INCORPORATION OF IRON IN HEMOGLOBIN MOLECULE 623 



iron is incorporated in the hemoglobin of new red cells with remark- 

 able speed. After four hours it was detected in the erythrocytes; 

 after 24 hours one-third of the absorbed iron was incorporated in 

 hemoglobin and in a few days the utilization was complete. The 

 radioactive iron in the blood is in the form of hemoglobin not in 

 that of inorganic or easily detachable iron (Miller and Hahn, 1950). 

 In the human fetus, the formation of hemoglobin appears to be even 

 faster than in the mother; more of the radioactive iron given to the 

 mother shortly before termination of pregnancy was taken up by the 

 fetal erythrocytes than by those of the mother {2168). 



Similar results have been obtained with rats by Copp and Green- 

 berg {1^89). They demonstrated the great rapidity with which the 

 bone marrow takes up radioactive iron, given per os or intravenously. 

 The maximum of iron concentration in the marrow is reached in less 

 than one day and is followed by a fast decline due to the removal of 

 the iron in form of erythrocyte hemoglobin, with a half-time of one 

 to two days. In the recovery of rats from anemia the hemoglobin 

 synthesis is still faster U89,1804). Scott and McCoy (2520) calculate 

 that the total iron of rat bone marrow can be transformed to hemo- 

 globin in one to two hours, the rate being perhaps even faster at the 

 height of hemopoiesis. 



In humans, however, the rate of hemoglobin synthesis in recovery 

 from a mild degree of anemia, for instance in blood donors, is far 

 less rapid (c/., e.g., 927). Evidently only a small part of the iron 

 absorbed from the intestine is used for hemoglobin synthesis; a 

 large part is stored (339,926,2226). The conditions under which the 

 storage iron in the organs is released for hemoglobin synthesis in the 

 bone marrow, and the transformation it undergoes before it is incor- 

 porated, in the hemoglobin molecule in the red cells of the bone 

 marrow are still incompletely understood. From studies with radio- 

 active iron, Fe*', Greenberg and Wintrobe (10^8) conclude that in 

 man about 130 mg. of iron constitute a metabolic iron pool which is 

 readily available for hemoglobin synthesis. 



Barer and Fowler (14^,926) observed that the initial increase of hemoglobin 

 in blood donors or anemic patients on iron therapy is followed by a decrease 

 even if iron therapy is continued. Also iron fails to accelerate recovery of 

 hemoglobin in blood donors after repeated bleedings followed by iron therapy. 

 These observations have been taken as evidence for assuming that iron 

 stimulates hemoglobin formation in addition to supplying a building stone 

 for hemoglobin synthesis. It is, however, not clear why the iron stimulus 

 should cease. Similar conclusions were drawn by Heilmeyer and Plotner 



