title: Mitochondrial NADH dehydrogenase from Plasmodium falciparum and Plasmodium berghei.
abstract: The mitochondrial electron transport system is necessary for growth and survival of malarial parasites in mammalian host cells. NADH dehydrogenase of respiratory complex I was demonstrated in isolated mitochondrial organelles of the human parasite Plasmodium falciparum and the mouse parasite Plasmodium berghei by using the specific inhibitor rotenone on oxygen consumption and enzyme activity. It was partially purified by two sequential steps of fast protein liquid chromatographic techniques from n-octyl glucoside solubilization of the isolated mitochondria of both parasites. In addition, physical and kinetic properties of the malarial enzymes were compared to the host mouse liver mitochondrial respiratory complex I either as intact or as partially purified forms. The malarial enzyme required both NADH and ubiquinone for maximal catalysis. Furthermore, rotenone and plumbagin (ubiquinone analog) showed strong inhibitory effect against the purified malarial enzymes and had antimalarial activity against in vitro growth of P. falciparum. Some unique properties suggest that the enzyme could be exploited as chemotherapeutic target for drug development, and it may have physiological significance in the mitochondrial metabolism of the parasite.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Rama 4 Rd., Bangkok 10330, Thailand. fmedjkk@md2.md.chula.ac.th
authors.forename: Jerapan
authors.initials: J
authors.lastname: Krungkrai
authors.forename: Rachanok
authors.initials: R
authors.lastname: Kanchanarithisak
authors.forename: Sudaratana R
authors.initials: SR
authors.lastname: Krungkrai
authors.forename: Sunant
authors.initials: S
authors.lastname: Rochanakij
mesh_terms: D000818:Animals; D006801:Humans; D007700:Kinetics; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D009245:NADH Dehydrogenase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010101:Oxygen Consumption; D010962:Plasmodium berghei / Q000201:enzymology* / Q000648:ultrastructure; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D009245:NADH Dehydrogenase