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

• Published in: Journal of lipid research Vol. 59; no. 8; pp. 1461 - 1471
• Main Authors: Wein, Sharon, Ghezal, Salma, Buré, Corinne, Maynadier, Marjorie, Périgaud, Christian, Vial, Henri J., Lefebvre-Tournier, Isabelle, Wengelnik, Kai, Cerdan, Rachel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2018; Journal of Lipid Research; American Society for Biochemistry and Molecular Biology; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Adaptability; Chemical Sciences; Choline; Erythrocytes; Ethanolamine; Hemoglobin; Kennedy pathway; Lecithin; Lipid metabolism; lipidomics; Lysophosphatidylcholine; Malaria; Malaria, Falciparum - parasitology; Material chemistry; Metabolic Networks and Pathways; Metabolic pathways; Metabolism; Metabolites; Parasites; Phosphatidylcholine; Phosphatidylethanolamine; Phosphatidylserine; Phospholipids; Phospholipids - biosynthesis; Phospholipids - metabolism; Plasmodium falciparum; Plasmodium falciparum - metabolism; Plasmodium falciparum - physiology; Serine; stable isotope tracers; tandem mass spectrometry; Plasmodium falciparum; phosphatidylserine; lysophosphatidylcholine; phosphatidylethanolamine; tandem mass spectrometry; phosphatidylcholine; Kennedy pathway; lipidomics; stable isotope tracers; phosphatidylserine •lysophosphatidylcholine
• DOI: 10.1194/jlr.M085589
• ISSN: 0022-2275

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 of its PL synthesis pathways in response to different disturbances. These data provide new information by mapping the importance of the PL metabolic pathways of the malaria parasite and could be used to design future therapeutic approaches.