Neutral sphingomyelinase activity dependent on Mg2+ and anionic phospholipids in the intraerythrocytic malaria parasite Plasmodium falciparum

Sphingolipid metabolism and metabolites are important in various cellular e vents in eukaryotes. However, little is known about their function in plasm odial parasites. Here we demonstrate that neutral sphingomyelinase (SMase) involved in the sphingomyelin (SM) catabolism is retained by the intraeryth rocytic parasite Plasmodium falciparum llnl. When assayed in a neutral pH b uffer supplemented with Mg2+ and phosphatidylserine, an activity for the re lease of the phosphocholine group from SM was detected in parasite-infected , but not in uninfected, erythrocyte ghosts. The SMase activity in the para site-infected erythrocyte ghosts was enhanced markedly by anionic phospholi pids including unsaturated but not saturated phosphatidylserine. Mn2+ could not substitute for Mg2+ to activate SMase in parasite-infected erythrocyte ghosts, whereas both Mn2+ and Mg2+ activated mammalian neutral SMase. The specific activity level of SMase was higher in isolated parasites than in i nfected erythrocyte ghosts; further fractionation of lysates of the isolate d parasites showed that the activity was bound largely to the membrane frac tion of the parasites. The plasmodial SMase seemed not to hydrolyse phospha tidylcholine or phosphatidylinositol. The plasmodial SMase, but not SM synt hase, was sensitive to scyphostatin an inhibitor of mammalian neutral SMase , indicating that the plasmodial activities for SM hydrolysis and SM synthe sis are mediated by different catalysts. Our finding that the malaria paras ites possess SMase activity might explain why the parasites seem to have an SM synthase activity but no activity to synthesize ceramide de novo.