Noncompetitive vs allosteric inhibition: what's the difference?

[FeralisExtremum]

Hey guys, I made this post over in the DAT section but I thought I would put it here as well since the same concepts are found on the MCAT:

This isn't actually a question of mine, but an answer to a question I have seen many times and often had trouble with. Here is a (lengthy) writeup with images that I believe will clear everything up:

A noncompetitive inhibitor is defined as: "a substance that inhibits the action of an enzyme by binding to the enzyme at a location other than the active site."

Allosteric inhibition is defined as: "a substance that binds to the enzyme and induces the enzyme's inactive form."

These definitions appear extremely similar, so what is the difference, and why do we distinguish between these two concepts? The following is an illustrated example of noncompetitive inhibition:

Note that it does NOT prevent the substrate from binding to the active site, but it still prevents the reaction from completing. Also note that the noncompetitive inhibitor binds at an allosteric site. This is key to understanding the difference: all noncompetitive inhibition is allosteric inhibition, but not all allosteric inhibition is noncompetitive inhibition. Why? Because certain forms of allosteric inhibition can prevent the substrate from binding to the active site, in others words, allosteric inhibition can be noncompetitive or competitive. The above picture is an example of allosteric noncompetitive inhibition. Below is an example of allosteric competitive inhibition:

Another example of allosteric competitive inhibition below:

For contrast, here is standard (non-allosteric) competitive inhibition:

With this in mind, we can now understand why “allosteric inhibition” is a broad concept that does not follow specific Vmax or Km trends like ‘standard’ competitive and noncompetitive inhibition do, because it can refer to a variety of conditions under which the substrate may or may not be able to bind to the active site.

It is also worth noting that if you use Barron's AP Biology review book, as of the 3rd edition, it has a completely incorrect definition of noncompetitive inhibitors.

Please let me know if this helped you out, or if I can make it any clearer.

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[Mornhavon]

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[FeralisExtremum]

Yes, but it helps to be more specific. In competitive the substrate and inhibitor bind at the same active site - pretty straightforward.

In allosteric regulation (speaking specifically about inhibition here), the inhibitor is binding at a site other than the active site, and changing the enzyme in some way to make it inactive. This can refer to a number of different types of inhibition: allosteric competive (inhibitor binding to the allosteric site stops the substrate from binding) or allosteric noncompetitive (inhibitor binds to allosteric site, substrate can still bind but enzyme cannot catalyze reaction).

You'll notice noncompetitive inhibition IS allosteric regulation, but only one specific type of it. It helps to know whether or not the substrate is still binding to the active site or not because that lets you predict how/if the Km and Vmax change in the presence of an inhibitor.

 

[Intellex]

Great explanation

 

[sciencebooks]

This was WAY helpful! Thanks!

 

[Chunkle]

This is a good way to think about it. EK Bio explains it like this as well.

Competitive actively competes for the active site of the enzyme, so Vmax stays the same, all you need to do is add more substrate and it can out compete the inhibitor.

Allosteric binds on an alternative site as to actually change the conformation of the enzyme, in this case, Vmax will actually change. If it is a noncompetitive inhibitor, the Vmax will lower, and no matter how much substrate you add, it will stayed lowered, while allosteric binding can actually change the conformation as to actually increase Vmax as well.

 

[osujic1]

all of the images are gone

 

[osujic1]

Hey guys, I made this post over in the DAT section but I thought I would put it here as well since the same concepts are found on the MCAT:

This isn't actually a question of mine, but an answer to a question I have seen many times and often had trouble with. Here is a (lengthy) writeup with images that I believe will clear everything up:

A noncompetitive inhibitor is defined as: "a substance that inhibits the action of an enzyme by binding to the enzyme at a location other than the active site."

Allosteric inhibition is defined as: "a substance that binds to the enzyme and induces the enzyme's inactive form."

These definitions appear extremely similar, so what is the difference, and why do we distinguish between these two concepts? The following is an illustrated example of noncompetitive inhibition:

Note that it does NOT prevent the substrate from binding to the active site, but it still prevents the reaction from completing. Also note that the noncompetitive inhibitor binds at an allosteric site. This is key to understanding the difference: all noncompetitive inhibition is allosteric inhibition, but not all allosteric inhibition is noncompetitive inhibition. Why? Because certain forms of allosteric inhibition can prevent the substrate from binding to the active site, in others words, allosteric inhibition can be noncompetitive or competitive. The above picture is an example of allosteric noncompetitive inhibition. Below is an example of allosteric competitive inhibition:

Another example of allosteric competitive inhibition below:

For contrast, here is standard (non-allosteric) competitive inhibition:

With this in mind, we can now understand why “allosteric inhibition” is a broad concept that does not follow specific Vmax or Km trends like ‘standard’ competitive and noncompetitive inhibition do, because it can refer to a variety of conditions under which the substrate may or may not be able to bind to the active site.

It is also worth noting that if you use Barron's AP Biology review book, as of the 3rd edition, it has a completely incorrect definition of noncompetitive inhibitors.

Please let me know if this helped you out, or if I can make it any clearer.

 

[FeralisExtremum]

That's what I get for not using an image host. I think I have a copy of the images elsewhere but it will be a while before I get a chance to re-post them.