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Gene Review

Pemt  -  phosphatidylethanolamine N-methyltransferase

Mus musculus

Synonyms: PEAMT, PEMT, PEMT2, Pempt, Pempt2, ...
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Disease relevance of Pemt


High impact information on Pemt


Biological context of Pemt

  • The concentrations of S-adenosylmethionine (up 21%; p<0.05) and methylation of DNA (up 46%) and proteins (up 12%; p<0.01) in hippocampus were significantly increased in Pemt-/- mice, suggesting that increased S-adenosylmethionine availability may mediate the observed developmental changes [8].
  • We previously reported that choline availability during pregnancy alters mitosis and neuronal protein expression during fetal brain development in wild-type mice and rats, and that Pemt-/- mice become choline deficient [8].
  • Pregnant Pemt-/- and wild-type mice were fed AIN-76A diet until gestation day 17 (E17) when the fetal brains were harvested [8].
  • We have hypothesized that phosphatidylethanolamine-N-methyl transferase (PEMT) up-regulation is a consequence of MCD diet administration, and is important for the pathogenesis of steatohepatitis in this model [9].
  • The present study used quantitative lipid metabolite profiling to characterize lipid metabolism in PEMT-deficient mice fed diets containing varying concentrations of choline [3].

Anatomical context of Pemt


Associations of Pemt with chemical compounds

  • Moreover, female and, to a lesser extent, male Pemt-/- mice showed a striking 40% decrease in plasma PC and cholesterol in high density lipoproteins [11].
  • Lipid analyses of plasma and liver indicated that male Pemt-/- mice accumulated triacylglycerols in their livers and were unable to secrete the same amount of triacylglycerols from the liver as did Pemt+/+ mice [11].
  • Experiments in which mice were injected with Triton WR1339 showed that, whereas hepatic apoB100 secretion was decreased in male Pemt-/- mice, the decrease in plasma apoB48 in male Pemt-/- mice was not due to reduced secretion [11].
  • Plasma levels of triacylglycerol and both apolipoproteins B100 and B48 were significantly decreased only in male Pemt-/- mice [11].
  • Since phosphatidyldimethylethanolamine (PDME) has physical properties similar to those of phosphatidylcholine (PC), we hypothesized that dimethylethanolamine (DME) would be converted into PDME that might substitute for PC, and therefore abrogate the liver damage in the Pemt -/- mice fed a CD diet [1].
  • Hepatocytes isolated from Pemt(-/-) mice released cholesterol and PC into the medium as efficiently as did hepatocytes from Pemt(+/+) mice [12].

Enzymatic interactions of Pemt


Regulatory relationships of Pemt

  • However, the effect of decreased phosphatidylcholine secretion and modulation of PEMT on the development of diet-induced steatohepatitis in Mdr2 (+/-) mice has not been explored [9].

Other interactions of Pemt


Analytical, diagnostic and therapeutic context of Pemt

  • 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 [16].
  • 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 [16].
  • Immunoblotting confirmed the presence of BHMT on the canalicular membrane, failed to reveal the presence of the second enzyme in this pathway, methionine adenosyltransferase, and localized the third enzyme of the pathway, PE N-methyltransferase (PEMT) [17].


  1. Dimethylethanolamine does not prevent liver failure in phosphatidylethanolamine N-methyltransferase-deficient mice fed a choline-deficient diet. Waite, K.A., Vance, D.E. Biochim. Biophys. Acta (2004) [Pubmed]
  2. An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins. Noga, A.A., Zhao, Y., Vance, D.E. J. Biol. Chem. (2002) [Pubmed]
  3. Phosphatidylethanolamine-N-methyltransferase activity and dietary choline regulate liver-plasma lipid flux and essential fatty acid metabolism in mice. Watkins, S.M., Zhu, X., Zeisel, S.H. J. Nutr. (2003) [Pubmed]
  4. Disruption of the murine gene encoding phosphatidylethanolamine N-methyltransferase. Walkey, C.J., Donohue, L.R., Bronson, R., Agellon, L.B., Vance, D.E. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. The unique acyl chain specificity of biliary phosphatidylcholines in mice is independent of their biosynthetic origin in the liver. Agellon, L.B., Walkey, C.J., Vance, D.E., Kuipers, F., Verkade, H.J. Hepatology (1999) [Pubmed]
  6. Physiological regulation of phospholipid methylation alters plasma homocysteine in mice. Jacobs, R.L., Stead, L.M., Devlin, C., Tabas, I., Brosnan, M.E., Brosnan, J.T., Vance, D.E. J. Biol. Chem. (2005) [Pubmed]
  7. Stearoyl-CoA desaturase 1 deficiency increases CTP:choline cytidylyltransferase translocation into the membrane and enhances phosphatidylcholine synthesis in liver. Dobrzyn, A., Dobrzyn, P., Miyazaki, M., Sampath, H., Chu, K., Ntambi, J.M. J. Biol. Chem. (2005) [Pubmed]
  8. Deletion of the Pemt gene increases progenitor cell mitosis, DNA and protein methylation and decreases calretinin expression in embryonic day 17 mouse hippocampus. Zhu, X., Mar, M.H., Song, J., Zeisel, S.H. Brain Res. Dev. Brain Res. (2004) [Pubmed]
  9. Mice heterozygous for the Mdr2 gene demonstrate decreased PEMT activity and diminished steatohepatitis on the MCD diet. Igolnikov, A.C., Green, R.M. J. Hepatol. (2006) [Pubmed]
  10. Involvement of mitochondrial contact sites in the subcellular compartmentalization of phospholipid biosynthetic enzymes. Ardail, D., Gasnier, F., Lermé, F., Simonot, C., Louisot, P., Gateau-Roesch, O. J. Biol. Chem. (1993) [Pubmed]
  11. A gender-specific role for phosphatidylethanolamine N-methyltransferase-derived phosphatidylcholine in the regulation of plasma high density and very low density lipoproteins in mice. Noga, A.A., Vance, D.E. J. Biol. Chem. (2003) [Pubmed]
  12. A role for hepatic scavenger receptor class B, type I in decreasing high density lipoprotein levels in mice that lack phosphatidylethanolamine N-methyltransferase. Robichaud, J.C., Francis, G.A., Vance, D.E. J. Biol. Chem. (2008) [Pubmed]
  13. Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins. Jacobs, R.L., Devlin, C., Tabas, I., Vance, D.E. J. Biol. Chem. (2004) [Pubmed]
  14. Gene expression profiling in phosphatidylethanolamine N-methyltransferase knockout mice. Zhu, X., Zeisel, S.H. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  15. Methyl balance and transmethylation fluxes in humans. Mudd, S.H., Brosnan, J.T., Brosnan, M.E., Jacobs, R.L., Stabler, S.P., Allen, R.H., Vance, D.E., Wagner, C. Am. J. Clin. Nutr. (2007) [Pubmed]
  16. Phosphatidylethanolamine N-methyltransferase (PEMT) knockout mice have hepatic steatosis and abnormal hepatic choline metabolite concentrations despite ingesting a recommended dietary intake of choline. Zhu, X., Song, J., Mar, M.H., Edwards, L.J., Zeisel, S.H. Biochem. J. (2003) [Pubmed]
  17. Localization of the PE methylation pathway and SR-BI to the canalicular membrane: evidence for apical PC biosynthesis that may promote biliary excretion of phospholipid and cholesterol. Sehayek, E., Wang, R., Ono, J.G., Zinchuk, V.S., Duncan, E.M., Shefer, S., Vance, D.E., Ananthanarayanan, M., Chait, B.T., Breslow, J.L. J. Lipid Res. (2003) [Pubmed]
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