Plasmodium falciparum ferriprotoporphyrin IX (FP-IX)

Plasmodium falciparum ferriprotoporphyrin IX (heme) is a toxic metabolic byproduct generated during the intraerythrocytic stage of the malaria parasite's life cycle. As the parasite digests host hemoglobin within its acidic food vacuole to obtain essential amino acids, it releases large quantities of free heme, which can disrupt lipid membranes and generate reactive oxygen species (Source: PubMed, PMID: 11586530). To survive, the parasite detoxifies this molecule by polymerizing it into an insoluble, chemically inert crystalline form known as hemozoin, or malaria pigment (Source: Journal of Inorganic Biochemistry, DOI: 10.1016/j.jinorgbio.2008.06.007). This detoxification pathway is the primary target for several classes of antimalarial drugs, most notably the quinolines like chloroquine and quinine. These drugs bind to heme monomers or the growing faces of hemozoin crystals, preventing further polymerization and leading to the lethal accumulation of free heme or drug-heme complexes within the parasite (Source: Nature Communications, DOI: 10.1038/ncomms11551). Additionally, artemisinin-based compounds are thought to be activated by the iron in heme, leading to the formation of free radicals that damage parasite proteins and lipids (Source: NIH/NIAID).

Other names

HemeHematinFerriprotoporphyrin IXMalaria pigment precursorFree heme

Inhibition of hemozoin biocrystallization and induction of heme-mediated oxidative toxicity.