Transferrin and cellular iron exchange.

The importance of transferrin and iron for cell growth is well illustrated by the observation that proliferating cells in vitro have an absolute requirement for transferrin [l]. Although transferrin binds iron with a very high association constant (lo2' 121) cells are able to remove the iron and incorporate it into functional and storage compounds without degradation of the carrier protein. After removal of the iron, transferrin is released from cells and its unoccupied iron-binding sites become available to bind iron. Most of this comes from erythrocytes destroyed in the reticuloendothelial system. Smaller amounts of iron are released into the plasma by the gut mucosa, after absorption of food iron, and by the liver, where a depot of iron exists. Some of the cellular aspects of this cycle of iron exchange with transferrin have been studied using erythroid cells and in particular the reticulocyte. More recently, with the advent of techniques for the isolation and culture of non-erythroid mammalian cells it is becoming apparent that many of the underlying mechanisms in iron exchange are common to all cells. To utilize transferrin iron cells must express a plasma membrane receptor for the protein which allows the binding and uptake of transferrin and its passenger iron. The physical and chemical properties of this receptor, isolated from a variety of cells and tissues, have been studied.