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Plasmodium falciparum heme, specifically ferriprotoporphyrin IX (Fe(III)PPIX), is a toxic byproduct generated during the digestion of host hemoglobin within the parasite's acidic food vacuole (Egan, 2008). Because free heme is redox-active and can cause extensive membrane damage and oxidative stress, the parasite must detoxify it by sequestering it into chemically inert crystals known as hemozoin or malaria pigment (Sullivan, 2002). This detoxification process is a critical vulnerability in the parasite's life cycle and serves as the primary target for several classes of antimalarial drugs (Hempelmann, 2007). Quinolines, such as chloroquine and quinine, bind to heme or the surface of growing hemozoin crystals to prevent further polymerization, resulting in the accumulation of toxic heme that kills the parasite (Egan, 2008). Additionally, artemisinin-based compounds are activated by heme, leading to the production of free radicals that damage parasite proteins and lipids (Tilley et al., 2016).
Inhibition of heme biocrystallization into hemozoin and formation of toxic drug-heme complexes (Egan, 2008; Sullivan, 2002).
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