Figure 1.

The process of Tf binding to a receptor to transport iron. The iron (Fe³⁺⁾ in food is reduced to “Fe²⁺ ”under the action of gastric acid and reducing substances, which is absorbed by intestinal mucosa cells, the absorbed “Fe²⁺ ” is oxidized as “Fe³⁺ by ceruloplasmin, then Fe³⁺ binds to Tf, and the conformation of Tf changes immediately after binding with Fe³⁺, which helps Tf to bind to the Tf receptor (TfR) on the cell membrane surface to form a “TfR-Tf-Fe³⁺” complex. Subsequently, the complex enters the cell through receptor-mediated endocytosis to form an endosome coated with clathrin. In the acidic milieu (pH<5.5) in the endosome, Fe³⁺ dissociates from Tf and is reduced to Fe²⁺ by metalloreductases such as six-transmembrane epithelial antigen of the prostate 3 (STEAP3) followed by transportation into the cytosol by divalent metal transporter 1 (DMT1).Following, the Tf/TfR complex recirculates to the cell surface, separates, and enters into the blood circulation for the next process of iron ion transport.

Abbreviations: Apo-Tf, non-iron bound transferrin; Holo-Tf, diferric transferrin; TfR, Tf receptor; STEAP3, six-transmembrane epithelial antigen of the prostate 3; DMT1, divalent metal transporter 1.