The Role of Haemoglobin

• Haemoglobin is a globular protein found in vast quantities in red blood cells.
• It has a quaternary structure as there are four polypeptide chains. These chains or subunits are globin proteins (two α–globins and two β–globins), and each subunit has a prosthetic (non-protein) haem group.
• The four globin subunits are held together by disulphide bridges.  The hydrophobic R groups face inwards (to maintain the 3D shape) and the hydrophilic R groups face outwards (to maintain solubility).
• The arrangement of the R groups is important to the functioning of haemoglobin. In sickle cell anaemia, a DNA base substitution results in the amino acid valine (non-polar) replacing glutamic acid (polar), and the resulting haemoglobin is less soluble.
• The prosthetic haem group contains an iron II ion (Fe2+) which reversibly combines with an oxygen molecule, forming oxyhaemoglobin.  This results in the haemoglobin appearing bright red.
• Each haemoglobin with the four haem groups can therefore carry four oxygen molecules.
• Haemoglobin is responsible for binding oxygen in the lungs, and transporting the oxygen to tissues to be used in aerobic metabolic pathways.
• As oxygen is not very soluble in water and haemoglobin is, oxygen can be carried more efficiently around the body when bound to haemoglobin.
• The presence of the haem group (and Fe2+) enables small molecules like oxygen to be bound more easily because as each oxygen molecule binds it alters the quaternary structure (due to alterations in the tertiary structure) of the protein. This causes haemoglobin to have a higher affinity for the subsequent oxygen molecules and they bind more easily.
• None of the amino acids that make up the polypeptide chains in haemoglobin are well suited to binding with oxygen. The existence of the iron II ion (Fe2+) in the prosthetic haem group allows oxygen to reversibly bind.
• 1. Transport of oxygen

  The majority of oxygen transported around the body is bound to the protein haemoglobin in red blood cells (also known as erythrocytes). Each molecule of haemoglobin contains four haem groups, each able to bond with one molecule of oxygen.  This means that each molecule of haemoglobin can carry four oxygen molecules, or eight oxygen atoms in total.
• When oxygen binds to haemoglobin, oxyhaemoglobin is formed:

    oxygen  + haemoglobin  ⇌  oxyhaemoglobin                      

  4O2     +           Hb             ⇌         HbO8
• The binding of the first oxygen molecule results in a conformational change in the structure of the haemoglobin molecule, making it easier for each successive oxygen molecules to bind. This is known as cooperative binding. The reverse of this process happens when oxygen dissociates in the tissues.
• 2. Transport of carbon dioxide

  Waste carbon dioxide produced during respiration diffuses from tissues into the blood. There are three main ways in which carbon dioxide is transported around the body.
• 1. Approximately 10% of carbon dioxide dissolves directly in the blood plasma and is transported in solution3-)
  2. Approximately 20% of carbon dioxide bind to haemoglobin, forming carbaminohaemoglobin
  3. Approximately 70% of carbon dioxide is transported in the form of hydrogen carbonate ions (HCO