Choline is an essential nutrient for humans and is derived from the diet as well as from de novo synthesis involving methylation of phosphatidylethanolamine catalysed by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT). This is the only known pathway that produces new choline molecules. We used mice with a disrupted Pemt-2 gene (which encodes PEMT; Pemt-/-) that have previously been shown to possess no hepatic PEMT enzyme. Male, female and pregnant Pemt-/- and wild-type mice (n = 5—6 per diet group) were fed diets of different choline content (deficient, control, and supplemented). Livers were collected and analysed for choline metabolites, steatosis, and apoptotic [terminal deoxynucleotidyl transferase-mediated dUTP—biotin nick end-labelling (TUNEL)] positive cells. We found that, in livers of Pemt-/- mice fed any of the diets, there was hepatic steatosis and significantly higher occurrence of TUNEL positive cells compared with wild-type controls. In male, female and pregnant mice, liver phosphatidylcholine concentrations were significantly decreased in Pemt-/- choline deficient and in Pemt-/- choline control groups but returned to normal in Pemt-/- choline supplemented groups. Phosphocholine concentrations in liver were significantly diminished in knockout mice even when choline was supplemented to above dietary requirements. These results show that PEMT normally supplies a significant portion of the daily choline requirement in the mouse and, when this pathway is knocked out, mice are unable to attain normal concentrations of all choline metabolites even with a supplemental source of dietary choline.
Phosphatidylethanolamine N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline
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Xiaonan ZHU, Jiannan SONG, Mei-Heng MAR, Lloyd J. EDWARDS, Steven H. ZEISEL; Phosphatidylethanolamine N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline. Biochem J 15 March 2003; 370 (3): 987–993. doi: https://doi.org/10.1042/bj20021523
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