IRON IN ERYTHROCYTES

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Haemoglobin

Haemoglobin (Hb) is the iron-containing oxygen-transport metalloprotein in red blood cells.

See animated version of haemoglobin oxy-deoxy conformation change

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Each subunit of haemoglobin is a globular protein with an embedded haem group; each haem group contains an iron atom, and this is responsible for the binding of oxygen through ion-induced dipole forces. Haemoglobin (in mammals) contains four such subunits, each with one haem group. In humans, each haem group is able to bind one oxygen molecule, and thus, one haemoglobin molecule can bind four oxygen molecules.

A haem group consists of an iron (Fe⁺⁺) ion held in a heterocyclic ring, known as a porphyrin. The iron ion, which is the site of oxygen binding, bonds with the four nitrogens in the center of the ring, which all lie in one plane.

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Life cycle of red blood cells

The red blood cells have a lifespan of 120 days, after which the cells are engulfed by macrophages and their iron resirculated. Most of the iron going into haemoglobin synthesis in erythrocyte precursors is in fact resirculated from old cells. This process of iron recycling is carried out by the macrophages of the reticuloendothelial system:
The reticuloendothelial system is part of the immune system, and consists of phagocytic cells located in reticular connective tissue, primarily monocytes and macrophages. These cells accumulate in lymph nodes and the spleen. The Kupffer cells of the liver and tissue histiocytes are also part of the RES.

Iron recycling

Recycling of iron from worn-out erythrocytes is done by the macrophages of the reticuloendothelial system (RES). These macrophages can store iron as part of breaking down and processing haemoglobin from engulfed red blood cells. However, most iron is rapidly recycled (60% within 12 hours) into new haemoglobin after transport to reticulocytes bound to transferrin.

Some (about 10%) circulating erythrocytes are broken down intravascularly (haemolysis)leading to a direct release of haemoglobin into the blood. In this situation haemoglobin and haem is bound by haptoglobin and haemopexin, respectively, and delivered to the liver or RES.

Figure A: Breakdown of worn-out erythrocyte by macrophage and binding of non-haem iron to transferrin for transport. B: Uptake of transferrin in reticulocytes, recycling of the transferrin/transferrin receptor complex to the circulation, and formation of a new haem group from protoporphyrin and iron.

• Iron in ferritin is trivalent, i.e., ferric (Fe³⁺).
• Haemosiderin is so-called 'stainable iron', visible in the light microscope, composed of aggregated ferritin molecules together with other structural elements.
• Labile iron pool consists of low molecular iron compounds (Fe²⁺).