Iron(III)-protoporphyrin IX (Fe(III)PPIX)

Iron(III)-protoporphyrin IX, commonly referred to as heme or ferriprotoporphyrin IX, is a toxic byproduct generated during the intraerythrocytic stage of the Plasmodium falciparum life cycle (Fitch et al., 1984). As the parasite digests host hemoglobin within its acidic food vacuole to obtain essential amino acids, it releases large quantities of free heme. Because free heme is highly toxic—inducing oxidative stress, lipid peroxidation, and membrane damage—the parasite must detoxify it by sequestering it into an insoluble crystalline form called hemozoin, or malaria pigment (Egan, 2008). This detoxification process is a critical vulnerability and serves as the primary target for several classes of antimalarial drugs, most notably the quinolines (Sullivan et al., 1998). Drugs like chloroquine bind to Fe(III)PPIX, preventing its incorporation into hemozoin and resulting in the accumulation of toxic heme-drug complexes that ultimately kill the parasite (Sigala et al., 2015).

Other names

HemeFerriprotoporphyrin IXHematinHeminMalaria pigment precursor

Inhibition of heme biocrystallization (hemozoin formation), leading to the accumulation of toxic free heme and oxidative damage to the parasite.