HEME POLYMERASE-ACTIVITY AND THE STAGE SPECIFICITY OF ANTIMALARIAL ACTION OF CHLOROQUINE

Plasmodium falciparum lysate, prepared from 2.7 x 10(7) ring-infected erythrocytes and incubated with hemoglobin in sodium acetate at pH 5, incorporated a mean of 1.6 nmol of ferriprotoporphyrin IX (FP) into he mozoin in 18 to 22 hr. A similar preparation of trophozoite lysate inc orporated a mean of 3.6 nmol of FP into hemozoin in 4 to 6 hr. These f indings indicate differences between heme polymerase activity (hemozoi n production) at the ring and trophozoite stages of malaria parasites. Intracellular hemozoin production was 90% inhibited at the ring and t rophozoite stages by 0.5 and 7 nmol of chloroquine/10(6) infected eryt hrocytes. respectively. The inhibition killed the rings but not the tr ophozoites, suggesting that mature parasites may have a mechanism for protecting themselves against chloroquine-FP toxicity.