The biology of transferrin

The chemistry and molecular biology of transferrin is discussed. The discussion covers the genetic control of transferrin synthesis, its intracellular synthesis, intra- and extracellular transport, and its interaction with transferrin receptors. The role of transferrin in iron metabolism is evaluated, both with regard to iron uptake by transferrin as to iron uptake from transferrin by different cells. The knowledge on the biochemical mechanisms involved in iron uptake is presented, with special reference to the triple role of the acidification of endocytotic vesicles. Apart from its traditional role in iron metabolism, transferrin acts as a growth factor. A distinction of two groups of growth-stimulating properties of transferrin has been made. As an early effect, membranous and intracellular changes are initiated, possibly based on electrochemical effects on the cell. The late effects seem to relate to its role in iron transport. Interestingly, the early growth stimulating effects can be segregated from the former function of transferrin and strictly speaking neither depend on iron nor on the transferrin molecule itself. Also the trophic effect of transferrin on several cell types has been described. Hypotheses concerning the biochemical basis of this effect are presented and within this context a new hypothesis on the differential occupation of iron binding sites of serum transferrin is forwarded. Examples of the applicability of present understanding of the biology of transferrin in clinical settings are presented.