Heme (Iron-protoporphyrin IX) and heme-dependent proteins (Heme/Fe(III)-PPIX)

Heme (Iron-protoporphyrin IX) is a central molecule in the pathogenesis of Plasmodium falciparum malaria. During its intraerythrocytic stage, the parasite digests up to 80% of host hemoglobin to acquire essential amino acids, a process that releases toxic free heme (Ferriprotoporphyrin IX) (Francis et al., 1997, Annu Rev Microbiol). To prevent oxidative damage and membrane lysis, the parasite detoxifies heme by sequestering it into an inert crystalline polymer called hemozoin, or malaria pigment (Egan, 2008, J Inorg Biochem). This biocrystallization pathway is the primary target of quinoline-based antimalarials like chloroquine, which bind to heme and prevent its incorporation into hemozoin, resulting in parasite death due to heme toxicity (Sullivan et al., 1996, Science). Furthermore, heme acts as a crucial activator for artemisinin-based drugs; the iron in heme facilitates the cleavage of the drug's endoperoxide bridge, generating carbon-centered radicals that alkylate various parasite proteins (Meshnick, 2002, Int J Parasitol). Beyond detoxification, heme-dependent proteins such as Cytochrome b in the mitochondrial electron transport chain are also vital targets, specifically for drugs like atovaquone (Kessl et al., 2003, J Biol Chem). The target name provided in the prompt contained a typographical error (a closing parenthesis) and combined a molecule with a functional class of proteins.

Other names

Ferriprotoporphyrin IXFP-IXHematinHemozoin precursorIron-protoporphyrin IXMalaria pigment precursor

Inhibition of hemozoin biocrystallization (Egan, 2008, J Inorg Biochem), formation of toxic heme-drug complexes (Sullivan et al., 1996, Science), and heme-mediated activation of endoperoxide prodrugs to generate lethal free radicals (Meshnick, 2002, Int J Parasitol).