Noncompetitive vs allosteric inhibition: what's the difference?

[FeralisExtremum]

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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[aqz]

Mmm pictures good. pictures nice.

Made things clearer, wish everything could be learned through simple visuals like these.

 

[FeralisExtremum]

A lot of things, at least in biology, probably could. I think visual, interactive learning software will probably be the future of education.

 

[hasanein4u]

Thank you

 

[Incis0r]

Another example of allosteric competitive inhibition below:

Is the quoted example above allosteric competitive inhibition solely because of the conformational change in the enzyme which prevents the substrate from binding? What if the substrate could bind (as in your first example) but the reaction could not proceed- that would make it allosteric noncompetitive inhibition right?

So, just to make sure I'm taking away the right lesson here:
Allosteric inhibition = all cases where the enzyme is inhibited minus standard nonallosteric competitive inhibition
Allosteric competitive inhibition = when the inhibitor binds to the allosteric site in such a way that it either a) causes a conformational change that prevents the substrate from binding to its active site or b) parts of the inhibitor directly prevent the substrate from binding to the active site by coming in the substrate's way
Allosteric noncompetitive inhibition = when the inhibitor binds to the allosteric site, and does not cause a change in active site conformation, so the substrate can bind as well, but the reaction cannot proceed while the inhibitor is in the site, for one reason or another?

Thank you Feralis!

 

[FeralisExtremum]

Is the quoted example above allosteric competitive inhibition solely because of the conformational change in the enzyme which prevents the substrate from binding? What if the substrate could bind (as in your first example) but the reaction could not proceed- that would make it allosteric noncompetitive inhibition right?

Correct on both counts!

So, just to make sure I'm taking away the right lesson here:
Allosteric inhibition = all cases where the enzyme is inhibited minus standard nonallosteric competitive inhibition -assuming the inhibition is from an inhibitor binding to an allosteric site, yes
Allosteric competitive inhibition = when the inhibitor binds to the allosteric site in such a way that it either a) causes a conformational change that prevents the substrate from binding to its active site or b) parts of the inhibitor directly prevent the substrate from binding to the active site by coming in the substrate's way -correct, if the substrate cannot bind as a result of the allosteric inhibitor then it is allosteric competitive
Allosteric noncompetitive inhibition = when the inhibitor binds to the allosteric site, and does not cause a change in active site conformation, so the substrate can bind as well, but the reaction cannot proceed while the inhibitor is in the site, for one reason or another? -correct

Thank you Feralis!

See my comments in bold above

 

[massap24]

I was just reading this on your notes and couldn't figure out the difference. This helped me out a lot thanks