Guinea pig and human red cell hemolysates release iron from transferrin.

Despite a binding constant of 10(22) L/mol-1, iron is released from transferrin in the reticulocyte. The mechanism of this release is unclear. It has been suggested that iron is released from transferrin in endocytic vesicles that have been acidified. But the carboxy-terminal iron in transferrin is acid stable at the pH apparently achieved in the endocytic vesicle, and is, nevertheless, released. We found that red cell hemolysates, at neutral pH, will release iron from transferrin. With molecular sieve chromatography, the activity is seen to consist of high and low molecular weight components. The activity of both components is susceptible to destruction by phosphatases. The releasing activity of hemolysates can account for about 25% of the iron uptake of a reticulocyte at pH 7; at pH 5.5 (the purported pH of the endocytic vesicle), the releasing activity is sufficient to account for all the iron taken by the reticulocyte.