Competitive and Non-Competitive Enzyme Inhibitors
Competitive Inhibitors
These are structurally similar to the substrate of the enzyme and bind to the active site. This means that when a competitive inhibitor binds to the active site of an enzyme, it prevents the substrate from binding. Only once the inhibitor has been released can the substrate bind. The inhibitor is called a competitive inhibitor as it competes with the substrate for the active site.
The effects of a competitive inhibitor can be reduced by increasing the substrate concentration. More substrate molecules would successfully bind to the active site than inhibitor molecules, therefore reducing the effect of the inhibition. The maximum rate of reaction, or a level very close to it, can be reached.
Non-Competitive Inhibition
These are not similar to the substrate and do not bind to the active site. Instead, they bind to a different site on the enzyme and change the conformation of the active site. The substrate may still be able to bind, however, the enzyme is not able to catalyze the reaction, or can only do so at a slower rate.
In the presence of a non-competitive inhibitor, increasing the substrate concentration cannot prevent the inhibitor from binding, as the two bind to different sites. Therefore, no matter how high the concentration of substrate is, some of the enzymes will still be inhibited. The maximum rate of reaction will always be lower in the presence of a non-competitive inhibitor.
An example of a non-competitive inhibitor is ATP. When ATP accumulates, it binds to a site other than the active site on the enzyme phosphofructokinase. In doing so, it changes the enzyme’s conformation and lowers the rate of reaction so that less ATP is produced.
End-Product Inhibition
Metabolic pathways are made up of many chemical reactions, and these reactions are catalyzed by enzymes. Often, the product of the last reaction in the pathway inhibits the enzyme that catalyzes the first reaction. This is called end-product inhibition and it involves non-competitive inhibitors.
The product of the last reaction of the metabolic pathway will bind to a site other than the active site of the enzyme that catalyzes the first reaction. This site is called the allosteric site. When it binds to the allosteric site, it acts as a non-competitive inhibitor and changes the conformation of the active site. Therefore, it makes the binding of the substrate to the enzyme unlikely. Once the inhibitor is released from the allosteric site, the active site returns to its original conformation, and the substrate is able to bind again.
There is a clear advantage in using end-product inhibition for controlling metabolic pathways. When there is an excess of end-product, the whole metabolic pathway is shut down as the end-product inhibits the first enzyme. Therefore, less of the end-product is produced, and by inhibiting the first enzyme, it also prevents the formation of intermediates. When the levels of the end-product decrease, the enzymes start to work again, and the metabolic pathway is switched on.