Disruption of the Plasmodium falciparum PfPMT gene results in a complete loss of phosphatidylcholine biosynthesis via the serine-decarboxylase- phosphoethanolamine-methyltransferase pathway and severe growth and survival defects

William Harold Witola, Kamal El Bissati, Gabriella Pessi, Changan Xie, Paul D. Roepe, Choukri Ben Mamoun

Research output: Contribution to journalArticle

Abstract

Biochemical studies in the human malaria parasite, Plasmodium falciparum, indicated that in addition to the pathway for synthesis of phosphatidylcholine from choline (CDP-choline pathway), the parasite synthesizes this major membrane phospholipid via an alternative pathway named the serine-decarboxylase- phosphoethanolamine-methyltransferase (SDPM) pathway using host serine and ethanolamine as precursors. However, the role the transmethylation of phosphatidylethanolamine plays in the biosynthesis of phosphatidylcholine and the importance of the SDPM pathway in the parasite's growth and survival remain unknown. Here, we provide genetic evidence that knock-out of the PfPMT gene encoding the phosphoethanolamine methyltransferase enzyme completely abrogates the biosynthesis of phosphatidylcholine via the SDPM pathway. Lipid analysis in knock-out parasites revealed that unlike in mammalian and yeast cells, methylation of phosphatidylethanolamine to phosphatidylcholine does not occur in P. falciparum, thus making the SDPM and CDP-choline pathways the only routes for phosphatidylcholine biosynthesis in this organism. Interestingly, loss of PfPMT resulted in significant defects in parasite growth, multiplication, and viability, suggesting that this gene plays an important role in the pathogenesis of intraerythrocytic Plasmodium parasites.

Original languageEnglish (US)
Pages (from-to)27636-27643
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number41
DOIs
StatePublished - Oct 10 2008
Externally publishedYes

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Carboxy-Lyases
Methyltransferases
Plasmodium falciparum
Phosphatidylcholines
Serine
Parasites
Genes
Biosynthesis
Erythrasma
Cytidine Diphosphate Choline
Methacholine Compounds
Cyclic AMP Receptor Protein
Defects
Gene Knockout Techniques
Ethanolamine
Plasmodium
Falciparum Malaria
Choline
Methylation
Phospholipids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Disruption of the Plasmodium falciparum PfPMT gene results in a complete loss of phosphatidylcholine biosynthesis via the serine-decarboxylase- phosphoethanolamine-methyltransferase pathway and severe growth and survival defects. / Witola, William Harold; El Bissati, Kamal; Pessi, Gabriella; Xie, Changan; Roepe, Paul D.; Mamoun, Choukri Ben.

In: Journal of Biological Chemistry, Vol. 283, No. 41, 10.10.2008, p. 27636-27643.

Research output: Contribution to journalArticle

Witola, William Harold; El Bissati, Kamal; Pessi, Gabriella; Xie, Changan; Roepe, Paul D.; Mamoun, Choukri Ben / Disruption of the Plasmodium falciparum PfPMT gene results in a complete loss of phosphatidylcholine biosynthesis via the serine-decarboxylase- phosphoethanolamine-methyltransferase pathway and severe growth and survival defects.

In: Journal of Biological Chemistry, Vol. 283, No. 41, 10.10.2008, p. 27636-27643.

Research output: Contribution to journalArticle

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abstract = "Biochemical studies in the human malaria parasite, Plasmodium falciparum, indicated that in addition to the pathway for synthesis of phosphatidylcholine from choline (CDP-choline pathway), the parasite synthesizes this major membrane phospholipid via an alternative pathway named the serine-decarboxylase- phosphoethanolamine-methyltransferase (SDPM) pathway using host serine and ethanolamine as precursors. However, the role the transmethylation of phosphatidylethanolamine plays in the biosynthesis of phosphatidylcholine and the importance of the SDPM pathway in the parasite's growth and survival remain unknown. Here, we provide genetic evidence that knock-out of the PfPMT gene encoding the phosphoethanolamine methyltransferase enzyme completely abrogates the biosynthesis of phosphatidylcholine via the SDPM pathway. Lipid analysis in knock-out parasites revealed that unlike in mammalian and yeast cells, methylation of phosphatidylethanolamine to phosphatidylcholine does not occur in P. falciparum, thus making the SDPM and CDP-choline pathways the only routes for phosphatidylcholine biosynthesis in this organism. Interestingly, loss of PfPMT resulted in significant defects in parasite growth, multiplication, and viability, suggesting that this gene plays an important role in the pathogenesis of intraerythrocytic Plasmodium parasites.",
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