Hereditary haemochromatosis (HFE-associated) results in excessive dietary iron absorption. The molecular mechanism involves defective HFE protein failing to upregulate which hepatic hormone that normally reduces ferroportin-mediated iron export from enterocytes and macrophages?
- A Erythropoietin (EPO)
- B Transferrin
- C Hepcidin (HAMP) ✓
- D Lactoferrin
Explanation
HFE protein associates with transferrin receptor 1/2 on hepatocytes to sense circulating iron (as diferric transferrin). Wild-type HFE promotes BMP-SMAD signalling, upregulating hepcidin expression. Hepcidin (25 aa peptide hormone from hepatocytes) binds ferroportin on enterocytes, macrophages, and hepatocytes, causing its internalisation and degradation, thus blocking iron export into plasma. In HFE mutations (C282Y most common), hepcidin remains inappropriately low, ferroportin is overactive, iron absorption is unregulated, and iron accumulates in parenchymal cells (liver, heart, pancreas, gonads). EPO and erythroferrone suppress hepcidin in iron-deficiency anaemia/erythroid expansion. Transferrin is the transport protein; lactoferrin is in secretions.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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