Heme and Plasmodium falciparum proteins

Heme and multiple Plasmodium falciparum proteins constitute a complex target system central to the pharmacology of antimalarial drugs, particularly the artemisinin family (Wang et al., 2015). In the malaria parasite's life cycle, host hemoglobin is digested within the food vacuole, releasing toxic free heme, also known as ferriprotoporphyrin IX (Sullivan, 2002). Artemisinin and its derivatives are activated by the iron in this heme, leading to the cleavage of their endoperoxide bridge and the generation of highly reactive carbon-centered radicals (O’Neill et al., 2010). These radicals then perform promiscuous alkylation, binding to and inactivating a wide array of essential Plasmodium falciparum proteins involved in various metabolic pathways (Tilley et al., 2016). This multi-target mechanism explains the rapid and potent action of artemisinins against various stages of the parasite. Additionally, other drugs like chloroquine interact with heme to prevent its detoxification into inert hemozoin crystals, leading to heme-mediated toxicity (PubMed, 2023). Understanding this interaction is critical for addressing emerging drug resistance, often mediated by mutations in the Kelch 13 (K13) protein (Ariey et al., 2014).

Other names

Ferriprotoporphyrin IXHemozoin precursorsPlasmodium falciparum proteomeMalaria pigment precursors

Activation by heme to generate reactive radicals that alkylate multiple parasite proteins; inhibition of heme polymerization into hemozoin.