Inhibition of glycosylphosphatidylinositol biosynthesis in Leishmania mexicana by mannosamine.
In several Leishmania species, glycosylated inositol phospholipids exist as free lipids, as membrane protein anchors, and as the membrane-binding moieties of the lipophosphoglycans. Both the glycolipid-anchored cell surface metalloproteinase, gp63, and the lipophosphoglycans have been proposed to be involved in cell invasion. Moreover, the lipophosphoglycans have been implicated in the survival of Leishmania in the parasitophorous vacuole of the host macrophage. In this report we show that mannosamine effectively inhibits the biosynthesis of both free glycosylated inositol phospholipids and the lipophosphoglycans of Leishmania mexicana. [3H]Mannosamine is incorporated into glycosylated inositol phospholipids, but not significantly into lipophosphoglycans when added as a radiochemical tracer at a subinhibitory concentration. The reversible inhibitory effect of mannosamine may be useful for studying precursor/product relationships during the biosynthesis of free glycosylated inositol phospholipids, glycolipid anchors, and the lipophosphoglycans. The implications of these data for the mode of action of mannosamine are discussed.
Field
M C
MC
Laboratory of Molecular Parasitology, Rockefeller University, New York, New York 10021-6399.
Medina-Acosta
E
E
Cross
G A
GA
D000818:Animals; D002855:Chromatography, Thin Layer; D019856:Ethanolamine; D004983:Ethanolamines; D005690:Galactose / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006028:Glycosphingolipids / Q000096:biosynthesis* / Q000302:isolation & purification; D017261:Glycosylphosphatidylinositols / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006595:Hexosamines / Q000378:metabolism* / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D007894:Leishmania mexicana / Q000187:drug effects / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014316:Tritium
D004983:Ethanolamines; D006028:Glycosphingolipids; D017261:Glycosylphosphatidylinositols; D006595:Hexosamines; D007295:Inositol Phosphates; D013462:Sulfur Radioisotopes; C008290:lipophosphonoglycan; D014316:Tritium; C008322:mannosamine; D019856:Ethanolamine; D008715:Methionine; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D005944:Glucosamine; D005690:Galactose