Bioavailable iron and heme metabolism in Plasmodium falciparum.
Iron metabolism is essential for cell function and potentially toxic because iron can catalyze oxygen radical production. Malaria-attributable anemia and iron deficiency anemia coincide as being treatable diseases in the developing world. In absolute amounts, more than 95% of Plasmodium metal biochemistry occurs in the acidic digestive vacuole where heme released from hemoglobin catabolism forms heme crystals. The antimalarial quinolines interfere with crystallization. Despite the completion of the Plasmodium genome, many 'gene gaps' exist in components of the metal pathways described in mammalian or yeast cells. Present evidence suggests that parasite bioavailable iron originates from a labile erythrocyte cytosolic pool rather than from abundant heme iron. Indeed the parasite has to make its own heme within two separate organelles, the mitochondrion and the apicomplast. Paradoxically, despite the abundance of iron within the erythrocyte, iron chelators are cytocidal to the Plasmodium parasite. Hemozoin has become a sensitive biomarker for laser desorption mass spectrometry detection of Plasmodium infection in both mice and humans.
Scholl
P F
PF
Department of Environmental Health Sciences, Baltimore, MD 21205, USA.
Tripathi
A K
AK
Sullivan
D J
DJ
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D006418:Heme / Q000378:metabolism*; D006420:Hemeproteins / Q000032:analysis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000469:parasitology; D051379:Mice; D010963:Plasmodium falciparum / Q000378:metabolism*
D000962:Antimalarials; D002614:Chelating Agents; D006420:Hemeproteins; C020753:hemozoin; D006418:Heme; D007501:Iron