Reticulocytes iron release from transferrin

Mechanism and Regulation of Iron Release from Transferrin to Reticulocytes... 

Iron released from the intestinal mucosa enters the portal blood where it combines with an iron-transporting /5-globulin known as transferrin which distributes the iron throughout the body. Most of it is taken up by the reticulocytes for haemoglobin formation. 

Other mechanisms are also involved in the reticulocyte-mediated release of iron from transferrin, and its subsequent incorporation into heme. Intact oxidation-reduction pathways are essential and seem to operate at a step following the attack on the anion (90). Heme exerts an inhibitory influence on iron transfer from protein to cell, seemingly by interfering at an early stage in the release of the metal from transferrin (89). Non-transferrin carriers for iron have also been identified in the reticulocyte and may participate in its incorporation into heme (81). 

The iron inserted into apo-heme is acquired from the transferrin circulating in the bloodstream. Transferrin is taken up by cells according to their need for iron. This transport is mediated by a membrane-boimd protein of the plasma membrane called the transferrin receptor. The erythropoietic cell contains a large number of transferrin receptors in its plasma membrane. Stem cells contain very few transferrin receptors because of their lack of hemoglobin synthesis. The normoblast contains 0.3 to 0.8 million transferrin receptors, whereas the more mature reticulocyte contains 0.1 million receptors. After release of iron, transferrin returns to the bloodstream. Most of the transferrin contains iron derived from recently catabolized red blood cells, as shown in Figure 10.33. About 99% of the transferrin contains iron acquired from macrophages, where old red blood cells are dismantled only 1% is derived from recently absorbed dietary iron. 

Schulman, H.M., Martinez-Medellin, J., Sidloi, R. The reticulocyte-mediated release of iron and bicarbonate from transferrin Effect of metabolic inhibitors. Biochim. biophys. Acta (Amst.) 343, 529-534 (1974)... 

The dwell time of a transferrin molecule with the reticulocyte may be only a minute or two (52, 80) or possibly as long as 10 min (86), after which the protein is released for another cycle of iron transport. The affinity of reticulocyte receptors for apotransferrin appears less than for iron-loaded molecules (80). This property may facilitate the release of the protein from the receptor after it has donated its iron and ensures that the apoprotein will not impede the delivery of iron to reticulocytes by competing with iron-bearing molecules for available receptors on the cell surface. 

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