Topic 5 - Agonist Mechanisms

Question 1

Two-State Induced Model

Answer 1

Inactive receptor binds to an agonist –> Conformational Change –> Better fits ligand bind forming high affinity bonds with agonist (This is the active form)

Question 2

Conformational Selection

Answer 2

Agonist binds to an already active conformation and shifts the equilibrium to favour the formation of that active conformation

(Ligand is not binding and causing a conformational change, it is just shifting equilibrium

Question 3

Conformational Selection (Affinity)

Answer 3

An agonist has a higher affinity for the pre-active forms of the receptor and will want to bind to them

Question 4

Conformational Selection (Adding more agonist)

Answer 4

More agonists will bind to the pre-active receptor causing a larger shift in the equilibrium to favour more of the activated conformation

Question 5

Conformational Selection (Antagonist)

Answer 5

Does not change the system’s equilibrium

Binds equally well (identical Kd values) to inactive and active forms of the receptor

This means less receptors are available for binding with agonist

Question 6

Conformational Selection (Inverse Agonist)

Answer 6

Agonist has a higher affinity for the inactive form

Once agonist binds to the inactive form the equilibrium shifts towards the inactive conformation

Question 7

Conformational Selection (Partial Agonist)

Answer 7

Even when all receptors are occupied the maximal effect is still small

Question 8

Irreversible Ligand

Answer 8

Bind and render protein inactive

Enzyme inhibitors inactivate enzymes meaning new ones have to be made to recover enzyme activity

Question 9

Irreversible Ligand (Therapeutic Effect)

Answer 9

Drug can continue to have an effect even after it has been completely removed
Inactive enzymes will still be inactive even when drug is gone