irontransferrin

Irontransferrin, commonly referred to as holotransferrin, is the iron‑saturated form of the plasma transport protein transferrin. Transferrin is a ~80 kDa glycoprotein produced mainly by the liver and circulating in blood, where it binds and ferries ferric ions (Fe3+) to cells throughout the body. A single transferrin molecule has two high‑affinity iron‑binding sites and can carry up to two Fe3+ ions. The iron bound to transferrin is delivered to cells by interaction with transferrin receptors on the cell surface, particularly transferrin receptor 1 (TFRC).

Uptake begins when the transferrin–iron complex binds to its receptor and is internalized by receptor‑mediated endocytosis. Within the acidic endosome, a conformational change lowers transferrin’s affinity for iron, releasing Fe3+. The iron is then reduced to Fe2+ by ferrireductases and transported into the cytosol by DMT1 (divalent metal transporter 1) for use in processes such as heme synthesis and iron‑sulfur cluster assembly. The apotransferrin–receptor complex recycles back to the cell surface, where neutral pH promotes release of apotransferrin to rebind iron in circulation.

Physiologically, the level of iron saturation of transferrin reflects iron status and is influenced by regulation of iron absorption and storage, notably by the peptide hormone hepcidin. Disorders of irontransferrin balance contribute to iron deficiency anemia or iron overload conditions. Clinically, measurements of holo/transferrin saturation and related parameters help assess iron status and informing management.