Hepcidin is the master regulator of systemic iron homeostasis. It reduces serum iron by which mechanism?

• A Binds transferrin, preventing iron delivery to erythropoietic precursors
• B Induces lysosomal degradation of ferroportin-1 (FPN1) on enterocytes, macrophages and hepatocytes ✓
• C Inhibits DMT1 (divalent metal transporter-1) in duodenal enterocytes, reducing luminal iron absorption
• D Activates heme oxygenase to degrade heme iron in macrophages

Explanation

Hepcidin (a 25-amino acid peptide hormone synthesised in the liver) binds to its receptor ferroportin-1 (FPN1, the sole known mammalian iron exporter). Hepcidin-FPN1 binding induces FPN1 internalisation and lysosomal degradation, reducing iron export from duodenal enterocytes (less dietary iron absorption), splenic/hepatic macrophages (less recycled iron from senescent RBCs), and hepatocytes (less storage iron release). This lowers serum iron. Hepcidin is elevated in inflammation (via IL-6/JAK-STAT3), iron overload and infection (causing anaemia of chronic disease). Hepcidin deficiency (hereditary hemochromatosis, HFE mutations reducing BMP-SMAD/hepcidin expression) causes iron overload. Hepcidin does not bind transferrin or inhibit DMT1 directly.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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