Heme (protoporphyrin IX) (Heme or heme PPIX)

Heme (protoporphyrin IX) is a small, iron-containing molecule released in large amounts when Plasmodium falciparum digest host hemoglobin inside infected red blood cells. Free heme is highly toxic to the parasite due to its pro-oxidative properties. To survive, P. falciparum polymerizes heme into an insoluble and inert crystal called hemozoin within its digestive vacuole—a process essential for parasite viability. This detoxification process, not heme itself, is the target of many antimalarial drugs, which act by interfering with heme polymerization and thereby increasing the toxic free heme concentration, ultimately killing the parasite. Heme itself is not a direct therapeutic target protein or receptor, but rather a process substrate and drug focus point.

Other names

Ferriprotoporphyrin IXFe(III)-protoporphyrin IXhematinheme PPIX

Drugs interact with heme by: preventing its crystallization into inert hemozoin; complexing with heme to inhibit detoxification and elevate toxic free heme within the parasite, leading to death. This includes inhibition of hemozoin formation, heme complexation, and increase in toxic free heme.