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Biochim Biophys Acta. 2014 Jun;1838(6):1477-87. doi: 10.1016/j.bbamem.2013.10.018. Epub 2013 Nov 1.

Phospholipid methylation in mammals: from biochemistry to physiological function.

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1
Group on the Molecular and Cell Biology of Lipids, Department of Biochemistry, Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dennis.vance@ualberta.ca.

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 22.3kDa 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.

KEYWORDS:

Atherosclerosis; Choline; Homocysteine; Obesity; Phosphatidylcholine; Steatosis

PMID:
24184426
DOI:
10.1016/j.bbamem.2013.10.018
[Indexed for MEDLINE]
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