N-glycosylation of proteins is required for the intra-erythrocytic schizogony of Plasmodium falciparum. In eukaryotic cells, this process involves the transfer of oligosaccharides from a dolichyl pyrophosphate derivative to asparagine residues. We have identified dolichol, dolichyl phosphate and dolichyl pyrophosphate species of 11 and 12 isoprenoid residues by metabolic labelling with [3H]farnesyl pyrophosphate, [3H]geranylgeranyl pyrophosphate and [14C]acetate in the different intra-erythrocytic stages of P. falciparum. This is the first demonstration of short-chain dolichols in the phylum Apicomplexa. The results demonstrate the presence of an active isoprenoid pathway in the intra-erythrocytic stages of P. falciparum. Parasites treated with mevastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, show depressed biosynthesis of dolichol, dolichyl phosphate and isoprenoid pyrophosphate. This effect is observed in all intra-erythrocytic stages of the parasite life cycle, but is most pronounced in the ring stage. N-linked glycosylation of proteins was inhibited in the ring and young-trophozoite stages after mevastatin treatment of parasite cultures. Therefore the isoprenoid pathway may represent a different approach to the development of new anti-malarial drugs.
Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: presence of dolichols of 11 and 12 isoprene units
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Alicia S. COUTO, Emilia A. KIMURA, Valnice J. PERES, Maria L. UHRIG, Alejandro M. KATZIN; Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: presence of dolichols of 11 and 12 isoprene units. Biochem J 1 August 1999; 341 (3): 629–637. doi: https://doi.org/10.1042/bj3410629
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