title: Malarial haemozoin/beta-haematin supports haem polymerization in the absence of protein.
abstract: Malarial parasites growing inside erythrocytes digest up to 80% of the host cell's haemoglobin within a lysosomal organelle, the digestive vacuole. They sequester the potentially toxic haem (Fe (II) protohaematoporphyrin) that is released during this process into an insoluble pigment called haemozoin, which consists of polymerized Fe (III) protohaematoporphyrin subunits. We have studied this process of haem polymerization, which was previously reported to be enzyme-mediated and the target of the quinoline antimalarial drugs chloroquine and quinine. Here we show that, rather than being enzyme-mediated, haem polymerization is actually a chemical process, dependent only on the presence of haem-derived material associated with haemozoin and not on protein. This discovery does not invalidate haem polymerization as a target for drug intervention and the mechanism by which haemozoin formation is initiated is still not understood, but our view of this process and of the action of choroquine must be reconsidered.
authors.affiliation: Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Dorn
authors.forename: R
authors.initials: R
authors.lastname: Stoffel
authors.forename: H
authors.initials: H
authors.lastname: Matile
authors.forename: A
authors.initials: A
authors.lastname: Bubendorf
authors.forename: R G
authors.initials: RG
authors.lastname: Ridley
mesh_terms: D000818:Animals; D001704:Biopolymers; D006418:Heme / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism
chemical_list: D001704:Biopolymers; D006420:Hemeproteins; D011506:Proteins; C020753:hemozoin; D006418:Heme; D014166:Transferases; C072176:heme polymerase