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Iron Metabolism (Hepatocyte (As in macrophages, iron in hepatocytes is…
Iron Metabolism
Hepatocyte
- As in macrophages, iron in hepatocytes is either stored as ferritin and hemosiderin or exported out of the cell by ferroportin and subsequently oxidized by caeruloplasmin (similar to hephaestin) before binding to transferrin.
- Iron may also enter hepatocytes as ferritin, haem or haemoglobin but these pathways have not been elucidated yet.
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Regulation
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Iron-storage regulator
- On membrane of hepatocytes
- In the abscence of diferric transferrin, TfR1/ HFE complex and apoTfR2 form, which decrease the formation of hepcidin (inhibitor of ferroportin) #
Erythropoietic regulator
- Responds to requirement for erythropoiesis
- A problem occurs when red-cell production in the bone marrow is accelerated because of ineffective erythropoiesis (like thalassaemia!). Absorption of iron is then increased by this regulator and occurs, inappropriately, even when there is systemic iron overload.
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Enterocyte
Digestion
- Fe3+
- Fe3+ in soluble iron complexes reduced to Fe2+ by DcytB in the brush border
- Transported into the duodenal enterocytes by divalent metal transporter-1.
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- Haem
- Enzymatic digestion of haemoglobin and myoglobin
- Haem enters enterocyte through haem cell transport protein
- Within the enterocyte, haem is degraded by haem oxygenase, and Fe2+ is released.
Fe2+ inside enterocytes
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- Or Iron is transported across the basolateral membrane to enter the circulation by ferroportin (inhibited by hepcidin).
- Once in the plasma, Fe2+ is oxidized to Fe3+ by hephaestin
- Fe3+ then binds to transferrin.