Allostery in haemoglobin

Haemoglobin is an allosteric protein. This means that the binding of oxygen to one of the subunits is affected by its interactions with the other subunits. In fact the binding of oxygen to one haemoglobin subunit induces conformational changes (discussed before) that are relayed to the other subunits, making them more able to bind oxygen by raising their affinity for this molecule. Thus the binding of oxygen to haemoglobin is said to be cooperative. In contrast the binding of oxygen to the single polypeptide chain of myoglobin is noncooperative. This is clearly shown by the oxygen dissociation curves of the two molecules.

The curve for haemoglobin is said to be sigmoidal, which reflects its cooperative binding, whereas that for myoglobin is hyperbolic which reflects noncooperative binding. From the oxygen dissociation curve it can also be seen that for any particular oxygen partial pressure the degree of saturation of myoglobin is always higher than haemoglobin. Myoglobin therefore has a higher affinity for oxygen than does haemoglobin. This reflects the different functions of the two oxygen binding proteins. For example in blood capillaries (partial pressure of oxygen is approx 20 mmHg)  haemoglobin will release its oxygen to myoglobin for storage there.

Fetal haemoglobin also has a high affinity for oxygen to supply the developing fetus with sufficient oxygen from the mothers blood.

The diagrams above illustrate gaseous exchange in the alveoli of the lungs (binding of oxygen and release of carbon dioxide) and in respiring tissue (release of oxygen and binding of carbon dioxide.

The binding of oxygen to haemoglobin is affected by the concentration of H+ ions and carbon dioxide in the surrounding tissue, this is called the Bhor effect. In actively metabolizing tissue, such as muscle, the concentrations of these species are relatively high. This effectively causes a shift of the oxygen dissociation curve for haemoglobin to the right, promoting the release of oxygen. This comes about by proton binding sites which have a higher affinity for binding H+  in deoxyhaemoglobin than in oxy haemoglobin. An increase in carbon dioxide also causes an increase in protons due to the action of the enzyme carbonic anhydrase which catalyses the reaction:

CO2  +  H2O  <===>   HCO -3   +   H+ 

In addition carbon dioxide can also react with primary amino groups in the polypeptide chain to form a negatively charged carbamate. Again, this change from a positive to a negative charge favours the conformation of deoxyhaemoglobin. On returning to the lungs, the concentrations of protons and carbon dioxide are lower than in respiring tissue, so that the process is reversed and oxygen binds to haemoglobin.