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Abstract:

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.

Registro:

Documento: Artículo
Título:Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units
Autor:Couto, A.S.; Kimura, E.A.; Peres, V.J.; Uhrig, M.L.; Katzin, A.M.
Filiación:CIHIDECAR, Depto. de Quimica Organica, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Departamento de Parasitologia, Inst. de Ciências Biomedicas, Universidade de São Paulo, Av. Lineu Prestes 1374, CEP 05508-900, São Paulo SP, Brazil
Palabras clave:[1(n)-3H]farnesyl triammonium pyrophosphate; [1(n)-3H]geranylgeranyl triammonium pyrophosphate; Malaria; Mevastatin; acetic acid; carbon 14; compactin; dolichol; dolichol phosphate; hydroxymethylglutaryl coenzyme a reductase; isoprenoid; pyrophosphoric acid derivative; tritium; article; biosynthesis; controlled study; erythrocyte; human; isotope labeling; life cycle; nonhuman; plasmodium falciparum; priority journal; protein glycosylation; trophozoite; Animals; Dolichol; Erythrocytes; Glycoproteins; Lovastatin; Plasmodium falciparum; Apicomplexa; Eukaryota; Plasmodium falciparum; Tritium
Año:1999
Volumen:341
Número:3
Página de inicio:629
Página de fin:637
DOI: http://dx.doi.org/10.1042/0264-6021:3410629
Título revista:Biochemical Journal
Título revista abreviado:Biochem. J.
ISSN:02646021
CODEN:BIJOA
CAS:compactin, 73573-88-3; Dolichol, 2067-66-5; Glycoproteins; Lovastatin, 75330-75-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v341_n3_p629_Couto

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Citas:

---------- APA ----------
Couto, A.S., Kimura, E.A., Peres, V.J., Uhrig, M.L. & Katzin, A.M. (1999) . Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units. Biochemical Journal, 341(3), 629-637.
http://dx.doi.org/10.1042/0264-6021:3410629
---------- CHICAGO ----------
Couto, A.S., Kimura, E.A., Peres, V.J., Uhrig, M.L., Katzin, A.M. "Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units" . Biochemical Journal 341, no. 3 (1999) : 629-637.
http://dx.doi.org/10.1042/0264-6021:3410629
---------- MLA ----------
Couto, A.S., Kimura, E.A., Peres, V.J., Uhrig, M.L., Katzin, A.M. "Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units" . Biochemical Journal, vol. 341, no. 3, 1999, pp. 629-637.
http://dx.doi.org/10.1042/0264-6021:3410629
---------- VANCOUVER ----------
Couto, A.S., Kimura, E.A., Peres, V.J., Uhrig, M.L., Katzin, A.M. Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units. Biochem. J. 1999;341(3):629-637.
http://dx.doi.org/10.1042/0264-6021:3410629