double bonds, is important in determining the physical properties of eukaryotic membranes, and should be tightly regulated. In this review current insights in the contributions of biosynthesis, turnover, and remodeling by acyl chain exchange to the maintenance of PC homeostasis at the level of the molecular species in yeast are summarized. In addition, the phospholipid class-specific changes in membrane acyl chain composition induced by PC depletion are discussed, which identify PC as key player in a novel regulatory mechanism balancing the proportions of bilayer and non-bilayer lipids in yeast.
    Biochimica et Biophysica Acta 04/2007; 1771(3):343-52. DOI:10.1016/j.bbalip.2006.07.010 · 4.66 Impact Factor
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    • "Hence, the reduced pool of PC that remains accessible to the cytoplasmic milieu may account for the partial turnover of PC observed in this study. Alternatively, studies using animal cells in culture (DeLong et al., 1999) and in yeast (Boumann et al., 2003) have found that PC that is synthesized by the methylation pathway versus that which is synthesized via the CDP–choline pathway can be distinguished by the length and saturation of their fatty acids. Hence, it could be argued that a minor PC pool that possesses a specific fatty acid modification may be recognized for rapid turnover during hypersaline stress. "
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    ABSTRACT: The role of phosphatidylcholine turnover during hypersaline stress is investigated in Saccharomyces cerevisiae. In the wild-type strain, 2180-1A hypersaline stress induced the rapid turnover of phosphatidylcholine, a major membrane lipid. Yeast cells were grown in the presence of [14C]-choline to label phosphatidylcholine. Upon shifting the cells to medium with 0.8 M NaCl, phosphatidylcholine levels were diminished by c. 30% within 20 min to yield glycerophosphocholine, a methylamine osmoprotectant that has been previously identified in renal cells. High-performance liquid chromatography studies showed that osmotically mediated glycerophosphocholine production was enhanced if 10 mM choline was added as a supplement to synthetic dextrose medium with 1.6 M NaCl, but glycine betaine was not detected. Enhanced glycerophosphocholine production also correlated with improved growth in media containing 1.6 M NaCl and choline. Enhanced growth is specific to methylamines: salt-stressed cells supplemented with 10 mM choline or glycine betaine showed enhanced growth relative to unsupplemented control cultures, but other additives had no effect on growth or adversely affected it. Nutritional effects are ruled out because yeast cannot use choline or glycine betaine as carbon or nitrogen sources in normal or high-salt medium. Finally, enhanced growth in hypersaline media with choline or glycine betaine is dependent on the choline permease Hnm1. These results in yeast highlight a similarity with mammalian renal cells, namely that phosphatidylcholine turnover contributes to osmotic adaptation via synthesis of the osmoprotectant glycerophosphocholine.
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