Enzyme inhibition Flashcards
Two main categories/classes of inhibitors
Irreversibel
Reversible
Definition of inhibitors
Molecules that interfere with catalysis, slowing or halting enzymatic reactions
3 types of reversible inhibitors
Competitive
Uncompetitive
Noncompetitive
Difference between uncompetitive and noncompetitive inhibition
Uncompetitive binds only when the substrate is bound and it binds to additional binding site on active site
Noncompetitive binds only to allosteric site and in all conditions (so when substrate is bound and when it is not)
When does the uncompetitive inhibitor bind?
Only after substrate is bound
When does the noncompetitive inhibitor bind?
In all conditions, substrat bound or not bound
What does sulphanilamide mimic the structure of? and thus inhibits the metabolisation of
PABA (p-aminobenzoic acid)
How is the rate of reaction effected by the inhibitor?
The rate decreases
Due to decrease in affinity
More substrate is needed
What is Km?
Substrate concentration at half Vmax
What happens to the Vmax during competitive inhibition?
Nothing
It is not changing because as substrate increases inhibition decreases eventually to the point where it disappears
What happens to the Km during competitive inhibition?
Increases
Does competitive inhibition affect catalysis?
No, does not effect the catalysis and the process
With competitive inhibitors how do the Vmax compare to reaction with no inhibitor?
They are the same
In a noncompetitive inhibitor how is the Km effected?
No change
Because the binding site is the same and the binding is the same (affinity for binding is the same)
In a noncompetitive inhibitor how is the Vmax effected?
Decrease
Activity of enzyme is decreased
What does the noncompetitive inhibitor affect? The affinity to bind or the enzymatic activity?
Enzymatic activity
Can a change in conformation cause and enzyme to have affinity for a different substrate?
Yes
Which inhibitor can be used to map an active site?
Irreversible inhibitor
Affinity labels
3 major types of irreversible inhibitors
Group specific reagents
Affinity labels (or reactive substrate analogs)
Suicide inhibitors (or mechanism-based inhibitors)
Why is it group specific reagents irreversible inhibition?
Only interacts with one specific amino acid in a specific position in the compound (the ex serine of the active site)
How does the affinity labelling irreversible inhibitor work?
Part of inhibitors attaches to part of the enzyme
How does the suicide irreversible inhibitor work?
Binds as a substrate and is then modified by enzyme into an irreversible inhibitor
What kind of inhibitor is penicillin?
Suicide irreversibel inhibitor
What are transition state inhibitors?
Inhibitor that resembles the transition state substrate
What are enzyme inhibitors?
Compounds that decrease an enzyme’s activity
What are competitive inhibitors?
Inhibitors that bind to the active site
What is noncompetitive inhibition?
Inhibitors that bind to a different part of the enzyme than the active site
How does a competitive inhibitor change the Vmax?
No change
How does a competitive inhibitor change the Km?
Increase
How does a noncompetitive inhibitor change the Vmax?
Decrease
How does a noncompetitive inhibitor change the Km?
No change
What kind of bond does irreversible inhibitors form with the active site?
Covalent bond
How can you displace the reversible inhibitors?
By increasing the amount of substrates
2 most common types of inhibitors
Competitive
Uncompetitive
Example of competitive inhibitor drug
Sulfanilamide
What does methotrexate inhibit?
DNA synthesis
Where does the lineweaver-burk plot of a competitive inhibitor intersect with that one no inhibitor?
At the y axis
What does a non competitive inhibitor effect, the enzyme activity or the ability to bind?
The enzyme activity
Where does the lineweaver-burk plot of a noncompetitive inhibitor intersect with that one no inhibitor?
At the x-axis
What can irreversible inhibitors be used to map?
The active site
How does suicide inhibitors work?
They bind to the enzyme as a substrate and when catalysis occur they are modified into an irreversible inhibitor
What does penicillin do?
Irreversibly inactivate a key enzyme in bacterial cell-wall synthesis
What is the reactive site of penicillin?
The peptide bond of its beta-lactam ring
Does uncompetitive inhibitors have affinity for free enzymes?
Very little
What does uncompetitive inhibitors mainly bind to
Enzyme-substrate complex
What is mixed inhibition?
When the inhibitor can bind both to the free enzyme and the enzyme-substrate complex
How does a mixed competitive inhibitor change the Vmax?
Decreases
How does a mixed competitive inhibitor change the Km?
No change
What does penicillin bind to?
Transpeptidase
What kind of inhibitor is penicillin?
Suicide inhibitor
