Synthetic chelating agents in iron metabolism.

Iron in man is held within the cells incorporated in organic complex molecules, either as functional iron, i.e., hemoglobin and tissue enzymes, or as storage iron, i.e., ferritin and hemosiderin. Owing to the requirements of the erythroid marrow in particular, large amounts of iron must constantly pass from one cell to another through the plasma. This plasma transport is brought about by a #3globulin transferrin, which handles iron in a highly selective fashion, removing it from donor tissues such as the reticuloendothelial cells and releasing it to those tissues which have a need for iron. It is likely that this direction of motion is accomplished by the relative affinity of individual cellular receptors for iron as compared to that of transferrin. Thus weaker receptors yield iron to transferrin and stronger receptors assimilate it. Recently, powerful chelating agents have been developed which may participate in tissue iron exchange (1-10). Such chelates have been shown to compete in vitro with transferrin for iron (5, 6). They have also been shown to mobilize iron from body tissues when injected parenterally (3, 4). It is the aim of the present study to investigate the effects of this competitive binding of chelates in reactions of iron transport. The observations made further define the mode of action of these compounds on intermediate iron metabolism and indicate their usefulness in the treatment of acute or chronic iron overload.