6533b857fe1ef96bd12b4fcd

RESEARCH PRODUCT

Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway

Gerhard WunderlichBrenda Analía CirulliFernando G. De AlmeidaGerardo Cebrián-torrejónGerardo Cebrián-torrejónAntonio Doménech-carbóRaquel M. Simão-gurgeAlejandro M. KatzinEliana Fernanda Galindo CubillosJulia A. Cricco

subject

0301 basic medicineErythrocytesANIMAIS PARASITOS030231 tropical medicinePlasmodium falciparumProtozoan Proteinslcsh:MedicineHemePlasmodiumArticle03 medical and health scienceschemistry.chemical_compoundAntimalarials0302 clinical medicinePrenylationBiosynthesisBiophysical chemistryParasite physiologyparasitic diseasesHumansHeme O synthesislcsh:ScienceHemeGeneMultidisciplinaryAlkyl and Aryl TransferasesbiologyInhibitorslcsh:RPlasmodium falciparumbiology.organism_classificationHeme OElectron transport chainPlasmodium Falciparum030104 developmental biologychemistryBiochemistrylcsh:QPlasmodium parasitesAntimalarial drugs

description

A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the addition of these drugs. We conclude that heme O synthesis occurs in blood stage-P. falciparum and this pathway could be a potential target for antimalarial drugs. Fil: Simão-Gurge, Raquel M. University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology; Brazil Fil: Wunderlich, Gerhard. University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology; Brazil Fil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina. Fil: Galindo Cubillos, Eliana F. University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology; Brazil Fil: Domenech-Carbó, Antonio. University of Valencia. Faculty of Chemistry. Department of Analytical Chemistry; Spain Fil: Cebrián-Torrejón, Gerardo. University of Valencia. Faculty of Chemistry. Department of Analytical Chemistry; Spain Fil: Cebrián-Torrejón, Gerardo. Université des Antilles. Laboratoire COVACHIM-M2E EA 3592; France Fil: Almeida, Fernando G. University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology; Brazil Fil: Cirulli, Brenda Analía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina. Fil: Katzin, Alejandro M. University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology; Brazil

yearjournalcountryeditionlanguage
2019-12-01