Lecture 9: Enzyme Inhibition

Question 1

Enzyme inhibitor

Answer 1

Small molecule/ion that binds an enzyme and decreases its activity

Question 2

Types of reversible inhibitors

Answer 2

1. Competitive
2. Uncompetitive
3. Noncompetitive

Question 3

Competitive inhibitor mechanism

Answer 3

Binds to free enzyme and competes with substrate to occupy the active site

Question 4

Characteristics of a competitive inhibitor

Answer 4

Resembles substrate structure/shape without the function; substrate analog or transition state analog (more potent)

Question 5

Enzyme kinetic parameters under competitive inhibition

Answer 5

No change to Vmax
Increase in Km
Decrease in k_cat / Km (by same amount as noncompetitive)

Question 6

Features of competitive inhibition

Answer 6

High [S] will overcome competitive inhibitors

Question 7

Uncompetitive inhibitor mechanism

Answer 7

Binds only the enzyme-substrate complex close to the active site

Question 8

Characteristics of uncompetitive inhibitor

Answer 8

Lacks resemblance to substrate; distorts active site to render it catalytically inactive

Question 9

Enzyme kinetic parameters under uncompetitive inhibition

Answer 9

Decrease Vmax and Km by the same proportion
No change to catalytic efficiency

Question 10

Features of uncompetitive inhibition

Answer 10

Little effect at very low [S]. Inhibition increases with more [S] (more ES formed); can’t be overcome by high [S]

Question 11

Noncompetitive inhibitor mechanism

Answer 11

Binds both E and ES with same Ki at a different non-active site

Question 12

Characteristics of non-competitive inhibitor

Answer 12

Lacks structural resemblance to substrate; distorts enzyme structure and prevents alignment of catalytic center

Question 13

Enzyme kinetic parameters under noncompetitive inhibition

Answer 13

Decreased Vmax
No change to Km
Decreased catalytic efficiency (by same amount as competitive)

Question 14

Features of noncompetitive inhibition

Answer 14

Has the same rate as a competitive inhibitor at very low [S]; cannot be overcome by high [S]

Question 15

Match the kinetic curves with the correct reversible inhibitor type

Answer 15

Question 16

Match the Lineweaver-Burk plots with the correct reversible inhibitor type

Answer 16

Question 17

Types of irreversible inhibitors

Answer 17

1. Group-specific reagents
2. Affinity labels (active substrate analog)
3. Suicide inhibitors (mechanism-based inhibition)

Question 18

What is an irreversible inhibitor?

Answer 18

An irreversible inhibitor results in permanent inactivation by forming stable covalent bonds with functional groups involved in enzyme activity

Question 19

Group-specific reagents

Answer 19

Irreversible inhibitor that covalently binds specific side chains of enzyme residues

Question 20

Affinity labels

Answer 20

AKA active substrate analog. Irreversible inhibitor that is structurally similar to substrate and covalently binds active site. More specific for active site vs group-specific reagents

Question 21

Suicide inhibitors

Answer 21

AKA mechanism-based inhibition. Binds active site and produces reactive intermediate that covalently modifies enzyme -> permanent inactivation. “Tricks” enzyme into catalytic mechanism. Most specific for active site of all irreversible inhibitors.