Lecture 9: Enzyme Inhibition Flashcards
Enzyme inhibitor
Small molecule/ion that binds an enzyme and decreases its activity
Types of reversible inhibitors
- Competitive
- Uncompetitive
- Noncompetitive
Competitive inhibitor mechanism
Binds to free enzyme and competes with substrate to occupy the active site
Characteristics of a competitive inhibitor
Resembles substrate structure/shape without the function; substrate analog or transition state analog (more potent)
Enzyme kinetic parameters under competitive inhibition
No change to Vmax
Increase in Km
Decrease in k_cat / Km (by same amount as noncompetitive)
Features of competitive inhibition
High [S] will overcome competitive inhibitors
Uncompetitive inhibitor mechanism
Binds only the enzyme-substrate complex close to the active site
Characteristics of uncompetitive inhibitor
Lacks resemblance to substrate; distorts active site to render it catalytically inactive
Enzyme kinetic parameters under uncompetitive inhibition
Decrease Vmax and Km by the same proportion
No change to catalytic efficiency
Features of uncompetitive inhibition
Little effect at very low [S]. Inhibition increases with more [S] (more ES formed); can’t be overcome by high [S]
Noncompetitive inhibitor mechanism
Binds both E and ES with same Ki at a different non-active site
Characteristics of non-competitive inhibitor
Lacks structural resemblance to substrate; distorts enzyme structure and prevents alignment of catalytic center
Enzyme kinetic parameters under noncompetitive inhibition
Decreased Vmax
No change to Km
Decreased catalytic efficiency (by same amount as competitive)
Features of noncompetitive inhibition
Has the same rate as a competitive inhibitor at very low [S]; cannot be overcome by high [S]
Match the kinetic curves with the correct reversible inhibitor type
Match the Lineweaver-Burk plots with the correct reversible inhibitor type
Types of irreversible inhibitors
- Group-specific reagents
- Affinity labels (active substrate analog)
- Suicide inhibitors (mechanism-based inhibition)
What is an irreversible inhibitor?
An irreversible inhibitor results in permanent inactivation by forming stable covalent bonds with functional groups involved in enzyme activity
Group-specific reagents
Irreversible inhibitor that covalently binds specific side chains of enzyme residues
Affinity labels
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
Suicide inhibitors
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.
