Review
Phospholipid methylation in mammals: from biochemistry to physiological function

https://doi.org/10.1016/j.bbamem.2013.10.018Get rights and content
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Highlights

  • Phosphatidylethanolamine N-methyltransferase from discovery to function is reviewed.

  • The enzyme is primarily regulated by supply of substrates.

  • Disruption of the PEMT gene results in an absolute requirement for dietary choline.

  • Lack of PEMT results in striking protection against obesity/insulin resistance.

Abstract

Phosphatidylcholine is made in the liver via the CDP-choline pathway and via the conversion of phosphatidylethanolamine to phosphatidylcholine by 3 transmethylation reactions from AdoMet catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). PEMT is a 22.3 kDa integral transmembrane protein of the endoplasmic reticulum and mitochondria-associated membranes. The only tissue with quantitatively significant PEMT activity is liver; however, low levels of PEMT in adipocytes have been implicated in lipid droplet formation. PEMT activity is regulated by the concentration of substrates (phosphatidylethanolamine and AdoMet) as well as the ratio of AdoMet to AdoHcy. Transcription of PEMT is enhanced by estrogen whereas the transcription factor Sp1 is a negative regulator of PEMT transcription. Studies with mice that lack PEMT have provided novel insights into the function of this enzyme. PEMT activity is required to maintain hepatic membrane integrity and for the formation of choline when dietary choline supply is limited. PEMT is required for normal secretion of very low-density lipoproteins. The lack of PEMT protects against diet-induced atherosclerosis in two mouse models. Most unexpectedly, mice that lack PEMT are protected from diet-induced obesity and insulin resistance. Moreover, mice lacking PEMT have increased susceptibility to diet-induced fatty liver and steatohepatitis. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.

Abbreviations

AdoMet
S-adenosylmethionine
AdoHcy
S-adenosylhomocysteine
ALT
alanine aminotransferase
CD
choline deficient
CT
CTP:phosphocholine cytidylyltransferase
ER
endoplasmic reticulum
Hcy
homocysteine
LCTαKO
liver-specific CTα knockout
LDL
low density lipoproteins
MAM
mitochondria-associated membranes
PC
phosphatidylcholine
PE
phosphatidylethanolamine
PEMT
phosphatidylethanolamine N-methyltransferase
TG
triacylglycerol
VLDL
very low density lipoproteins

Keywords

Phosphatidylcholine
Steatosis
Atherosclerosis
Choline
Homocysteine
Obesity

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This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.