Haemozoin formation pathway (HFP) (HFP)

The haemozoin formation pathway is a critical detoxification process occurring within the acidic digestive vacuole of Plasmodium falciparum during its intraerythrocytic stage (Coronado et al., 2014). As the parasite digests host hemoglobin to obtain essential amino acids, it releases free heme (ferriprotoporphyrin IX), which is highly toxic due to its ability to generate reactive oxygen species and disrupt membrane integrity (Egan, 2008). To survive, the parasite converts this toxic heme into an insoluble, chemically inert crystalline form known as haemozoin, or malaria pigment (Coronado et al., 2014; Hempelmann, 2007). This biocrystallization process is the primary target for several classes of antimalarial drugs, most notably the quinolines like chloroquine and quinine (Sullivan et al., 1996). These drugs interfere with the pathway by binding to heme monomers or the growing faces of haemozoin crystals, preventing further polymerization and leading to the accumulation of toxic free heme, which ultimately kills the parasite (Egan, 2008; Sullivan et al., 1996). While primarily a non-enzymatic process, it is facilitated by the acidic environment and potentially by Heme Detoxification Protein (HDP) (Jani et al., 2008). Understanding this pathway is vital for developing new treatments, especially as resistance to traditional quinoline drugs continues to spread globally (Hempelmann, 2007).

Other names

Heme detoxification pathwayHeme biocrystallizationMalaria pigment formationβ-hematin formationHeme polymerization pathway

Inhibition of heme polymerization into haemozoin crystals, formation of toxic drug-heme complexes, and capping of crystal growth faces.