Article

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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    • "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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    • "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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