| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 5, 2956-2962, January 31, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Departments of Biochemistry, Pediatrics and Cell Biology
and Canadian Institutes of Health Research Group on Molecular and
Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G
2S2, Canada
In liver, phosphatidylethanolamine is
converted to phosphatidylcholine through a series of three sequential
methylation reactions. Phosphatidylethanolamine
N-methyltransferase (PEMT) catalyzes each
transmethylation reaction, and
S-adenosylmethionine is the methyl group donor.
Biochemical analysis of human liver revealed that the methyltransferase
activity is primarily localized to the endoplasmic reticulum and
mitochondria-associated membranes. Bioinformatic analysis of the
predicted amino acid sequence suggested that the enzyme adopts a
polytopic conformation in those membranes. To elucidate the precise
membrane topography of PEMT and thereby provide the basis for in-depth
functional characterization of the enzyme, we performed
endoproteinase-protection analysis of epitope-tagged, recombinant
protein. Our data suggest a topographical model of PEMT in which four
transmembrane regions span the membrane such that both the N and C
termini of the enzyme are localized external to the ER. Two hydrophilic
connecting loops protrude into the luminal space of the microsomes
whereas a corresponding loop on the cytosolic side remains proximate to
the membrane. Further support for this model was obtained following
endoproteinase-protection analysis of mutant recombinant PEMT
derivatives in which specific protease cleavage sites had been
genetically engineered or ablated.
Membrane Topography of Human Phosphatidylethanolamine
N-Methyltransferase*
,
*
This research was supported by a grant from the Canadian
Institutes for Health Research. Ethics approval for work on human tissues was obtained from the Health Research Ethics board at the
University of Alberta.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by a Studentship from the Alberta Heritage Foundation
for Medical Research.
§
Scholar of the Alberta Heritage Foundation for Medical Research.
¶
Senior Scholar of the Alberta Heritage Foundation for Medical Research.
Canada Research Chair in Molecular and Cell Biology of Lipids
and Heritage Medical Scientist of the Alberta Heritage Foundation for
Medical Research. To whom correspondence should be addressed: 328 HMRC, Dept. of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Tel.: 780-492-8286; Fax:
780-492-3383; E-mail: Dennis.Vance@ualberta.ca.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Li and D. E. Vance Thematic Review Series: Glycerolipids. Phosphatidylcholine and choline homeostasis J. Lipid Res., June 1, 2008; 49(6): 1187 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Vance, Z. Li, and R. L. Jacobs Hepatic Phosphatidylethanolamine N-Methyltransferase, Unexpected Roles in Animal Biochemistry and Physiology J. Biol. Chem., November 16, 2007; 282(46): 33237 - 33241. [Full Text] [PDF]
|
|
|
|
 |
|
 S H. Mudd, J. T Brosnan, M. E Brosnan, R. L Jacobs, S. P Stabler, R. H Allen, D. E Vance, and C. Wagner Methyl balance and transmethylation fluxes in humans Am. J. Clinical Nutrition, January 1, 2007; 85(1): 19 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Shields, S. Lingrell, L. B. Agellon, J. T. Brosnan, and D. E. Vance Localization-independent Regulation of Homocysteine Secretion by Phosphatidylethanolamine N-Methyltransferase J. Biol. Chem., July 22, 2005; 280(29): 27339 - 27344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pottekat and A. K. Menon Subcellular Localization and Targeting of N-Acetylglucosaminyl Phosphatidylinositol De-N-acetylase, the Second Enzyme in the Glycosylphosphatidylinositol Biosynthetic Pathway J. Biol. Chem., April 16, 2004; 279(16): 15743 - 15751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Shields, J. Y. Altarejos, X. Wang, L. B. Agellon, and D. E. Vance Molecular Dissection of the S-Adenosylmethionine-binding Site of Phosphatidylethanolamine N-Methyltransferase J. Biol. Chem., September 12, 2003; 278(37): 35826 - 35836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sehayek, R. Wang, J. G. Ono, V. S. Zinchuk, E. M. Duncan, S. Shefer, D. E. Vance, M. Ananthanarayanan, B. T. Chait, and J. L. Breslow 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 J. Lipid Res., September 1, 2003; 44(9): 1605 - 1613. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
