A model for regulation of dietary iron absorption by transferrin (Tf) and macrophages in the duodenum. The presence of apo-Tf allows the efflux from enterocytes via ferroportin (FPN1) and the ferroxidase hephaestin (Heph), which oxidizes Fe2⁺ to Fe3⁺ to allow scavenging on Tf (left panel). When more apo-Tf is available, for example by injection of apo-Tf, a higher iron efflux through FPN1 is stimulated by providing more acceptor molecules, shifting the equilibrium (middle panel). Macrophages in the lamina propria can degrade Tf via the action of proteases and thereby reduce iron efflux from enterocytes (right panel).