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Plasmodium falciparum Endoperoxide Activation Pathway (None)
- Target
- None
- Molecular classification
- Biochemical Pathway
01
Overview
The Plasmodium falciparum endoperoxide activation pathway is a crucial process by which artemisinin and related endoperoxide antimalarial drugs are activated. This activation occurs in the parasite's digestive vacuole, driven by Fe(II)PPIX (heme) released during hemoglobin digestion. The heme cleaves the drug's endoperoxide bridge, generating cytotoxic carbon-centered free radicals that damage parasite proteins and membranes, leading to parasite death. The effectiveness of artemisinin depends on this pathway, and resistance can arise if parasites alter hemoglobin digestion or reduce available Fe(II)PPIX.
- Other names
- Artemisinin activation pathwayEndoperoxide activation in PlasmodiumHeme-mediated artemisinin activation
02
Mechanism of action
Fe(II)PPIX-dependent cleavage of endoperoxide bond leading to generation of cytotoxic reactive intermediates, protein alkylation and downstream damage
03
Biological functions
Drug activationReactive oxygen species generationParasite killing
04
Disease associations
Malaria
05
Safety considerations
Artemisinin resistanceReduced heme availability
06
Interacting drugs
Artemisinin
3 more in the full profile.
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