Erythroid Iron Metabolism

Iron is indispensable for the proper functioning of virtually all cells in the body. However, red blood cells, which contain approximately 80% of organismal iron, have a particularly intimate relationship with this precious metal. It is safe to say that the iron content of erythroid progenitors (e.g., BFU-Es; please see below) is infi nitesimal compared to the amount of iron in mature erythrocytes that contain approximately 12 × 10 8 atoms per cell [ 1 ] ; hence, the circulating red blood cells hold heme iron in a 20 mM “concentration.” Since the developing red cells acquire iron only from diferric transferrin, which carries iron in plasma in about 3 μ M concentrations, they have the capacity to increase this concentration 7,000-fold. Based on the value of 2.5 μ g non-heme Fe per 100 mL erythrocytes [ 2 ] , non-heme iron concentrations in erythrocytes are ~40,000-fold lower than those of heme iron. Additionally, the effi cacy with which immature red blood cells convert transferrin-borne iron into hemoglobin iron is amazingly high [ 3, 4 ] . In the experience of these authors, reticulocytes (immediate progenitors of mature red cells) take up roughly 10 pmol Fe/10 6 cells/h from diferric transferrin, corresponding to 6 × 10 6 atoms Fe/cell/h. Considering the above value of 12 × 10 8 atoms Fe per erythrocyte, it takes approximately 200 h (or 8.3 days) for iron to accumulate in total erythrocyte hemoglobin. This interval is slightly longer than the average erythroid cell maturation time (~5–6 days) but, since iron uptake by reticulocytes is probably somewhat slower than in bone marrow erythroblasts, the agreement is remarkably close. It needs to be pointed out that the rate with which iron is removed from the circulation by the developing erythroid cells is, under normal conditions, identical to the rate with which iron is released from macrophages following phagocytosis of senescent Chapter 10 Erythroid Iron Metabolism