Ferriprotoporphyrin IX (Fe(III)PPIX) (Fe(III)PPIX)

Ferriprotoporphyrin IX (heme) is a vital metabolic byproduct and therapeutic target located within the acidic food vacuole of the malaria parasite Plasmodium falciparum (Sigala & Goldberg, 2014). During the parasite's intraerythrocytic stage, it digests host hemoglobin to obtain amino acids, a process that releases toxic, redox-active free heme (Sullivan, 2002). To prevent cellular damage, the parasite detoxifies this heme by sequestering it into an insoluble crystalline polymer called hemozoin (Egan, 2008). Antimalarial drugs, most notably the 4-aminoquinolines like chloroquine, target this pathway by binding to the heme monomers or the growing faces of hemozoin crystals (Hempelmann, 2007). This binding inhibits further crystallization, leading to an accumulation of toxic heme-drug complexes that cause membrane lipid peroxidation and parasite death (Coronado et al., 2014). Consequently, the disruption of heme detoxification remains one of the most successful strategies in antimalarial chemotherapy.

Other names

HemeHematinFree hemeProtoporphyrin IX iron(III) complexMalaria pigment precursor

Inhibition of hemozoin biocrystallization and formation of toxic heme-drug complexes.