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.
Skip Nav Destination
Article navigation
March 2003
- PDF Icon PDF LinkFront Matter
Research Article|
March 15 2003
Phosphatidylethanolamine N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline
Xiaonan ZHU;
Xiaonan ZHU
∗Department of Nutrition, CB #7461, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7400, U.S.A.,
Search for other works by this author on:
Jiannan SONG;
Jiannan SONG
∗Department of Nutrition, CB #7461, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7400, U.S.A.,
Search for other works by this author on:
Mei-Heng MAR;
Mei-Heng MAR
∗Department of Nutrition, CB #7461, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7400, U.S.A.,
Search for other works by this author on:
Lloyd J. EDWARDS;
Lloyd J. EDWARDS
†Department of Biostatistics, CB #7420, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, U.S.A.
Search for other works by this author on:
Steven H. ZEISEL
Steven H. ZEISEL
1
∗Department of Nutrition, CB #7461, School of Public Health, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7400, U.S.A.,
1To whom correspondence should be addressed (e-mail steven_zeisel@unc.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 30 2002
Revision Received:
November 20 2002
Accepted:
December 05 2002
Accepted Manuscript online:
March 15 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 370 (3): 987–993.
Article history
Received:
September 30 2002
Revision Received:
November 20 2002
Accepted:
December 05 2002
Accepted Manuscript online:
March 15 2003
Citation
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
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.