Linked Life Data

15664981

Source:http://linkedlifedata.com/resource/pubmed/id/15664981

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2005-3-28
pubmed:abstractText
Unlike humans and yeast, Plasmodium falciparum, the agent of the most severe form of human malaria, utilizes host serine as a precursor for the synthesis of phosphatidylcholine via a plant-like pathway involving phosphoethanolamine methylation. The monopartite phosphoethanolamine methyltransferase, Pfpmt, plays an important role in the biosynthetic pathway of this major phospholipid by providing the precursor phosphocholine via a three-step S-adenosyl-L-methionine-dependent methylation of phosphoethanolamine. In vitro studies showed that Pfpmt has strong specificity for phosphoethanolamine. However, the in vivo substrate (phosphoethanolamine or phosphatidylethanolamine) is not yet known. We used yeast as a surrogate system to express Pfpmt and provide genetic and biochemical evidence demonstrating the specificity of Pfpmt for phosphoethanolamine in vivo. Wild-type yeast cells, which inherently lack phosphoethanolamine methylation, acquire this activity as a result of expression of Pfpmt. The Pfpmt restores the ability of a yeast mutant pem1Deltapem2Delta lacking the phosphatidylethanolamine methyltransferase genes to grow in the absence of choline. Lipid analysis of the Pfpmt-complemented pem1Deltapem2Delta strain demonstrates the synthesis of phosphatidylcholine but not the intermediates of phosphatidylethanolamine transmethylation. Complementation of the pem1Deltapem2Delta mutant relies on specific methylation of phosphoethanolamine but not phosphatidylethanolamine. Interestingly, a mutation in the yeast choline-phosphate cytidylyltransferase gene abrogates the complementation by Pfpmt thus demonstrating that Pfpmt activity is directly coupled to the Kennedy pathway for the de novo synthesis of phosphatidylcholine.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12461-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15664981-Amino Acid Sequence, pubmed-meshheading:15664981-Animals, pubmed-meshheading:15664981-Base Sequence, pubmed-meshheading:15664981-Biochemical Phenomena, pubmed-meshheading:15664981-Biochemistry, pubmed-meshheading:15664981-Blotting, Western, pubmed-meshheading:15664981-Choline, pubmed-meshheading:15664981-Codon, pubmed-meshheading:15664981-Ethanolamines, pubmed-meshheading:15664981-Genetic Complementation Test, pubmed-meshheading:15664981-Genotype, pubmed-meshheading:15664981-Methyltransferases, pubmed-meshheading:15664981-Models, Biological, pubmed-meshheading:15664981-Molecular Sequence Data, pubmed-meshheading:15664981-Mutation, pubmed-meshheading:15664981-Phosphatidylcholines, pubmed-meshheading:15664981-Phosphatidylethanolamine N-Methyltransferase, pubmed-meshheading:15664981-Plasmodium falciparum, pubmed-meshheading:15664981-Protein Binding, pubmed-meshheading:15664981-S-Adenosylmethionine, pubmed-meshheading:15664981-Saccharomyces cerevisiae, pubmed-meshheading:15664981-Substrate Specificity, pubmed-meshheading:15664981-Temperature
pubmed:year
2005
pubmed:articleTitle
In vivo evidence for the specificity of Plasmodium falciparum phosphoethanolamine methyltransferase and its coupling to the Kennedy pathway.
pubmed:affiliation
Center for Microbial Pathogenesis and Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.