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Noncompetitive inhibition
Seeing how a noncompetitive inhibitor can bind whether or not the substrate is bound, and vice versa.
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Im having trouble understanding the difference between the allosteric competitive inhibition and the noncompetitive inhibition. I've been taught the same thing - that the allosteric competitive inhibition IS the noncompetitive inhibition. So the inhibitor changes the conformation of the protein when it bonds to the allosteric site, but does the inhibitor also change the conformation when it is noncompetitive? I mean how can both inhibitor and substrate bind and still nothing happens? Does the conformation change somewhere else on the enzyme or is the inhibitor of another kind?(23 votes)
1. Allosteric competitive:
i: enzyme + inhibitor -/-> no reaction because enzyme changes conformation
ii: enzyme + substrate -> reaction takes place until the enzyme gets changed when an inhibitor successfully competed (1.i:) against the binding of a substrate and is attached to the enzyme.
2. Noncompetitive:
i: substrate + inhibitor + enzyme -> no reaction, inhibitor and substrate are both present at their "needed" sites but since the inhibitor changes the activity of the enzyme, the substrate is not reacting.(24 votes)
I am confused because what this video tells me is slightly different than what other sources are saying. In my Kaplan MCAT book, it says "Once the enzyme's conformation is altered, no amount of extra substrate will be conducive to forming an enzyme-substrate complex". Wikipedia says "It changes the conformation of an enzyme as well as its active site, which makes the substrate unable to bind to the enzyme effectively so that the efficiency decreases". However, in this video, Sal repeatedly said that the substrate is able to bind to the active site even in the presence of an inhibitor, it's just that the reaction will not proceed. I just wanted to get this clarified so that I can make sense of the fact that Km doesn't change. This is consistent with what Sal says, but not Wikipedia or Kaplan. Are they just wrong then?(6 votes)
Do not confuse it with allosteric inhibition.
What you described is allosteric inhibition.
So, in allosteric inhibition - enzyme, therefore active site, is deformed and unable to bind substrate.
Noncompetitive inhibition - is also binding of the inhibitor to another site (no the active site), and also preventing the reaction from occurring, but this is reversible. What does it mean? It means that after binding of inhibitor, an active site does not change, but ti just prevents a reaction from happening. In the case of inhibitor dissociates, the enzyme is functioning again.
The allosteric inhibitor is a permanent change, while this is a temporary change.(6 votes)
what is the point of both the substrate and the inhibitor binding to an enzyme, when the reaction isnt even going to occur?(6 votes)
But the reaction, i.e. the binding between enzyme and either substrate or inhibitor, will occur if you have the correct enzyme and either substrate or inhibitor. The Inhibitor will simply prevent the protein from completing its function.(5 votes)
Is the allosteric site just a spot on the enzyme adjacent to the active site or is it another intended bonding place like the active site.(7 votes)
What would happen if the designated substrate arrives at the active site first, and while the reaction is going on, the inhibitor binds to the enzyme? Would the reaction proceed or would it stop?(3 votes)- If you are talking about non-competitive inhibition, the reaction would not proceed, because the inhibitor would make it not proceed. If you are talking about competitive inhibition, and the substrate got there first, the inhibitor would not be able to bind. Hope this helps:)(5 votes)
At3:13, why does Sal say "and maybe this guy leaves as well" when he refers to the non-competitive inhibitor? Is it because the non-competitive inhibitor can also stay attached to the enzyme?(3 votes)- Exactly. That is why it is called * non-competitive*.
It could stay attached to an enzyme or not, but not occupying the active site.(5 votes)
what is the function of an inhibitor in a living cell? could you give me example of inhibitor and their targeted enzyme?(3 votes)
One class of examples occurs where one or more products of a pathway inhibit enzymes at the start of the pathway.
This is known as product inhibition and is a form of negative feedback.
A classic example of this is in glycolysis where ATP acts as an allosteric (non-competitive) inhibitor of phosphofructokinase.
You can learn more about this here:
https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/variations-on-cellular-respiration/a/regulation-of-cellular-respiration(4 votes)
- my fellow students, keep in mind that binding doesn't necessarily mean that reaction will occur, as active center contains not only binding site (which primarily holds substrate in place), but other structures too, which actually catalyze the reaction (I suppose exactly these structures are changed by non-competitive inhibitors).(3 votes)
- A noncompetitive inhibitor can bind on the active site? I thought that it binds anywhere else but the active site.(3 votes)
Can the substrate begin to catalyze before the inhibitor binds? What happens then? Does it just stop the reaction?(2 votes)- First, the substrate cannot catalyze, the enzyme is the one who catalyzes the reaction and converts the substrate into product.
If reaction starts before inhibitor binds, yes, you are correct. Inhibitor just stops the reaction.(3 votes)
3:13Video transcript
- [Voiceover] In the video
on competitive inhibition, we saw that competitive inhibition
is all about a substrate or a potential substrate,
an inhibitor competing for the enzyme. And whoever gets there
first, gets the enzyme. If the inhibitor gets there first, then the substrate isn't able to bind, and of course no reaction is catalyzed. If the substrate is
able to get there first, then the inhibitor isn't able to bind, and the reaction does get catalyzed. Now the inhibitor and the substrate, they both might compete
for the active site, if we're talking about
competitive inhibition. But you also have allosteric
competitive inhibition. Where they're still trying
to compete for the enzyme, whoever gets there first, gets the enzyme. But the inhibitor doesn't necessarily bind at the active site, they
bind at an allosteric site. But it's the same idea. If the inhibitor gets
to the allosteric site before the substrate
gets to the active site, then the confirmation
of the protein changes, so that the active site, you
know it changes a little bit, something like let me
draw in that same color, the confirmation of the
protein changes a little bit. And then the actual intended
substrate isn't able to bind. If the intended substrate binds, then that changes the
confirmation a little bit at the allosteric site,
and then the inhibitor isn't able to bind. So if that's competitive
inhibition, where there's like who gets to the enzyme first, what is non-competitive
inhibition all about? Well let's draw that. So, non-competitive inhibition. So, non-competitive inhibition. And the big picture here is that they can both bind. Whether one binds to the
enzyme doesn't affect whether the other binds. So let's talk about it a little bit. So, this is my enzyme. That's my enzyme, right over there. And what we have happening, of course, is if the substrate's able
to get to the active site, then of course the reaction
is going to be catalyzed. And we saw that up here. Substrate binds to the active site, and then the reaction is catalyzed, in this case the substrate got broken up into two other molecules. But in non-competitive inhibition, what happens is a substrate can bind, and so can an inhibitor. And the inhibitor can bind
at an allosteric site, so this is our inhibitor right over here. The inhibitor can bind
at an allosteric site, and when they're both bound, notice they're not
competing for the enzyme, they both can be on the enzyme. This character can bind
to the enzyme whether or not the substrate is there. But if this guy binds to the enzyme, the substrate can still
bind to the enzyme, but now the reaction
isn't going to proceed. So now the reaction is
going to look like this: so now there's not going to be a reaction. If this happens, the only
option is that they both unbind. So now this character is just going to leave the active site. No reaction has been catalyzed. So, it just prevented
anything from happening. And maybe this guy leaves as well. And the way I showed this
non-competitive inhibition, I showed it happening
at an allosteric site, the inhibitor attaching
at an allosteric site, but it actually doesn't even
have to be the same case as long as it does not prevent, it can actually bind close
to or even at the active site as long as it does not
prevent the substrate from binding to the active site. So you can even have
a situation like this: this is the one that's typically given for non-competitive
inhibition where you have the inhibitor binding
at an allosteric site, but the idea here is that both of them can bind to the enzyme. If one of them binds first, then the other one can still bind. If the substrate binds first, then the inhibitor can still bind. If the inhibitor binds first, then the substrate can still bind. But, the reaction is not
going to be catalyzed. But you can even have a situation where the inhibitor and the substrate can both bind in or
around the active site. So that's the inhibitor, and
then this is our substrate, this is the substrate. But once again, this reaction
is not going to occur. We have non-competitive inhibition. They're not competing for the thing, they can both bind to
it, whether they can bind isn't dependent on whether
the other one is bound, but if the inhibitor is there
then it's not going to allow the reaction to actually be catalyzed. As opposed to competitive inhibition, whoever gets to the enzyme first, gets the enzyme. Hopefully that clarifies things.