Heme in Plasmodium falciparum digestive vacuole

Heme in the digestive vacuole of Plasmodium falciparum is a prosthetic group (iron protoporphyrin IX) that is liberated as a toxic byproduct during the digestion of hemoglobin by the malaria parasite. Within the acidic digestive vacuole, Plasmodium falciparum rapidly detoxifies heme by polymerizing it into the inert crystalline pigment hemozoin. Failure to detoxify heme is lethal to the parasite. Multiple antimalarial drugs, such as chloroquine and related quinolines, exert their effect by interfering with the polymerization of heme, thereby causing accumulation of toxic free heme and death of the parasite[1][3][4][5][6]. Artemisinin is activated by heme and induces oxidative damage. Heme itself is not a protein or receptor, but a small molecule 'co-target' critical for antimalarial drug action in the digestive vacuole. While it is not a traditional druggable target (enzyme, receptor, transporter), it serves as an essential intermediate that is therapeutically exploited in antimalarial drug design. Note on correctness: There is something incorrect about this target as stated: "Heme in Plasmodium falciparum digestive vacuole" is not a canonical target name, receptor, or protein, but rather a small molecule intermediate generated and detoxified as a byproduct of hemoglobin digestion. The real molecular target for many antimalarials is the process of heme detoxification (hemozoin formation), or other proteins in the digestive vacuole (such as Plasmodium falciparum chloroquine resistance transporter or the hemozoin-synthesizing protein HRP II)[1][6]. Thus, this is not a protein or classic receptor but is often considered a 'biochemical target' for antimalarial drug mechanism studies.

Other names

Heme in Plasmodium falciparum food vacuoleFerriprotoporphyrin IX in Plasmodium digestive vacuoleFerriheme in Plasmodium digestive vacuoleHematin in Plasmodium digestive vacuole

Inhibition of heme detoxification via binding to free heme Prevention of hemozoin (malaria pigment) crystallization Generation of reactive oxygen species mediated by heme in the presence of drugs (for example, artemisinin activation)[3][6]