Iron and protein kinetics studied by means of doubly labeled human crystalline transferrin.

Although proteins isotopically labeled with iodine have been used in tracer studies for some years, interest has been mainly focused on their distribution and degradation in the body. While it is often possible to produce iodoproteins whose physical and chemical properties are not grossly altered, the possible effects of iodination on the functional properties of such substances in a physiologic setting have been less thoroughly investigated. That it is possible to trace label proteins without significantly reducing their biological activities has been demonstrated in the case of insulin (2) and certain anterior pituitary hormones (3, 4). Transferrin (siderophilin, iron-binding globulin), a /3-globulin found in the plasma of man (5, 6) and other animal species (7, 8), is thought to function primarily as a transport vehicle for iron (9). It is remarkably similar in its metalbinding properties to conalbumin, an egg white pseudoglobulin, and, indeed, it has been suggested that the binding sites in the two proteins are similar (10). At neutral or mildly alkaline pH and in the presence of bicarbonate, both proteins firmly bind two ferric ions per molecule, forming colored complexes which have approximately the same absorption maximum (11-14). It has been shown that the iron-binding capacity of uncomplexed conalbumin is markedly diminished by a variety of chemical procedures which include iodination. This suggests that the specific interaction between metal and protein depends on the structural integrity of the latter (15). However, Azari and Feeney (16, 17) have recently