Regulation of Iron Metabolism Harnish and Hariom Yadav NATIONAL AGRI FOOD BIOTECHNOLOGY INSTITUTE,MOHALI Email: [e-mail]

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Regulation of Iron MetabolismHarnish and
Hariom YadavNATIONAL AGRI FOOD BIOTECHNOLOGY
INSTITUTE,MOHALIEmail yadavhariom_at_gmail.com
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OBJECTIVES

• Processes involved in iron metabolism.
• Role of HEPICIDIN.
• Diseases caused by Hepicidin deficiency.

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IRON METABOLISM

• Dietary Iron
• Iron is essential element and must be
• precisely regulated.
• On the lumen side of small intestine iron is
  reduced from its ferric form(Fe3) to ferrous
  form(Fe2).
• Ferrous iron is then transported in enterocytes
  by DMT1(divalent metal transporter).

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• Iron can be either stored within the enterocyte
  as ferritin or it can be transferred across the
  basolateral membrane to the plasma by transport
  protein FERROPORTIN1 and MTP1.
• (Requires oxidation of Ferrous to Ferric by
  hephaestin.)

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TRANSPORT PROTEINS

• DMT1 (Divalent Metal Transporter 1)
• (Tranports from lumen into the enterocytes)
• FERROPORTIN1
• (Transports from enterocytes to circulation)

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QUESTION????

• Who is playing the central role in IRON
  METABOLISM??

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ANSWER

• HEPICIDIN is the key regulator of iron in our
  body.

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What is HEPICIDIN??

• Is a peptide hormone which was first identified
  in human urine and plasma in 2000.
• Its molecular weight is 25 Kda.
• Highly folded structure.
• Present in inactive formprohepcidin(60aa) and
  its active form is hepicidin(25aa).

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HEPICIDN

• 25 Amino acid disulfide peptide.

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Hepicidin, Primary regulator

• Increased expression of hepicidin leads to
• Decrease iron absorption and release.
• Mutation Hemochromatosis
• Increased expressionIron deficiency
• Hepicidin mRna expression is increased by
  erythropoetin,hypoxia inflammation.
• Also binds to ferroportin.

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Ferroportin

• The only cellular iron exporter in vertebrates.
• Present in macrophages,placenta and the
  hepatocytes.

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Mechanism of action of hepicidin

• The major mechanism of hepicidin is THE
  REGULATION OF TRANSMEMBRANE IRON TRANSPORT.
• It binds to FERROPORTIN ,forms hepicidin-ferroport
  in complex ,which is degraded in the lysosomes
  and iron is locked inside the cells(mainly
  enterocytes,hepatocytes and macrophages).

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SO

• Hepcidin lowers iron absorption in the intestine
  ,lowers iron releasing from hepatocytes and
  macrophages
• Serum iron is decreased.

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Hepicidin Regulation

• So when hepicidin levels are low ,iron exporting
  cells have abundant ferroportin and thus releases
  iron into plasma.When hepicidin concentration
  increases it binds to ferroportin and thus iron
  is retained in the cells.

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Regulation of Hepicidin

• Hypoxia/Anemia
• Inflammation

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Regulation of Hepcidin synthesis by anemia and
hypoxia

• Oxygen Hepcidin
• Uptake of diet iron
• Iron release from hepatocytes
• Iron release from macrophages

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Regulation of Hepcidin synthesis by inflammation

• Interleukin-6 Hepcidin
• iron anemia of
  chronic disease.
• Generally when iron level ,ROS(Reactive oxygen
  species) that leads to in thiobarbutyric acid
  activation of NF Kappa proteins activates
  IL-6 , hepicidin synthesis

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Disease States

• Hepcidin deficiency, physiological
  Haemochromatosis
• Hepcidin excess anaemia of chronic disease

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The role of Hepcidin in hereditary hemochromatosis

• Hereditary hemochromatosis
• -excessive intestinal iron absorption
• -Saturation of transferrin
• -Iron deposition in vital organs

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Overall summary

• Hepcidin
• -Is a recently discovered liver produced 25
  amino-acid peptide
• -Is a regulator of iron metabolism that controls
  iron absorption and macrophage iron release.
• -Is regulated by erythropoietic needs( ) ,body
  iron stores( ) and inflammation( )

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