Parasitic heme metabolism proteins

Parasitic proteins involved in heme metabolism represent a vital class of therapeutic targets, particularly in blood-feeding parasites such as Plasmodium falciparum and Schistosoma (Sigala and Goldberg, 2014; J. Drug Target, 2019). These organisms must balance the acquisition of heme for essential functions, such as mitochondrial respiration, with the detoxification of the massive quantities of free heme released during the digestion of host hemoglobin (PLOS Pathogens, 2013; Jani et al., 2008). The primary detoxification strategy is the biomineralization of toxic heme into inert hemozoin crystals, a process mediated by the Heme Detoxification Protein (HDP) and Histidine-Rich Proteins (HRPs) (Jani et al., 2008; NIH, 2013). Traditional antimalarial drugs like chloroquine and other quinolines function by binding to heme and preventing its sequestration into hemozoin, thereby causing the accumulation of toxic free heme within the parasite (ASM, 2021; NIH, 2001). Modern artemisinin-based therapies are activated by heme to generate reactive oxygen species and carbon-centered radicals that alkylate and damage parasite proteins (ResearchGate, 2021; ASM, 2021). Furthermore, the unique and compartmentalized heme biosynthesis pathway found in some parasites offers additional targets, such as the use of 5-aminolevulinic acid (ALA) to induce the accumulation of phototoxic porphyrins in a bait-and-kill approach (Sigala and Goldberg, 2014; NIH, 2026).

Other names

Heme detoxification pathwayHemozoin formation pathwayParasitic heme biosynthesis and degradation proteinsHeme metabolism in parasites

Inhibition of hemozoin crystallization (biomineralization), activation of endoperoxides by heme to produce toxic radicals, and inhibition of heme biosynthesis enzymes.