Characterization of the isoprenoid chain of coenzyme Q in Plasmodium falciparum.
Little is known about isoprenoid biosynthesis in parasitic protozoa. The presence of dolichol and isoprenylated proteins has been detected in Plasmodium falciparum, but no studies are available about the biosynthesis of the isoprenic side chain attached to the benzoquinone ring of coenzyme Q. In the present study, using metabolic labelling with different intermediates, we demonstrated the presence of an active isoprenoid pathway for the biosynthesis of the isoprenic chain of coenzyme Q. Our results show that P. falciparum is able to synthesize different homologs (coenzyme Q(8) and coenzyme Q(9)), depending on the given intermediate. Parasites treated with nerolidol at doses 2.2 times below the IC(50) showed a decreased ability to synthesize the isoprenic chain attached to coenzyme Q at all intraerythrocytic stages. Treatment with nerolidol arrested development of the intraerythrocytic stages of the parasites, indicating that the drug may have an antimalarial potential.
de Macedo
Cristiana Santos
CS
Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes 1374, CEP 05508-900, SP, Brazil.
Uhrig
Maria Laura
ML
Kimura
Emilia A
EA
Katzin
Alejandro Miguel
AM
D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D011106:Polyisoprenyl Phosphates / Q000737:chemistry* / Q000378:metabolism*; D017368:Protein Prenylation; D012717:Sesquiterpenes / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism; D014451:Ubiquinone / Q000096:biosynthesis* / Q000737:chemistry
D002250:Carbon Radioisotopes; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D014316:Tritium; D014451:Ubiquinone; C037055:nerolidol