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Hereditary Hemochromatosis

An Algorithmic Approach to Diagnosis



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Iron Absorption, Conservation and Transport by Hepatocyte

Slide 10

January 2009

Let’s now zoom in to an hepatocyte. Focus your attention on the transferrin bound ferric iron in the central vein. Like the crypt cell, the hepatocyte facilitates iron absorption through formation of a complex of beta-2 microglobulin with membrane bound HFE and transferrin receptor-1 proteins. This complex facilitates the uptake of iron through endocytosis. There is a second iron uptake process that involves transferrin receptor‑2. The affinity of ferric iron for transferrin receptor‑1 is approximately 30 times higher than the affinity of ferric iron for transferrin receptor-2. Endocytosis of iron involving the complex of beta-2 microglobulin, HFE and Transferrin Receptor-1 stimulates the release of interleukin 2 which signals the nucleus to initiate transcription and translation of the protein hepciden or a juvenile protein called hemojuvulin. Hepatocytes also continuously release ceruloplasmin and transferrin into circulating blood plasma.  Endocytic iron is transported into the cellular iron pool by DMT1. Iron is also taken up into the lysosome where it binds to apoferritin to create the prevalent iron storage complex called ferritin. When this complex is stored in the lysosome, it is referred to as hemosiderin. Iron in the cellular pool is recirculated back into the blood serum by the transporter ferroportin. Ferrous iron is converted to ferric iron by ceruloplasmin and that iron binds to transferrin where it circulates in the plasma pool. A small fraction of cellular iron is also transported into the bile duct by ferroportin where it is excreted into the bowel.

Iron Absorption by Hepatocyte

 


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