Contribution of the precursors and interplay of the pathways in the phospholipid metabolism of the malaria parasite.

Journal of Lipid Research
Sharon WeinRachel Cerdan

Abstract

The malaria parasite, Plasmodium falciparum, develops and multiplies in the human erythrocyte. It needs to synthesize considerable amounts of phospholipids (PLs), principally phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). Several metabolic pathways coexist for their de novo biosynthesis, involving a dozen enzymes. Given the importance of these PLs for the survival of the parasite, we sought to determine their sources and to understand the connections and dependencies between the multiple pathways. We used three deuterated precursors (choline-d9, ethanolamine-d4, and serine-d3) to follow and quantify simultaneously their incorporations in the intermediate metabolites and the final PLs by LC/MS/MS. We show that PC is mainly derived from choline, itself provided by lysophosphatidylcholine contained in the serum. In the absence of choline, the parasite is able to use both other precursors, ethanolamine and serine. PE is almost equally synthesized from ethanolamine and serine, with both precursors being able to compensate for each other. Serine incorporated in PS is mainly derived from the degradation of host cell hemoglobin by the parasite. P. falciparum thus shows an unexpected adaptability o...Continue Reading

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Citations

Oct 6, 2018·The Journal of Biological Chemistry·Nicole KilianChoukri Ben Mamoun
Jul 17, 2020·Nature Communications·Aditya S PaulManoj T Duraisingh
Oct 30, 2020·ELife·Anya J O'NealJoao Hf Pedra
Nov 26, 2020·Molecular Microbiology·Manish KumarManoj T Duraisingh
Jul 1, 2019·Bioorganic & Medicinal Chemistry Letters·Olivier BergerYen Vo-Hoang
Aug 31, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Margarida Ressurreição, Christiaan van Ooij

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Methods Mentioned

BETA
transgenic
light microscopy
acylation

Software Mentioned

Lipid View
MultiQuant

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