9. What does allosteric inhibition of an enzyme by a ligand mean?
a. The binding of a ligand to the enzyme inhibits the binding of
cognate substrate at the same binding site
b. The binding of a ligand to the enzyme inhibits the
binding of the cognate substrate at the different binding
site
c. Ligand binds with protein covalently
d. All the binding sites are occupied by the ligand

The correct answer is: b. The binding of a ligand to the enzyme inhibits the binding of the cognate substrate at a different binding site.​

Introduction

Allosteric inhibition of an enzyme by a ligand is a key regulatory strategy in metabolism, where a molecule binds at a site other than the active site and decreases enzyme activity. This indirect modulation through conformational change allows cells to finely control pathway flux without directly competing with the substrate at the catalytic site.​

What Is Allosteric Inhibition?

Allosteric inhibition is a form of enzyme inhibition in which an inhibitor (ligand) binds to a specific allosteric site that is spatially distinct from the active site. Binding at this non‑catalytic site alters the three‑dimensional conformation of the enzyme, typically decreasing substrate affinity or catalytic efficiency at the active site.​

In many allosteric enzymes, this inhibition is reversible and part of feedback control, where an end product of a pathway down‑regulates an earlier enzyme by allosteric binding. This regulation is crucial for maintaining homeostasis and preventing overproduction of metabolites.​

Detailed MCQ Solution

Question: What does allosteric inhibition of an enzyme by a ligand mean?

a. The binding of a ligand to the enzyme inhibits the binding of cognate substrate at the same binding site
b. The binding of a ligand to the enzyme inhibits the binding of the cognate substrate at the different binding site
c. Ligand binds with protein covalently
d. All the binding sites are occupied by the ligand

Option (a) – Same binding site

This statement describes competitive inhibition, not allosteric inhibition. In competitive inhibition, the inhibitor resembles the substrate and binds at the active site, directly competing with the substrate for the same site. Allosteric inhibition, in contrast, involves binding at a different, non‑catalytic site, so option (a) is incorrect.​

Option (b) – Different binding site (Correct)

In allosteric inhibition, the ligand (allosteric inhibitor) binds to a site different from the active site, termed the allosteric site. This binding induces a conformational change that reduces the ability of the active site to bind the cognate substrate or to catalyze the reaction efficiently, thus inhibiting enzyme activity. Therefore, option (b) correctly reflects the concept of allosteric inhibition and is the right answer.​

Option (c) – Covalent binding

Covalent binding of an inhibitor is characteristic of irreversible inhibition, where the enzyme is permanently inactivated by covalent modification of critical residues at or near the active site. Allosteric inhibitors generally bind non‑covalently (via hydrogen bonds, ionic interactions, hydrophobic interactions) and their effect is usually reversible. Thus, option (c) does not define allosteric inhibition.​

Option (d) – All binding sites occupied

This option suggests a scenario like saturation or multiple site occupancy but does not describe the mechanism of allosteric inhibition. Allosteric inhibition is defined by where and how the ligand binds (at a distinct allosteric site causing conformational change), not by the mere fact that all binding sites are occupied. Hence, option (d) is incorrect as a definition.​

Key Features of Allosteric Inhibition

• The inhibitor binds at a non‑catalytic, allosteric site, not at the active site.​

• Binding alters enzyme conformation and usually decreases substrate affinity or turnover number at the active site.​

• Often exhibits non‑competitive or mixed‑type kinetic behavior, because inhibitor binding is not simply displaced by increasing substrate concentration.​

• Frequently involved in feedback inhibition where pathway end products regulate key enzymes.​

Short Enzyme Inhibition Comparison