HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 19, 17217-17225, May 10, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/19/17217    most recent M108911200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by DeLong, C. J. Articles by Cui, Z. Search for Related Content PubMed PubMed Citation Articles by DeLong, C. J. Articles by Cui, Z. Social Bookmarking                      What's this?

Disruption of Choline Methyl Group Donation for Phosphatidylethanolamine Methylation in Hepatocarcinoma Cells^*

Cynthia J. DeLong^§, Amy M. Hicks^§, and Zheng Cui^**

From the Departments of  Biochemistry and  Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Despite being widely hypothesized, the actual contribution of choline as a methyl source for phosphatidylethanolamine (PE) methylation has never been demonstrated, mainly due to the inability of conventional methods to distinguish the products from that of the CDP-choline pathway. Using a novel combination of stable-isotope labeling and tandem mass spectrometry, we demonstrated for the first time that choline contributed to phosphatidylcholine (PC) synthesis both as an intact choline moiety via the CDP-choline pathway and as a methyl donor via PE methylation pathway. When hepatocytes were labeled with d₉-choline containing three deuterium atoms on each of the three methyl groups, d₃-PC and d₆-PC were detected, indicating that newly synthesized PC contained one or more individually mobilized methyl groups from d₉-choline. The synthesis of d₃-PC and d₆-PC was sensitive to the general methylation inhibitor 3-deazaadenosine and were specific products of PE methylation using choline as a one-carbon donor. While the contribution to the CDP-choline pathway remained intact in hepatocarcinoma cells, contribution of choline to PE methylation was completely disrupted. In addition to a previously identified lack of PE methyltransferase, hepatocarcinoma cells were found to lack the abilities to oxidize choline to betaine and to donate the methyl group from betaine to homocysteine, whereas the usage of exogenous methionine as a methyl group donor was normal. The failure to use choline as a methyl source in hepatocarcinoma cells may contribute to methionine dependence, a widely observed aberration of one-carbon metabolism in malignancy.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati