Depolymerization of malarial hemozoin: a novel reaction initiated by blood schizontocidal antimalarials.
Malaria parasite digests hemoglobin and utilizes the globin part for its nutritional requirements. Heme released as a byproduct of hemoglobin degradation is detoxified by polymerization into a crystalline, insoluble pigment, known as hemozoin. We have identified a novel reaction of depolymerization of hemozoin to heme. This reaction is initiated by the interaction of blood schizonticidal antimalarial drugs with the malarial hemozoin. The reaction has been confirmed, with the purified hemozoin as well as the lysate of the malaria parasite. Pigment breakdown was studied by infrared spectroscopy, thin-layer chromatography and spectrophotometric analysis. It was complete within 2 h of drug exposure, which explains the selective sensitivity of late stages (trophozoites and schizonts) of malarial parasites loaded with the hemozoin pigment to the toxic action of these drugs. It is suggested that the failure of the parasite heme detoxification system due to this reaction results in the accumulation of toxic heme, which alone, or complexed with the antimalarial leads to the death of malaria parasite.
Pandey
A V
AV
Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
Tekwani
B L
BL
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D006418:Heme / Q000378:metabolism; D006420:Hemeproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D007700:Kinetics; D008288:Malaria / Q000097:blood; D051379:Mice; D008954:Models, Biological; D010860:Pigments, Biological / Q000737:chemistry / Q000378:metabolism*; D010967:Plasmodium yoelii / Q000378:metabolism*
D000962:Antimalarials; D006420:Hemeproteins; D006454:Hemoglobins; D010860:Pigments, Biological; C020753:hemozoin; D006418:Heme; D002738:Chloroquine