Biology Made Easy: How Reversible Enzyme Inhibitors Work

Posted by Eden on 8/14/17 6:04 PM


Inhibitors play an important role in regulating enzyme function. In this review, we will cover three broad categories of reversible enzyme inhibitors and discuss their impact on two important statistics related to enzyme function: the maximum velocity (VMAX.pngof an enzyme and the Michaelis constant (KM.png) of an enzyme.

To start, lets define VMAX.pngandKM.png.VMAX.pngis the maximum rate at which a reaction will occur. You can think of it as the rate of the reaction when there is enough substrate present that there is substrate in every enzyme’s active site.  

KM.pngis a measure of the enzyme’s affinity for the substrate. More specifically,KM.pngrefers to the substrate concentration at which half of the enzyme’s active sites contain substrate. You can also think of it as the concentration of substrate required for the enzyme to function at 50% of VMAX.png. When the KM.pngis high the enzyme has lower affinity for the substrate (more substrate must be present for half of the active sites to be filled) and vice versa.

Now that we have those definitions out of the way, we can talk about how different kinds of inhibition impact those two important numbers.

Competitive inhibition

In competitive inhibition, an inhibitor binds to the enzyme, making it impossible for the substrate to bind at the active site.

This could happen in one of two ways:

1) The inhibitor could bind at the active site, blocking the substrate from accessing it

2) In the case of allosteric competitive inhibition, if the active site is empty the inhibitor could bind at an allosteric site (any site other than the active site) which would induce a change in the empty active site that would block the substrate from binding there.

Regardless of which kind of competitive inhibition is occurring, the substrate and the inhibitor are directly competing for the enzyme. In other words, whichever molecule (substrate or inhibitor) gets to the enzyme first, gets to use the enzyme.

As a result, increasing the amount of substrate present can overcome this kind of inhibition because it increases the likelihood that the substrate will come in contact with the enzyme prior to the inhibitor coming in contact with the enzyme. In other words, increasing substrate concentration allows the substrate to outcompete the inhibitor.

How does this impactVMAX.png and KM.png?

VMAX.pngdoes not change because enough substrate can always outcompete the inhibitor to achieve the original VMAX.png.

Competitive inhibition increases KM.pngbecause the substrate concentration has to be higher to outcompete the inhibitor and fill half of the enzymes’ active sites.  

Noncompetitive inhibition

The inhibitor prevents the enzyme from catalyzing the reaction by binding to an allosteric site whether or not the substrate is in the active site.

The binding of the inhibitor changes the shape of the active site such that the reaction can no longer be catalyzed.

This is different from competitive inhibition because the inhibitor can bind to the enzyme and stop the reaction, even if the substrate is already bound to the active site. As a result, it no longer matters “who got there first.” This means that you cannot overcome noncompetitive inhibition by simply increasing the amount of substrate present.

How does this impact VMAX.png&KM.png?

Noncompetitive inhibition decreases VMAX.pngbecause no matter how much substrate is present, some of the enzymes will always be prevented from catalyzing the reaction by the inhibitor. The means that the enzyme can never reach its original VMAX.png.

Noncompetitive inhibition does not change KM.pngbecause affinity for the enzyme is unchanged, there are just fewer functioning enzymes. 

Uncompetitive inhibition

In uncompetitive inhibition, the inhibitor can only bind to the enzyme substrate complex (not the enzyme alone) and it prevents the product from forming and being released

Like with noncompetitive inhibition, this kind of inhibition cannot be overcome by increasing substrate concentration, because high substrate concentrations cannot outcompete uncompetitive inhibitors.

How does this impactVMAX.png & KM.png?
  • Uncompetitive inhibition decreases VMAX.png because when the inhibitor binds to the enzyme substrate complex it prevents the enzyme from catalyzing the reaction and forming product. Adding additional substrate will not outcompete the inhibitor in this case so VMAX.png decreases.
  • Uncompetitive inhibition decreases KM.png. This is because the binding of the inhibitor to the enzyme-substrate complexes to form enzyme-substrate-inhibitor complexes leads to a net loss of enzyme-substrate complexes. This loss causes an equilibrium shift that favors the binding of the enzyme to the substrate so the enzyme’s affinity for the substrate increases. Here is a drawing of the relevant equilibrium to help you think this through:
Eden Blog.png

If you aren’t yet familiar with equilibriums, feel free to simply memorize this last fact or you can check out this short video for more information. 

I hope this review helped you master the biochemistry behind enzyme inhibitors-happy studying!

Are you interested in connecting with a biology tutor in Boston, New York, or online?

Contact Us!

Want to read more on the subject?

What is CRISPR-Cas9?

What is the phospholipid bilayer and what determines its fluidity?

An Introduction to Blood Types: Genotype, Phenotype, Inheritance, Transfusion, and More!

Tags: biology