An inhibitor is defined as a substance which binds with the enzyme and brings about a decrease in catalytic activity of that enzyme. For example, anti-oxidants are added as inhibitors to food to retard its spoilage on exposure to air (oxygen) and inhibition could be either reversible or irreversible.
Allosteric activators and inhibitors:
This type of inhibition takes place due to the presence of allosteric site (Greek allo
‘other’; stereos = ‘space’ or ‘site’) on the surface of the enzyme away from the active site. The final end-product fits in the allosteric site and in some way brings about a change in shape of the enzyme so that the active site of the enzyme becomes unfit for making a complex with its substrate. Allosteric inhibition may be reversible. In many metabolic reactions, when the concentration of the final end product (usually acts as an allosteric inhibitor) in the cell falls and the activity of the enzyme is restored. Similary an enzyme can also be activated by an activator that binds to an allosteric site. This activator is called as an allosteric activator.
A competitive inhibition usually is reversible. A competitive inhibitor usually closely resembles the substrate and is regarded as substrate analogue. The inhibitor competes with substrate and binds at the active site of the enzyme but does not undergo any catalysis. As long as the competitive inhibitor is bound to the active site, the enzyme will not be available for the substrate to bind. This type of inhibition can be reversed by increasing the concentration of substrate.
Example: 1) Enzyme - Xanthine oxidase; Substrate - Hypoxanthine; Inhibitor – Allopurinol.
Significance of the inhibitor: Used in the control of Gout to reduce excess production of uric acid from hypoxanthine.
Example: 2) Enzyme - Succinate dehydrogenase; Substrate - Succnate; Inhibitor - Malonate
Usually a noncompetitive inhibitor binds either to free enzyme or to ES complex at a site other than the active site on the enzyme surface. This results in the change of conformation of the enzyme as well as its active site, which makes the substrate unable to bind to the enzyme effectively. This type of inhibitor has no structural resemblance with the substrate like competitive inhibitors.
Non-competitive inhibitors do not interfere with the enzyme-substrate binding. But catalysis is prevented, possibly due to the distortion of enzyme conformation.
Uncompetitive inhibitors binds only to the ES complex. However, the binding of the inhibitor affects the binding of the substrate. This type of inhibition cannot be overcome. The inhibitor usually follows an allosteric effect where it binds to a different site on the enzyme than the substrate. This binding to an allosteric site changes the conformation of the enzyme so that the affinity of the substrate for the active site is reduced.