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ORIGINAL ARTICLE

On the Mechanism of Hemozoin Production in Malaria Parasites: Activated Erythrocyte Membranes Promote ß-Hematin Synthesis

Faculty of Allied Health Sciences, Kuwait University, Salaibikhat 90805, Kuwait

The ferriprotoporphyrin IX (FP) molecules released by intraerythrocytic malaria parasites during hemoglobin digestion are converted to ß-hematin and are stored in the parasites' food vacuoles. It has been demonstrated in cell-free medium that the incorporation of FP into ß-hematin under physiological conditions requires a catalyst from parasite lysates or pre-formed ß-hematin. In the present studies, lysates of Plasmodium falciparum-infected erythrocytes were suspended in 1 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°C, a large quantity of ß-hematin was formed. To determine whether parasite components were necessary for the ß-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 ß-hematin. Membranes treated with HCl or CH₃COOH also promoted the formation of ß-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 ß-hematin formation is discussed in this paper.

Key Words: hematin • ß-hematin • synthesis • activated membranes • catalyst

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