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 erythrocyt es. Parasite development is accompanied by an increase of the phosphol ipid content of the infected erythrocyte, but it results in a selectiv e decrease of sphingomyelin. We have studied sphingomyelin biosynthesi s in infected erythrocytes using as substrate a synthetic radiolabelle d ceramide precursor, truncated in both hydrophobic chains. Lysates of infected, unlike those of non-infected, erythrocytes contained sphing omyelin synthase activity, which therefore is of parasite origin, The enzyme activity was associated with a membrane fraction. In contrast t o mammalian cells, the parasite did not synthesize detectable levels o f glycosphingolipids, In intact infected erythrocytes the ceramide pre cursor was converted into a correspondingly truncated soluble sphingom yelin which was released into the medium at 37 degrees C. Release of t runcated 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 imperm eable to truncated sphingomyelin, the membrane of infected erythrocyte s allowed passage of the molecule in both directions. The results obta ined with the unicellular eukaryote used here as an experimental model are discussed in comparison with sphingomyelin synthesis and transpor t in mammalian cells.