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Hepcidin

German: Hepcidin

1 Definition

Hepcidin is a protein that plays a key role in the body's iron metabolism. It inhibits the iron transporter ferroportin which leads to reduced gastrointestinal iron absorption as well as decreased iron release from the mononuclear phagocyte system (MPS).

2 Physiology

The main production site of hepcidin is the liver. The biologically active form of hepcidin is synthesized from several precursors and is a rather small peptide consisting of 25 amino acids. Iron absorption and inflammation increase hepcidin production whereas increased erythropoiesis inhibits the process. When hepcidin binds to ferroportin, the degradation rate of ferroportin increases.

3 Clinical significance

3.1 Primary hepcidin deficiency

A primary hepcidin deficiency is the result of damage to the hepcidin coding HAMP gene.

3.2 Secondary hepcidin deficiency

Secondary hepcidin deficiencies result from genetic defects to the hepcidin protein itself or can be acquired by liver dysfunction (e.g. hepatic cirrhosis).

Decreased hepcidin activity in the context of hereditary hemochromatosis (iron overload) leads to increased iron absorption to the enterocytes. Excess iron binds to ferritin complexes, allowing it to enter the blood stream. The lysosomal compartment of hepatocytes subsequently absorbs it, here it is converted to hemosiderin which results in cell damage.

3.3 Anemia

Secretion of interleukin 6 is increased in conjunction with chronic inflammation which leads to increased release of hepcidin in the liver. The decreased gastrointestinal resorption of iron caused by hepcidin can result in disrupted iron distribution which manifests itself as Anemia of Chronic Disease (ACD).

It is suspected that hepcidin might also play a role in renal anemia because its concentration is increased in patients with kidney failure.

4 Literature

Nemeth E, Ganz T: The Role of Hepcidin in Iron Metabolism Acta Haematol 2009;122:78–86 (free access, , retrieved 20 April 2016)

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