Transfer of iron from serum iron-binding protein to human reticulocytes.

The metabolism of iron involves a series of compounds which restrict iron to undissociated forms. Upon absorption by gut mucosal cells, iron is enveloped within ferritin molecules (1, 2). In the presence of reducing agents, ferritin iron then is released to the surfaces of ferritin molecules (3) to become bound by a specialized transport protein of the plasma.' This iron-binding protein (IBP) is a ,81 globulin by electrophoretic analysis but resembles albumin in chemical properties (5, 8). Each molecule of IBP from human plasma or from the plasma of several other mammalian species studied, in common with the IBP of egg white, "conalbumin," binds two iron atoms to form a colored complex (5, 9-12). Iron bound by these proteins is in the ferric state (5, 8) and is tightly chelated in complexes which apparently contain three phenolic groups and one bicarbonate ion (7, 11, 12). At a physiologic pH and bicarbonate concentration the iron-IBP complex is extremely stable. In some manner, however, iron is transferred from IBP to immature red cells for incorporation into heme. Although it is well established that immature red cells, either as intact cells or as hemolysates, can utilize ionic iron for heme synthesis (13-20), little is known of the mechanism releasing iron from plasma IBP for cellular utilization. It is often assumed that this mechanism for transfer-