Relation of ferritin iron to heme synthesis in marrow and reticulocytes.

The reaction of protoporphyrin with iron to form heme is usually studied in intact or lysed cells in the presence of salts of ionic iron. Despite the fact that such iron is utilized for heme synthesis, the form of iron available to erythropoietic cells in the intact animal is that which is present in serum in the form of a highly stable iron-protein complex, transferrin. Results obtained by use of ionic iron are misleading to the extent that such studies bypass the biochemical mechanisms which control the entrance of iron into the cell, and lead to concentrations of intracellular iron much higher than are possible in viva. Jandl et al. (1) have demonstrated tha,t binding of iron by serum transferrin controls the entrance of iron into the reticulocyte, and have also shown that the over-a.11 incorporation of such iron into heme of these cells is dependent on oxidative metabolism. It is likely that the incorporation of serum iron into heme in the reticulocyte requires oxidative energy, both for the entrance of iron into the cell and for the synthesis of the protoporphyrin moiety of heme. The only mechanism of biochemical significance for the release of transferrin-bound iron and its entrance into a cell is that reported by our laboratory (2) for the incorporation of serum iron into ferritin in the hepatic cell. Although the incorporation of ionic iron into ferritin of surviving liver slices appears not to require oxidative energy, it has been demonstrated in vitro as well as in wivo (3) that the corresponding incorporation of serum-bound iron requires the participation of ascorbic acid and adenosine triphosphate. Although Bessis and Breton-Gorius (4, 5) have demonstrated the presence of ferritin in marrow cells and reticulocytes by use of the electron microscope, these observations do not reveal the origin of such ferritin or the relationship between the ferritin iron and heme which is synthesized in these cells. Falbe-Hansen and Lothe (6) have reported evidence for a short-lived nonheme iron intermediate in the passage of iron from transferrin to hemoglobin in rabbit red cells but have not identified this intermediate. In the present study we report the results of experiments which help to clarify the relationship between ferritin iron, originating from the serum, and heme iron in rat marrow and reticulocytes. The results are consistent with the hypothesis that ferritin iron plays an active role as an intermediate between iron originating from the plasma and the heme synthesized by marrow and reticulocytes.