Plasmodium heme detoxification pathway (HDP) (HDP)

The Plasmodium heme detoxification pathway is a vital metabolic process used by malaria parasites to survive within host erythrocytes [Jani et al., 2008, PLoS Pathogens]. During the intraerythrocytic stage, the parasite digests host hemoglobin to acquire essential amino acids, a process that releases large amounts of free heme (ferriprotoporphyrin IX) [Coronado et al., 2014, Frontiers in Pharmacology]. Free heme is highly toxic to the parasite as it induces oxidative stress and damages lipid membranes [Sullivan, 2002, Int J Parasitol]. To neutralize this threat, the parasite converts free heme into an insoluble, chemically inert crystalline polymer called hemozoin, or malaria pigment [Huy et al., 2002, J Biochem]. This biocrystallization is primarily mediated by the Heme Detoxification Protein (HDP), which was historically referred to as heme polymerase [Jani et al., 2008]. Quinolone-based antimalarial drugs, including chloroquine and quinine, target this pathway by binding to heme monomers or the surface of growing hemozoin crystals [DrugBank DB00608]. This binding effectively halts the detoxification process, leading to the accumulation of toxic heme-drug complexes that cause parasite death [Coronado et al., 2014]. The pathway is a cornerstone of antimalarial therapy, though its efficacy is increasingly challenged by the evolution of resistance mechanisms in Plasmodium falciparum [Sullivan, 2002].

Other names

Heme polymeraseHemozoin formation pathwayHeme biocrystallizationFerriprotoporphyrin IX detoxification

Inhibition of heme biocrystallization into hemozoin, leading to the accumulation of toxic free ferriprotoporphyrin IX [DrugBank DB00608, Coronado et al., 2014].