Question

Given below are two statements, one is labelled as Assertion A and the other is labelled as Reason R
Assertion A : The uncompetitive inhibitors bind only to the enzyme-substrate (ES) complex and not to the free enzyme.
Reason R : Binding of the substrate to the enzyme causes a change in its conformation, which reveals the inhibitor-binding site.
In light of the above statements, choose the correct answer from the options given below

• A. Both A and R are true and R is the correct explanation of A
• B. Both A and R are true but R is NOT the correct explanation of A
• C. A is true but R is false
• D. A is false but R is true

Hint:

An uncompetitive inhibitor is like a lock that only appears after the key (substrate) is inserted into the door (enzyme). The binding of the substrate "reveals" the inhibitor's pocket, explaining why it cannot bind to the free enzyme alone.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Uncompetitive inhibition is a distinct class of reversible enzyme inhibition.
Unlike competitive inhibitors, an uncompetitive inhibitor does not compete with the substrate for the active site of the free enzyme.
Instead, its action is completely dependent on the prior binding of the substrate to the enzyme.

Step 2: Detailed Explanation:
Let us analyze the biophysical mechanism of uncompetitive inhibition:
Assertion A Analysis: By definition, an uncompetitive inhibitor has no affinity for the free enzyme (E).
It binds exclusively to the enzyme-substrate (ES) complex to form an inactive ternary ESI complex.
This prevents the catalytic cycle from proceeding to form products.
Therefore, Assertion A is correct.
Reason R Analysis: The biochemical reason why the inhibitor cannot bind to the free enzyme lies in the induced-fit model of enzyme-substrate interaction.
In the free enzyme state, the specific binding site (or pocket) for the uncompetitive inhibitor does not exist or is structurally inaccessible.
When the substrate binds to the active site, it induces a conformational change in the enzyme's structure.
This structural rearrangement alters the spatial distribution of amino acid residues, creating or revealing a functional allosteric binding pocket for the inhibitor.
Therefore, the prior binding of the substrate is a prerequisite for inhibitor binding.
Thus, Reason R is correct and directly explains why the inhibitor binds only to the ES complex.

Step 3: Final Answer:
Both statements are true, and R is the correct biochemical explanation of A, which corresponds to option (A).