Physiological iron pool (LIP)

The physiological iron pool, scientifically referred to as the labile iron pool (LIP), is a dynamic and chemically reactive reservoir of intracellular iron that is not sequestered within storage proteins like ferritin or functional proteins like heme (Kakhlon & Cabantchik, 2002, PMID: 12421643). This pool consists of iron in both ferrous (Fe2+) and ferric (Fe3+) states, complexed with low-molecular-weight ligands such as citrate, acetate, or amino acids, making it readily available for essential metabolic processes including DNA replication and mitochondrial respiration (Halliwell & Gutteridge, 2015). Because this iron is redox-active, its concentration is strictly regulated; an expansion of the pool can catalyze the production of highly reactive hydroxyl radicals through the Fenton reaction, leading to lipid peroxidation and a form of regulated cell death known as ferroptosis (Dixon et al., 2012, PMID: 22624694). In pathological conditions such as hereditary hemochromatosis or transfusion-dependent thalassemia, the LIP becomes pathologically enlarged, necessitating the use of iron chelators like deferoxamine or deferasirox to prevent organ damage (StatPearls, 2023). Conversely, in iron-deficiency anemia, the pool is depleted, and therapeutic intervention involves iron supplementation to restore the physiological levels required for healthy erythropoiesis (NIH, 2023). Monitoring this pool is critical in clinical settings, as it serves as a direct indicator of potential oxidative risk and therapeutic efficacy in iron-related disorders.

Other names

Labile iron poolChelatable iron poolNon-protein-bound ironFree iron poolIntracellular labile iron

Iron chelators bind to the redox-active ions within the labile iron pool to form stable, non-toxic complexes that are subsequently excreted, thereby preventing the generation of reactive oxygen species via the Fenton reaction. In contrast, iron supplements provide exogenous iron to replenish this pool, ensuring sufficient availability for erythropoiesis and enzymatic functions.