Ben Papadakis
Benjamin Papadakis

Benjamin Papadakis

Pharmacology Fundamentals: Understanding Enzyme Kinetics

Pharmacology Fundamentals: Understanding Enzyme Kinetics

Ben Papadakis's photo
Ben Papadakis
·Apr 18, 2022·

3 min read

  • Many drugs work as enzyme inhibitors

  • Many types of inhibitors see Enzyme inhibitor

  • Most important ones
    • Competitive inhibitors
    • Non-competitive inhibitors

Basic enzyme function

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The two enzyme inhibitor types block the catalysis of the enzymatic reaction in different ways resulting in different properties

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  • 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?

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Normal Michaelis-Mendel plot

Competitive inhibitor

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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

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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?

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Initial Lineweaver Burk Plot

Competitive inhibitor

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  • 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

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  • 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
 
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