Artículo

Couto, A.S.; Caffaro, C.; Uhrig, M.L.; Kimura, E.; Peres, V.J.; Merino, E.F.; Katzin, A.M.; Neshioka, M.; Nonami, H.; Erra-Balsells, R. "Glycosphingolipids in Plasmodium falciparum: Presence of an active glucosylceramide synthase" (2004) European Journal of Biochemistry. 271(11):2204-2214
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Abstract:

Malaria remains a major health problem especially in tropical and subtropical regions of the world, and therefore developing new antimalarial drugs constitutes an urgent challenge. Lipid metabolism has been attracting a lot of attention as an application for malarial chemotherapeutic purposes in recent years. However, little is known about glycosphingolipid biosynthesis in Plasmodium falciparum. In this report we describe for the first time the presence of an active glucosylceramide synthase in the intraerythrocytic stages of the parasite. Two different experiments, using UDP-[14C]glucose as donor with ceramides as acceptors, or UDP-glucose as donor and fluorescent ceramides as acceptors, were performed. In both cases, we found that the parasitic enzyme was able to glycosylate only dihydroceramide. The enzyme activity could be inhibited in vitro with low concentrations of D,L-threo-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP). In addition, de novo biosynthesis of glycosphingolipids was shown by metabolic incorporation of [14C]palmitic acid and [14C]glucose in the three intraerythrocytic stages of the parasite. The structure of the ceramide, monohexosylceramide, trihexosylceramide and tetrahexosylceramide fractions was analysed by UV-MALDI-TOF mass spectrometry. When PPMP was added to parasite cultures, a correlation between arrest of parasite growth and inhibition of glycosphingolipid biosynthesis was observed. The particular substrate specificity of the malarial glucosylceramide synthase must be added to the already known unique and amazing features of P. falciparum lipid metabolism; therefore this enzyme might represent a new attractive target for malarial chemotherapy.

Registro:

Documento: Artículo
Título:Glycosphingolipids in Plasmodium falciparum: Presence of an active glucosylceramide synthase
Autor:Couto, A.S.; Caffaro, C.; Uhrig, M.L.; Kimura, E.; Peres, V.J.; Merino, E.F.; Katzin, A.M.; Neshioka, M.; Nonami, H.; Erra-Balsells, R.
Filiación:CIHIDECAR, Depto. de Quím. Orgán., Universidad de Buenos Aires, Argentina
Departamento de Parasitologia, Inst. de Ciê. Bioméd., Universidade de São Paulo, Brazil
College of Agriculture, Ehime University, Matsuyama, Japan
CIHIDECAR, Depto. de Quím. Orgán., Universidad de Buenos Aires, Buenos Aires, 1428, Argentina
Palabras clave:Dihydroceramide; Glucosylceramide synthase; Glycosphingolipids; Malaria; Plasmodium falciparum; carbon 14; ceramide derivative; ceramide glucosyltransferase; ceramide tetrahexoside; ceramide trihexoside; dihydroceramide; glucose; glycosphingolipid; monohexosylceramide; palmitic acid; unclassified drug; uridine diphosphate; article; biosynthesis; controlled study; correlation analysis; enzyme activity; enzyme specificity; in vitro study; lipid metabolism; matrix assisted laser desorption ionization time of flight mass spectrometry; nonhuman; parasite; Plasmodium falciparum; priority journal; Animals; Enzyme Inhibitors; Erythrocytes; Glucosyltransferases; Glycosphingolipids; Humans; Morpholines; Plasmodium falciparum; Protozoan Proteins; Sphingolipids; Substrate Specificity; Plasmodium falciparum; Protozoa
Año:2004
Volumen:271
Número:11
Página de inicio:2204
Página de fin:2214
DOI: http://dx.doi.org/10.1111/j.1432-1033.2004.04150.x
Título revista:European Journal of Biochemistry
Título revista abreviado:Eur. J. Biochem.
ISSN:00142956
CODEN:EJBCA
CAS:carbon 14, 14762-75-5; ceramide glucosyltransferase, 37237-44-8; glucose, 50-99-7, 84778-64-3; palmitic acid, 57-10-3; uridine diphosphate, 58-98-0; 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol; ceramide glucosyltransferase, EC 2.4.1.80; Enzyme Inhibitors; Glucosyltransferases, EC 2.4.1.-; Glycosphingolipids; Morpholines; Protozoan Proteins; Sphingolipids
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142956_v271_n11_p2204_Couto

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Citas:

---------- APA ----------
Couto, A.S., Caffaro, C., Uhrig, M.L., Kimura, E., Peres, V.J., Merino, E.F., Katzin, A.M.,..., Erra-Balsells, R. (2004) . Glycosphingolipids in Plasmodium falciparum: Presence of an active glucosylceramide synthase. European Journal of Biochemistry, 271(11), 2204-2214.
http://dx.doi.org/10.1111/j.1432-1033.2004.04150.x
---------- CHICAGO ----------
Couto, A.S., Caffaro, C., Uhrig, M.L., Kimura, E., Peres, V.J., Merino, E.F., et al. "Glycosphingolipids in Plasmodium falciparum: Presence of an active glucosylceramide synthase" . European Journal of Biochemistry 271, no. 11 (2004) : 2204-2214.
http://dx.doi.org/10.1111/j.1432-1033.2004.04150.x
---------- MLA ----------
Couto, A.S., Caffaro, C., Uhrig, M.L., Kimura, E., Peres, V.J., Merino, E.F., et al. "Glycosphingolipids in Plasmodium falciparum: Presence of an active glucosylceramide synthase" . European Journal of Biochemistry, vol. 271, no. 11, 2004, pp. 2204-2214.
http://dx.doi.org/10.1111/j.1432-1033.2004.04150.x
---------- VANCOUVER ----------
Couto, A.S., Caffaro, C., Uhrig, M.L., Kimura, E., Peres, V.J., Merino, E.F., et al. Glycosphingolipids in Plasmodium falciparum: Presence of an active glucosylceramide synthase. Eur. J. Biochem. 2004;271(11):2204-2214.
http://dx.doi.org/10.1111/j.1432-1033.2004.04150.x