On the mechanism of hemozoin production in malaria parasites:: Activated erythrocyte membranes promote β-hematin synthesis

The ferriprotoporphyrin IX (FP) molecules released by intraerythrocytic malaria parasites during hemoglobin digestion are converted to beta -hematin and are stored in the parasites' food vacuoles. It has been demonstrated in cell-free medium that the incorporation of FP into beta -hematin under physiological conditions requires a catalyst from parasite lysates or pre-formed beta -hematin. In the present studies, lysates of Plasmodium falciparum-infected erythrocytes were suspended in I M NaOH and were washed with phosphate buffer, pH 7.6. When the cell extracts were incubated with hematin in 0.5 M sodium acetate buffer, pH 5, for 20 hr at 37 degreesC, a large quantity of beta -hematin was formed. To determine whether parasite components were necessary for the beta -hematin formation, normal erythrocyte ghosts were similarly treated with 1 M NaOH and then incubated with hematin. In repeated experiments it was found that, on the average, 70% of the hematin was converted to beta -hematin. Membranes treated with HCl or CH3COOH also promoted the formation of beta -hematin, while untreated membranes were ineffective. The possibility that metabolic activities in the food vacuoles of malaria parasites may activate membrane fragments, from hemoglobin vesicles, to promote beta -hematin formation is discussed in this paper.