However, erythrophagocytosis is not the only way for macrophages to acquire iron. The major source of plasma iron comes from macrophages that recycle iron from senescent or damaged erythrocytes rather than from intestinal iron absorption ( Knutson & Wessling-Resnick, 2003). Enns, in Current Topics in Membranes, 2012 2.2 Heme and Hb Receptors In the erythroid cells, most of the iron released from the endosomes is transported into mitochondria for heme synthesis in nonerythroid cells, and the iron is stored predominantly as ferritin.

The process is therefore unlike that of low-density lipoprotein receptor-mediated internalization ( Chapter 18). In this type of receptor-mediated endocytosis of transferrin–transferrin receptor complex, the endosomes do not come into contact with lysosomes. Both apotransferrin (and a fraction of ironbound transferrin) and transferrin receptor are returned to cell surfaces for reuse. In the acidified endosomes, DMT1 facilitates iron transport into the cytosol. In the endosomes, a proton pump acidifies the complex to pH 5.4, and by altering the conformation of proteins, iron is released from transferrin bound to transferrin receptor. The next step is the internalization of the transferrin–transferrin receptor-HFE protein complex with formation of endosomes. The process begins in clathrin-coated pits with the binding of diferric transferrin to specific plasma membrane transferrin receptor. Unloading of iron to immature erythroid cells is by receptor-mediated endocytosis.

Iron in excess of this requirement is stored as ferritin and hemo-siderin. The bulk of transferrin iron is delivered to immature erythroid cells for utilization in heme synthesis. The binding is extremely strong under physiological conditions. Each molecule of transferrin can bind two Fe 3+ ions. Transferrin is synthesized primarily in the liver. Over 95% of plasma iron is in the Fe 3+ state bound to the glycoprotein transferrin, a monomeric β 1-globulin (M.W. Bhagavan, Chung-Eun Ha, in Essentials of Medical Biochemistry, 2011 Plasma Iron Transport

Blood and iron new west