title: Heme polymerase: modulation by chloroquine treatment of a rodent malaria.
abstract: The biosynthesis of the beta-hematin of malarial pigment (hemozoin) is catalyzed by a newly discovered enzyme, heme polymerase, which is described for Plasmodium berghei in this report. This novel enzyme is present in the insoluble fraction of hemolysates of infected erythrocytes but is not present in normal erythrocytes. The substrate is ferriprotoporphyrin IX (FP) released from hemoglobin. At pH 5 and 37 degrees C the enzyme is saturated by 100 microM FP. The pH optimum is between 5 and 6 and the reaction is linear for 6 hours. All heme polymerase activity is destroyed by heating at 100 degrees C for 3 minutes. Chloroquine treatment of malarious mice reduces by 80 percent the activity of this enzyme, without inhibiting release of FP from hemoglobin, and thereby causes excess nonpolymerized, nonhemozoin FP to accumulate. Since the accumulated FP is accessible to bind chloroquine, we propose that it is the mediator of the antimalarial activity of chloroquine.
authors: Department of Internal Medicine, Saint Louis University School of Medicine, Missouri 63104.
authors: A C
authors: AC
authors: Chou
authors: C D
authors: CD
authors: Fitch
mesh_terms: D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004795:Enzyme Stability; D004912:Erythrocytes / Q000201:enzymology / Q000469:parasitology; D006427:Hemin / Q000096:biosynthesis / Q000378:metabolism; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D008288:Malaria / Q000188:drug therapy / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D051379:Mice; D010962:Plasmodium berghei / Q000201:enzymology* / Q000254:growth & development; D013379:Substrate Specificity; D014166:Transferases / Q000378:metabolism*
chemical_list: D006427:Hemin; D002738:Chloroquine; D014166:Transferases; C072176:heme polymerase