Labile iron pool and non-transferrin-bound iron (LIP and NTBI)

The labile iron pool (LIP) and non-transferrin-bound iron (NTBI) represent the chemically reactive, chelatable fractions of iron found within cells and in the systemic circulation, respectively (Kakhlon & Cabantchik, 2002). Under physiological conditions, iron is safely sequestered by proteins like transferrin and ferritin; however, in states of iron overload or metabolic dysfunction, these labile pools expand significantly (Breuer et al., 2000). Labile iron consists of both ferrous (Fe2+) and ferric (Fe3+) ions associated with low-molecular-weight ligands, making them highly prone to participating in Fenton and Haber-Weiss reactions. These reactions generate hydroxyl radicals and other reactive oxygen species (ROS), leading to lipid peroxidation, protein damage, and DNA mutations (Halliwell & Gutteridge, 2015). Clinically, these pools are the primary targets for iron chelation therapy in diseases such as thalassemia and hemochromatosis to prevent organ damage in the heart, liver, and endocrine glands. Furthermore, the LIP is a critical regulator of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation (Dixon et al., 2012). Drugs like Deferoxamine and Deferasirox work by binding these ions with high affinity to neutralize their redox activity and facilitate their excretion (Kontoghiorghes, 2020).

Other names

LIPNTBILabile plasma ironLPIChelatable iron poolRedox-active ironFree iron

Chelation of Fe2+ and Fe3+ ions to form stable, non-toxic complexes that are subsequently excreted from the body via the kidneys or bile, thereby preventing the formation of reactive oxygen species through Fenton chemistry.