Résumé
This study focuses on the phospholipid metabolism of the malaria parasite. It aims at developing new potent inhibitors targeting the rate-limiting enzyme of the phosphatidylcholine pathway and at deciphering the complex and interconnected pathways of the phospholipid metabolism in order to identify new relevant therapeutic targets for future development.Novel Aspect: Relative quantitation of labeled phospholipids to better understand the pathway of their biosynthesis in P. falciparum.Results: Previously, we identified the phospholipid precursors and the final phospholipid products of each pathway in P. falciparum by LC/MS/MS and quantified the relative contribution of each pathway to the biosynthesis of the three main phospholipids (PC, PE, and PS). Choline from serum was considered to be the only source of choline for the parasite. In this study, a labeled lysophosphatidylcholine is added with labeled choline, ethanolamine and serine in the serum. Our results suggest that the parasite uses almost exclusively lysophosphatidylcholine from serum to synthesize PC through the Kennedy pathway. Moreover, comparative lipidomics with a transgenic parasite line in which the gene encoding PMT activity is deleted clarified the interplay between the different pathways showing that P. falciparum is able to compensate for the lack of ethanolamine or serine by using lysophosphatidylcholine.