Question

I propose to design a new drug which will act as an inhibitor for an enzyme. If I have used all current information about the mechanism of this enzyme to design this inhibitor and I carefully engineer it with similar chemical properties of the transition state, what type of inhibitor am I attempting to engineer and how will I know if I have succeeded?

a. An uncompetitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in Vmax b. A competitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in Vmax c. An uncompetitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in Km d. A competitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in Km

Answer 1

You are attempting to engineer a competitive inhibitor, which is confirmed by collecting kinetic data and observing an increase in Km without a change in Vmax.

Step-by-step explanation:

If you have used all current information about the mechanism of an enzyme to design a drug that mimics the transition state of the enzyme's substrate, you are attempting to create a transition state inhibitor, which is typically considered a type of competitive inhibitor. To determine if you have successfully engineered a competitive inhibitor, collect kinetic data both in the presence and absence of inhibitor. The hallmark of competitive inhibition is that the Vmax (maximum rate of reaction) remains the same because increasing substrate concentration can outcompete the inhibitor, but the Km (Michaelis constant) increases as the apparent affinity of the enzyme for the substrate decreases in the presence of a competitive inhibitor.

Answer 2

d. A competitive inhibitor, collect kinetic daa both in the presence and absence of inhibitor and watch for a change in Km.

Step-by-step explanation:

According to the description, the inhibitor was designed in a way when it binds the enzyme, the transition state achieved will be close to the one observed when the substrate binds.

In other words, the aim was to design an inhibitor that will bind the free enzyme in a reversible way, competing with the substrate for the binding sites.

As the inhibitor will be binding the same site as the substrate, the apparent affinity of the enzyme for the substrate will decrease. And the higher the affinity of the inhibitor for the enzyme, stronger the effect it will have over the affinity of the enzyme for the substrate.

Quantitatively speaking, the apparent Km of the enzyme for the substrate will increase with the inhibitor concentration, as the affinity of the enzyme for the substrate decreases.

In summary, what is being engineered is a competitive inhibitor, and the way of knowing if the design was successful, is collecting kinetic data in presence and absence of inhibitor, and watch for changes in the apparent Km.