Question

Some enzymes are said to be “allosterically regulated”. Using haemoglobin or phosphofructokinase (PFK) as examples, explain the concept of allosteric regulation. Provide at least one example illustrating the physiological relevance of allosteric regulation

Answer 1

Ans) The regulation of an enzyme activity by binding of an effector molecule at a site other than the enzyme's active site (known as allosteric site or regulatory site) is known as allosteric regulation. This mechanism helps in regulating the rates of various metabolic pathways in a cell. It is a reversible process since the effector binding to enzyme is non covalent and can be seen only in case of enzymes which have multiple active sites.

Haemoglobin is a allosteric protein with multiple active sites, in which binding of oxygen to one of the sub units is affected by its interactions with the other sub units by inducing conformational changes in the sub units making them more able to bind oxygen by raising their affinity for this molecule. Since it is a reversible mechanism, the oxygen bound to haemoglobin is released in the blood capillaries where partial pressure of oxygen is less, resulting in deoxy haemoglobin.

The binding of oxygen is affected by the concentration of H⁺ ions and carbondioxide in the surrounding tissues, this is called the Bhor effect. In muscle tissue where the concentration of H⁺ and CO₂ are relatively high the proton binding sites of deoxy haemoglobin have a higher affinity for binding H⁺ than in oxy haemoglobin. An increase in carbondioxide also causes an increase in protons due to the action of the enzyme carbonic anhydrase. In addition carbon dioxide can also react with amino groups in polypetide chain to form a negatively charged carbamate whose negative charge favors the conformation of deoxyhaemoglobin. While in lungs, where the concentration of proton and carbondioxide are less, the process is reversed and oxygen binds to haemoglobin. In this manner the allosteric regulation plays a role in regulating the physiological activities of haemoglobin.