Ferrous iron (Fe2+) in heme and labile iron pool (Fe2+)

Ferrous iron (Fe2+) serves as a critical pharmacological target in both its heme-bound form and within the labile iron pool (LIP), a transient, chelatable reservoir of redox-active iron in the cytosol (Source: PubMed, PMID: 11085924). In malaria treatment, the parasite's digestion of host hemoglobin releases heme, which contains Fe2+ that catalyzes the cleavage of the endoperoxide bridge in artemisinin-based drugs, generating lethal carbon-centered radicals (Source: Nature, doi:10.1038/nature16468). This activation is specific to the parasite's environment, where iron concentrations are high. The LIP also plays a central role in ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, making it a target for cancer therapy and neurodegenerative disease research (Source: Cell, doi:10.1016/j.cell.2012.03.042). Iron chelators like deferoxamine target the LIP to treat systemic iron overload and prevent oxidative damage mediated by the Fenton reaction (Source: StatPearls, NBK544256). These chelators bind Fe2+ or Fe3+ to facilitate excretion and reduce the pool of iron available for harmful radical generation. Consequently, managing the availability and redox state of Fe2+ is essential for controlling cellular toxicity and pathogen survival.

Other names

Ferrous ironLabile iron poolLIPHeme-bound ironFe(II)Intracellular iron pool

Artemisinin-based compounds are activated by the Fe2+ center in heme or the labile iron pool, leading to the formation of reactive oxygen species (ROS) and free radicals that alkylate essential parasite proteins (Source: PubMed, PMID: 16126454). Conversely, iron chelators bind to the labile iron pool to neutralize its redox activity and facilitate its excretion, thereby preventing iron-mediated tissue injury (Source: NIH, PubChem).