The incidence of human
malaria has increased during the past 20 years; 270 million people are now estimated to be infected with the parasite. An important contribution to this increase has been the appearance of
malaria organisms resistant to
quinoline-containing
antimalarials such as
chloroquine and
quinine. These drugs accumulate in the
acid food vacuoles of the intraerythrocytic-stage
malaria parasite, although the mechanism of their specific toxicity in this organelle is uncertain. The primary function of the food vacuole is the proteolysis of ingested red cell haemoglobin to provide the growing parasite with
essential amino acids. Haemoglobin breakdown in the food vacuole releases
haem, which if soluble can damage
biological membranes and inhibit a variety of
enzymes. Rather than degrading or excreting the
haem, the parasite has evolved a novel pathway for its detoxification by incorporating it into an insoluble crystalline material called
haemozoin or
malaria pigment. These crystals form in the food vacuole of the parasite concomitant with haemoglobin degradation, where they remain until the infected red cell bursts. The structure of
haemozoin comprises a
polymer of haems linked between the central ferric ion of one
haem and a carboxylate side-group
oxygen of another. This structure does not form spontaneously from either free
haem or haemoglobin under physiological conditions, and the biochemistry of its formation is unclear. Here we report the identification and characterization of a
haem polymerase enzyme activity from extracts of Plasmodium falciparum trophozoites, and show that this
enzyme is inhibited by
quinoline-containing drugs such as
chloroquine and
quinine. This provides a possible explanation for the highly stage-specific
antimalarial properties of these drugs.