Iron metabolism

• Haem iron


  Iron found in meats
• Non-haem iron


  Iron found in vegetables
• Iron


  • Bound to proteins
  • Released by proteases (e.g. pepsin) and HCl
  • Haem is taken up intact
  • Non-haem iron is transported as Fe(II)
• Iron requirements


  • Men ~1mg/day
  • Women ~2mg/day
  • Pregnant women ~3mg/day
• Iron absorption


  1. Low pH of stomach solubilizes Fe-containing ionic compounds

  2. Ascorbic acid improves Fe solubility in small intestine

  3. Fe transporters facilitate absorption into blood stream
• Transferrin (Tf)


  • Binds and chelates Fe3+ ions
  • Transports Fe to tissues
  • Maintains solubility
  • Keeps Fe ions unreactive
• Transferrin endocytosis


  1. Receptor-mediated (TfR)

  2. Endocytosis results in Fe3+ release

  3. Fe is distributed to many regions of the cell via Fe transporter and/or channels
• Iron usage and storage

  • Usage: Protein components (Haem)
  • Storage: Ferritin (Fe2+)
• Transferrin (Tf) is major carrier of iron in the blood
• Cells need transferrin receptor (TfR) to internalise & use Fe
• Dietary iron absorption


  Reduced from Fe3+ to Fe2+ before DMT1 transport
• Ferroportin


  A transmembrane protein that transports iron from inside a cell to outside
• Hepcidin


  • The "master regulator" of human iron metabolism
  • Binds to ferroportin, leading to internalisation and degradation of cellular ferroportin
  • Causes retention of iron in cell, leads to reduction in iron levels in plasma
• Over-secretion of Hepcidin


  Causes anaemia of chronic disease
• Hepcidin regulation of iron absorption and release

  1. Prevents enterocytes in intestines from secreting iron into hepatic portal system, thereby reducing iron absorption

  2. Prevents iron release from macrophages
• Hepcidin is released from liver in response to inflammatory cytokines
• Transferrin


  Each molecule can carry two iron ions in ferric form (Fe3+)
• Transferrin iron uptake


  1. Transferrin bound with iron encounters transferrin receptor on a cell surface

  2. Binds to it and is transported into the cell in a vesicle

  3. pH of the vesicle is reduced by hydrogen ion pumps (H+ ATPases), causing transferrin to release its iron ions

  4. Receptor (with transferrin still bound) is then transported through endocytic cycle back to cell surface, ready for another round of iron uptake
• Hereditary Haemochromatosis is a disease of Iron overload Caused by mutation in HFE (human haemochromatosis) gene