MALARIAL HAEMOZOIN BETA-HEMATIN SUPPORTS HEME POLYMERIZATION IN THE ABSENCE OF PROTEIN

MALARIAL parasites growing inside erythrocytes digest up to 80% of the host cell's haemoglobin within a lysosomal organelle, the digestive v acuole(1,2). They sequester the potentially toxic haem (Fe (II) protoh aematoporphyrin) that is released during this process into an insolubl e pigment called haemozoin, which consists of polymerized Fe(III) prot ohaematoporphyrin subunits(3). We have studied this process of haem po lymerization, which was previously reported to be enzyme-mediated and the target of the quinoline antimalarial drugs chloroquine and quinine (4). Here we show that, rather than being enzyme-mediated, haem polyme rization is actually a chemical process, dependent only on the presenc e of haem-derived material associated with haemozoin and not on protei n. This discovery does not invalidate haem polymerization as a target for drug intervention and the mechanism by which haemozoin formation i s initiated is still not understood, but our view of this process and of the action of chloroquine must be reconsidered.