Linked Life Data

15927961

Source:http://linkedlifedata.com/resource/pubmed/id/15927961

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2005-7-19
pubmed:abstractText
Genetic ablation of phosphatidylethanolamine N-methyltransferase (PEMT) in mice causes a 50% reduction in plasma homocysteine (Hcy) levels. Because hyperhomocysteinemia is an independent risk factor for cardiovascular disease, resolution of the molecular basis for this reduction is of significant clinical interest. The PEMT pathway is a metabolically channeled process localized to the endoplasmic reticulum (ER). To assess the importance of PEMT localization for Hcy homeostasis, we identified and ablated the minimal ER targeting motif. Mutagenesis of a conserved, C-terminal lysine residue (197) relocalized the enzyme to the Golgi, demonstrating that Lys-197 is essential for targeting PEMT to the ER. To evaluate the functional significance of PEMT localization, hepatoma cell lines were generated that stably expressed either ER- or Golgi-localized PEMT only. Intriguingly, stable expression of PEMT in either the ER or the Golgi caused increased Hcy secretion. Moreover, PEMT-mediated Hcy secretion correlated with the methyltransferase activity of the enzyme, independently of subcellular localization. Thus, our data suggest that Hcy homeostasis is regulated concomitantly with PEMT activity but independently of PEMT localization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27339-44
pubmed:dateRevised
2008-5-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Localization-independent regulation of homocysteine secretion by phosphatidylethanolamine N-methyltransferase.
pubmed:affiliation
Department of Biochemistry and Canadian Institutes of Health Research Group on Molecular & Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't