The effect of binding a non-competitive inhibitor is significantly different from binding a competitive inhibitor because there is no competition. In the case of competitive inhibition, the effect of the inhibitor could be reduced and eventually overwhelmed with increasing amounts of substrate.
This was because increasing substrate made increasing percentages of the enzyme active. With non-competitive inhibition, increasing the amount of substrate has no effect on the percentage of enzyme that is active. Indeed, in non-competitive inhibition, the percentage of enzyme inhibited remains the same through all ranges of [S]. This means, then, that non-competitive inhibition effectively reduces the amount of enzyme by the same fixed amount in a typical experiment at every substrate concentration used The effect of this inhibition is shown above.
As you can see, Vmax is reduced in non-competitive inhibition compared to uninhibited reactions. This makes sense if we remember that Vmax is dependent on the amount of enzyme present. Reducing the amount of enzyme present reduces Vmax. Additionally, KM for non-competitively inhibited reactions does not change from that of uninhibited reactions. This is because, as noted previously, one can only measure the KM of active enzymes and KM is a constant for a given enzyme.
Feedback inhibition is a normal biochemical process that makes use of noncompetitive inhibitors to control some enzymatic activity.
In this process, the final product inhibits the enzyme that catalyzes the first step in a series of reactions. Feedback inhibition is used to regulate the synthesis of many amino acids. For example, bacteria synthesize isoleucine from threonine in a series of five enzyme-catalyzed steps.
As the concentration of isoleucine increases, some of it binds as a noncompetitive inhibitor to the first enzyme of the series threonine deaminase , thus bringing about a decrease in the amount of isoleucine being formed.
A third type of enzymatic inhibition is that of uncompetitive inhibition, which has the odd property of a reduced V max as well as a reduced Km. The explanation for these seemingly odd results is due to the fact that the uncompetitive inhibitor binds only to the enzyme-substrate ES complex.
The inhibitor-bound complex forms mostly under concentrations of high substrate and the ES-I complex cannot release product while the inhibitor is bound, thus result in reduced V max. The reduced Km is a bit harder to conceptualize. The answer lies in the fact that the inhibitor-bound complex effectively reduces the concentration of the ES complex. Decreases in free enzyme correspond to an enzyme with greater affinity for its substrate. In competitive inhibition the substrate and the inhibitor compete for the same active site on the enzyme.
With noncompetitive inhibition the substrate and the inhibitor bind to different active sites on the enzyme, forming an enzyme—substrate—inhibitor, or ESI complex. The formation of an ESI complex decreases catalytic efficiency because only the enzyme—substrate complex reacts to form the product.
Finally, in uncompetitive inhibition the inhibitor binds to the enzyme—substrate complex, forming an inactive ESI complex.
An irreversible inhibitor inactivates an enzyme by bonding covalently to a particular group at the active site. The inhibitor-enzyme bond is so strong that the inhibition cannot be reversed by the addition of excess substrate. The reason is that the competitive inhibitor is reducing the amount of active enzyme at lower concentrations of substrate.
It is worth noting that in competitive inhibition, the percentage of inactive enzyme changes drastically over the range of [S] values used. To start, at low [S] values, the greatest percentage of the enzyme is inhibited. At high [S], no significant percentage of enzyme is inhibited. This is not always the case, as we shall see in non-competitive inhibition. Kevin Ahern and Dr. Indira Rajagopal Oregon State University. Reacting the enzyme with a range of concentrations of substrate at different concentrations of a non-competitive inhibitor will give a family of curves as shown below:.
Km is unchanged, but Vmax is reduced:. This is a very rare class of inhibition. An uncompetitive inhibitor binds to the enzyme and enhances the binding of substrate so reducing Km , but the resultant enzyme-inhibitor-substrate complex only undergoes reaction to form the product slowly, so that Vmax is also reduced:.
Reacting the enzyme with a range of concentrations of substrate at different concentrations of an uncompetitive inhibitor will give a family of curves as shown below:. The Lineweaver-Burk double reciprocal plot for this set of data shows a series of parallel lines - both Km and Vmax are reduced:. If the requirement is to increase the intracellular concentration of the substrate, then either a competitive or non-competitive inhibitor will serve, since both will inhibit the utilisation of substrate, so that it accumulates.
However, if the requirement is to decrease the intracellular concentration of the product, then the inhibitor must be non-competitive.
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