Plasmodium heme polymerase (HDP)

Plasmodium heme polymerase refers to the biological activity or protein complex, specifically the Heme Detoxification Protein (HDP), that facilitates the conversion of toxic free heme into inert hemozoin crystals [Jani et al., 2008, PLoS Pathogens]. This process occurs within the acidic digestive vacuole of the malaria parasite during the intraerythrocytic stage, where the parasite digests host hemoglobin to obtain essential amino acids [Slater & Cerami, 1992, Nature]. The digestion releases ferriprotoporphyrin IX (free heme), which is highly toxic to the parasite as it generates reactive oxygen species and disrupts cellular membranes [Huy et al., 2013, Curr Med Chem]. To survive, the parasite utilizes the heme polymerase activity to sequester heme into chemically inert hemozoin, also known as malaria pigment. This pathway is the primary therapeutic target for 4-aminoquinoline drugs such as amodiaquine and chloroquine [PubChem CID 2165]. Amodiaquine binds to heme monomers or the growing faces of hemozoin crystals, effectively inhibiting further polymerization and leading to the accumulation of toxic heme, which results in parasite death [StatPearls, Malaria].

Other names

Heme detoxification proteinHDPHeme biocrystallization catalystHemozoin synthaseFerriprotoporphyrin IX polymerase

Inhibition of heme biocrystallization into hemozoin, leading to the accumulation of toxic free heme and subsequent oxidative damage to the parasite.