Transferrins

Transferrins are iron-binding glycoproteins that transport iron through plasma and body fluids of vertebrates. In humans the principal serum transferrin, serotransferrin, is produced mainly by the liver and circulates in blood, binding about two iron atoms per molecule to keep iron soluble and bioavailable for cells that need it, notably erythroid precursors.

Each transferrin molecule has two iron-binding lobes; iron binding induces a closed conformation and high affinity. Binding requires a carbonate ion as a synergistic cofactor; iron is released in the acidified environment of endosomes after receptor-mediated uptake.

Transferrin transports iron by binding to transferrin receptors on cell surfaces (TfR1 and TfR2). The transferrin–iron–receptor complex is internalized by endocytosis; acidification triggers iron release to the cytosol, while apo-transferrin recycles to the surface and returns to circulation to pick up more iron.

Beyond serum transferrin, related transferrin-family proteins occur in other species and secretions. Lactoferrin and ovotransferrin are close relatives with iron-binding capacity and additional antimicrobial properties in milk, egg white, and other secretions.

Physiological and clinical aspects: Transferrin is a major regulator of iron homeostasis, acting in concert with ferritin and the hepcidin pathway. Transferrin levels rise in iron deficiency and fall during inflammation. Clinically, transferrin concentration, transferrin saturation (serum iron divided by total iron-binding capacity) and total iron-binding capacity are used to assess iron status. Abnormalities in transferrin–iron handling can contribute to iron-deficiency anemia or iron overload conditions.