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

dc.rights.licenseopenen_US
dc.contributor.authorWEIN, S.
dc.contributor.authorGHEZAL, S.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorBURE, Corinne
dc.contributor.authorMAYNADIER, M.
dc.contributor.authorPERIGAUD, C.
dc.contributor.authorVIAL, H. J.
dc.contributor.authorLEFEBVRE-TOURNIER, I.
dc.contributor.authorWENGELNIK, K.
dc.contributor.authorCERDAN, R.
dc.date.accessioned2020-04-07T14:00:56Z
dc.date.available2020-04-07T14:00:56Z
dc.date.issued2018
dc.identifier.issn0022-2275en_US
dc.identifier.otherhttps://www.jlr.org/content/59/8/1461/suppl/DC1en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/4153
dc.description.abstractEnThe 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-d(9), ethanolamine-d(4), and serine-d(3)) 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.
dc.language.isoENen_US
dc.subject.enPlasmodium falciparum
dc.subject.enKennedy pathway
dc.subject.enphosphatidylcholine
dc.subject.enphosphatidylethanolamine
dc.subject.enphosphatidylserine •lysophosphatidylcholine
dc.subject.enlipidomics
dc.subject.entandem mass spectrometry
dc.subject.enstable isotope tracers
dc.title.enContribution of the precursors and interplay of the pathways in the phospholipid metabolism of the malaria parasite
dc.typeArticle de revueen_US
dc.identifier.doi10.1194/jlr.M085589en_US
dc.subject.halChimie/Matériauxen_US
bordeaux.journalJournal of Lipid Researchen_US
bordeaux.page1461-1471en_US
bordeaux.volume59en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248
bordeaux.issue8en_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-02535449
hal.version1
hal.date.transferred2020-04-07T14:01:04Z
hal.exporttrue
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