Heme detoxification protein (HDP) (HDP)

Heme detoxification protein (HDP) is a critical factor in the survival of Plasmodium parasites, the causative agents of malaria (Jani et al., 2008). During the intraerythrocytic stage, the parasite digests host hemoglobin, releasing large quantities of free heme (ferriprotoporphyrin IX), which is highly toxic due to its ability to destabilize membranes and produce reactive oxygen species (Coronado et al., 2014). To neutralize this threat, the parasite utilizes HDP to rapidly catalyze the crystallization of free heme into an insoluble, non-toxic crystalline pigment known as hemozoin or β-hematin (Sullivan, 2002). This detoxification pathway is a primary target for several classes of antimalarial drugs, most notably the 4-aminoquinolines like chloroquine, which interfere with the crystallization process (Pagola et al., 2000). By preventing hemozoin formation, these drugs cause toxic heme to accumulate within the parasite's digestive vacuole, ultimately leading to parasite death (Egan, 2008). Consequently, HDP and the crystallization process represent a cornerstone of antimalarial pharmacology and a focus for overcoming drug resistance (Chugh et al., 2013).

Other names

Plasmodium falciparum heme detoxification proteinPfHDPHeme crystallization pathwayHemozoin synthaseβ-hematin crystallization

Inhibition of heme crystallization into hemozoin, leading to the accumulation of toxic free heme (ferriprotoporphyrin IX) which causes parasite death through oxidative damage and membrane disruption.