Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units
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 dol...
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todo:paper_02646021_v341_n3_p629_Couto2023-10-03T15:12:59Z Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units Couto, A.S. Kimura, E.A. Peres, V.J. Uhrig, M.L. Katzin, A.M. [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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02646021_v341_n3_p629_Couto |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
[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 |
| spellingShingle |
[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 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 |
| topic_facet |
[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 |
| description |
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. |
| format |
JOUR |
| author |
Couto, A.S. Kimura, E.A. Peres, V.J. Uhrig, M.L. Katzin, A.M. |
| author_facet |
Couto, A.S. Kimura, E.A. Peres, V.J. Uhrig, M.L. Katzin, A.M. |
| author_sort |
Couto, A.S. |
| title |
Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units |
| title_short |
Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units |
| title_full |
Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units |
| title_fullStr |
Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units |
| title_full_unstemmed |
Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units |
| title_sort |
active isoprenoid pathway in the intra-erythrocytic stages of plasmodium falciparum: presence of dolichols of 11 and 12 isoprene units |
| url |
http://hdl.handle.net/20.500.12110/paper_02646021_v341_n3_p629_Couto |
| work_keys_str_mv |
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