Hepcidin

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Hepcidin is a peptide hormone produced in the liver, which appears to be the "master" control mechanism of human iron metabolism. It also affects enterocytes, but also macrophages and the liver. Originally thought to be an antibacterial substance, [1] it is now believed to be an inhibitor of iron intake into the body, [2] by binding to and inactivating ferroportin, according to an August 2008 paper in Cell Metabolism.[3]

It is usually a 25-amino-acid sequence, although shorter 22 and 20 amino acid peptides are also present. "The main peptide is notable for containing eight cysteine residues linked as four disulphide bridges resulting in a molecule with a simple hairpin structure and the bridges in a ladder-like configuration. This structure is characteristic of peptides capable of disrupting bacterial membranes and is similar to other antimicrobial peptides." Work in 2001 revealed that in mice, iron loading influenced hepcidin synthesis. [4]

Hepcidin production in the liver is triggered, in part, by inflammatory cytokines such as interleukin-6. A rationale for the down-regulation of iron metabolism in the presence of tumor or infection is that it denies nutrient iron to the pathological cells. Prolonged hepcidin overexpression can lead to clinical anemia, especially anemia of chronic disease but possibly a wider range of anemias.

References

  1. Park CH et al. (2001), "Hepcidin, a Urinary Antimicrobial Peptide Synthesized in the Liver", Journal of Biological Chemistry 276: 7806-7810, DOI:10.1074/jbc.M008922200
  2. Ganz T, Nemeth E (2005), "Iron imports. IV. Hepcidin and regulation of body iron metabolism", Am J Physiol Gastrointest Liver Physiol 290: G199–G203, DOI:10.1152/ajpgi.00412.2005
  3. "Key site in iron metabolism aids in diagnosing anemia of chronic disease", eScience, 5 August 2008
  4. Enrico Rossi (2005 August), "Hepcidin - the Iron Regulatory Hormone", Clin Biochem Rev. 26 (3): 47–49