How are enzyme inhibitors related to pharmacology?
Many drugs work as enzyme inhibitors
Many types of inhibitors see Enzyme inhibitor
- Most important ones
- Competitive inhibitors
- Non-competitive inhibitors
Basic enzyme function
The two enzyme inhibitor types block the catalysis of the enzymatic reaction in different ways resulting in different properties
- A competitive inhibitor “competes” for the same binding site where the substrate is normally bound. Thus, the substrate is blocked from binding and being catalyzed by the enzyme
In case of a high substrate concentration (high [S]) this can be overcome (for reversible competitive inhibitors)
A non-competitive inhibitor binds in a different binding site (not the one of the substrate) and it changes the 3-Dimensional shape of the enzyme in a way that blocks the substrate from binding to its binding site
- A high substrate concentration (high [S]) can not overcome this and thus
- Enzymes affected by non-competitive inhibitors are practically absent
How do the different types of inhibitors affect the respective Michaelis-Mentent plots?
Normal Michaelis-Mendel plot
Competitive inhibitor
Michaelis-Mendel plot for competitive inhibitor
- KM becomes higher
- If you add more substrate, eventually you will reach Vmax but it is “more difficult” to get there
- Vmax does not change
Non-competitive inhibitor
Michaelis-Mendel plot for non-competitive Inhibitor
- Vmax becomes lower
- Essentially, it is like the enzymes affected are “removed” from the system and, thus, you will never reach the initial Vmax but the new Vmax is relative to the remaining-uninhibited enzymes
- Vmax/2 is decreased as well
- KM does not change
How do inhibitors change the Lineweaver Burk Plot?
Initial Lineweaver Burk Plot
Competitive inhibitor
- Remember from the previous graphs that Vmax stays the same so the line “turns around” that point (1/Vmax)
- Also remember that KM goes up. Since in the diagram above it is a denominator, an increase in KM-s value will result in the fraction getting closer to zero, so the line “moves” counterclockwise
Non-competitive inhibitor
- Remember from the previous graphs that the KM does not change in an acting non-competitive inhibitor, so this is going to be the point that stays the same and the line “turns around” it (-1/KM)
- Since Vmax is affected negatevly, a fraction with Vmax as a denominator will increase in value. Thus, the line moves counterclowise around (-1/KM)
Recap
Competitive
- Binds to active site of S => S can’t get to binding site => More S antagonizes the inhibitor
- => KM increases | Vmax stays the same
- Inhibitor has similarity with S
Non-competitive
- Binds to differnet site => Changes shape => Non-functional binding site
- => Vmax decreases | KM stays the same
- Unaffected by more S
- Not similar to S