Plasmodium falciparum-infected erythrocytes utilize a synthetic truncated ceramide precursor for synthesis and secretion of truncated sphingomyelin.
Plasmodium falciparum is an intracellular parasite of human erythrocytes. Parasite development is accompanied by an increase of the phospholipid content of the infected erythrocyte, but it results in a selective decrease of sphingomyelin. We have studied sphingomyelin biosynthesis in infected erythrocytes using as substrate a synthetic radiolabelled ceramide precursor, truncated in both hydrophobic chains. Lysates of infected, unlike those of non-infected, erythrocytes contained sphingomyelin synthase activity, which therefore is of parasite origin. The enzyme activity was associated with a membrane fraction. In contrast to mammalian cells, the parasite did not synthesize detectable levels of glycosphingolipids. In intact infected erythrocytes the ceramide precursor was converted into a correspondingly truncated soluble sphingomyelin which was released into the medium at 37 degrees C. Release of truncated sphingomyelin was inhibited by low temperature (15 degrees C) but not by the fungal metabolite brefeldin A which, however, arrests protein export from the parasite. While membranes of mammalian cells, including the plasma membrane of non-infected erythrocytes, are impermeable to truncated sphingomyelin, the membrane of infected erythrocytes allowed passage of the molecule in both directions. The results obtained with the unicellular eukaryote used here as an experimental model are discussed in comparison with sphingomyelin synthesis and transport in mammalian cells.
Ansorge
I
I
Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany.
Jeckel
D
D
Wieland
F
F
Lingelbach
K
K
D000818:Animals; D020126:Brefeldin A; D002463:Cell Membrane Permeability; D002518:Ceramides / Q000737:chemistry / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D066298:In Vitro Techniques; D016778:Malaria, Falciparum / Q000201:enzymology*; D010963:Plasmodium falciparum; D013109:Sphingomyelins / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism
D002518:Ceramides; D003517:Cyclopentanes; D013109:Sphingomyelins; D020126:Brefeldin A; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase