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National Institute of Environmental Health Sciences

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Publication Detail

Title: Phosphatidylethanolamine N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline.

Authors: Zhu, Xiaonan; Song, Jiannan; Mar, Mei-Heng; Edwards, Lloyd J; Zeisel, Steven H

Published In Biochem J, (2003 Mar 15)

Abstract: 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.

PubMed ID: 12466019 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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