Oleic Acid Biosynthesis in Plasmodium falciparum Characterization of the Stearoyl-CoA Desaturase and Investigation as a Potential Therapeutic Target 英文参考文献.docVIP

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Oleic Acid Biosynthesis in Plasmodium falciparum Characterization of the Stearoyl-CoA Desaturase and Investigation as a Potential Therapeutic Target 英文参考文献.doc

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Oleic Acid Biosynthesis in Plasmodium falciparum Characterization of the Stearoyl-CoA Desaturase and Investigation as a Potential Therapeutic Target 英文参考文献

OleicAcidBiosynthesisinPlasmodiumfalciparum: CharacterizationoftheStearoyl-CoADesaturaseand InvestigationasaPotentialTherapeuticTarget PaulGratraud1,EnlliHuws2,BrieFalkard3,SophieAdjalley3,DavidA.Fidock3,4,LaurenceBerry1, WilliamR.Jacobs,Jr.5,6,MarkS.Baird2,HenriVial1,7,LaurentKremer1,7 * 1LaboratoiredeDynamiquedesInteractionsMembranairesNormalesetPathologiques,Universite′sdeMontpellierIIetI,CNRS,UMR5235,case107,Montpellier,France, 2SchoolofChemistry,BangorUniversity,Bangor,Wales,3DepartmentofMicrobiology,CollegeofPhysiciansandSurgeons,ColumbiaUniversity,NewYork,NewYork, UnitedStatesofAmerica,4DepartmentofMedicine,CollegeofPhysiciansandSurgeons,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica,5Howard HughesMedicalInstitute,AlbertEinsteinCollegeofMedicine,Bronx,NewYork,UnitedStatesofAmerica,6DepartmentofMicrobiologyandImmunology,AlbertEinstein CollegeofMedicine,Bronx,NewYork,UnitedStatesofAmerica,7INSERM,DIMNP,Montpellier,France Abstract Background:Plasmodiumfalciparumparasitizationoferythrocytescausesasubstantialincreaseinthelevelsofintracellular fatty acids, notably oleic acid. How parasites acquire this monounsaturated fatty acid has remained enigmatic. Here, we reportonthebiochemicalandenzymaticcharacterizationofstearoyl-CoAdesaturase(SCD)inP.falciparum. Methodology/PrincipalFindings:Metaboliclabelingexperimentsallowedustodemonstratetheproductionofoleicacid fromstearicacidbothinlysatesofparasitesincubatedwith[14C]-stearoyl-CoAandinparasite-infectederythrocyteslabeled with [14C]-stearic acid. Optimal SCD activity was detected in schizonts, the stage of maximal membrane synthesis. This activitycorrelatedwithalatetrophozoitestage-specificinductionofPFE0555wtranscripts.PFE0555wharborsatypicalSCD signature. Similar to mammalian SCDs, this protein was found to be associated with the endoplasmic reticulum, as determinedwithPFE0555w-GFPtaggedtransgenicP.falciparum.Importantly,theseparasitesexhibitedincreasedratesof stearictooleicacidconversion,providingaddition