Expression of phosphatidylethanolamine N-methyltransferase-2 is markedly enhanced in long term choline-deficient rats.
When rats are fed a choline-deficient (CD) diet, acute fatty liver develops along with other biochemical changes. However, when choline deficiency is prolonged, the growth rate of CD rats is similar to that of control rats fed a choline-supplemented diet. Furthermore, CD rats maintain their levels of choline-containing lipids, such as phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin. The mechanism for this compensation in CD rats was investigated. We screened the major tissues for the activities of two important enzymes involved in the biosynthesis of phosphatidylcholine, CTP:phosphocholine cytidylyltransferase (CT) and phosphatidylethanolamine N-methyltransferase (PEMT). Only the livers of CD rats had higher specific enzyme activities of PEMT and CT than control animals. The amount of PEMT2, one of two PEMTs in liver, increased 5-fold in CD rats after 6 weeks on the CD diet. A similar increase in the level of PEMT2 mRNA suggested that this activation was due to enhanced expression of the PEMT2 gene in CD livers. The labeling of phosphatidylcholine in isolated hepatocytes from CD rats was consistent with the conversion of PE to PC being increased as a result of a higher expression of liver PEMT. We conclude that activation of PE methylation at the level of gene expression may be the mechanism by which CD rats compensate for the lack of dietary choline.
Cui
Z
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Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.
Vance
D E
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D000818:Animals; D002796:Choline Deficiency / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D019916:Choline-Phosphate Cytidylyltransferase; D004789:Enzyme Activation; D008099:Liver / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain
D010743:Phospholipids; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase