Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: presence of dolichols of 11 and 12 isoprene units

Autor: Alejandro M. Katzin, María Laura Uhrig, Alicia S. Couto, Emilia A. Kimura, Valnice J. Peres
Rok vydání: 1999
Předmět:
Zdroj: Biochemical Journal. 341:629-637
ISSN: 1470-8728
0264-6021
DOI: 10.1042/bj3410629
Popis: 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.
Databáze: OpenAIRE