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?(21 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.
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:)(4 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?(2 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.(4 votes)
- In non-competitive inhibition, when both the substrate and the inhibitor bind to the enzyme, why does that stop the reaction proceeding? I don't think the inhibitor can have changed the shape of the enzyme, as otherwise surely the substrate wouldn't be able to bind?(2 votes)
- Once an enzyme binds to a substrate molecule it sometimes needs to flex a little to catalyze the reaction. You can think of a non-competitive inhibitor as interfering with that flexing while still allowing binding.
See for example the figure from this wikipedia article :
- After the Non-Competitive Inhibition happens, and both the substrate and the inhibitor are forced to break their bind to the enzyme, do they continue trying to bind to the enzyme until one or both get catalyzed separately?(2 votes)
- It depends. If they are forced to dissociate from an enzyme, then I suppose they won't compete again to bind to the same enzyme unless you 'force' them again to bind (put them in close proximity to active site).(2 votes)
- Why Vmax is lower in non competitive inhibition?(2 votes)
- When an enzyme is bound by a non-competitive inhibitor the enzyme is no longer able to act as a catalyst. This is just like the enzyme is no longer there. Since the reaction rate§ is proportional to the amount of enzyme and there is now effectively less enzyme, the reaction rate goes down.
§Vmax is the maximum reaction rate — i.e. when all of the enzyme is fully occupied with substrate.(2 votes)
- In the last example, is the inhibitor binding to the ES complex? Would this also be called uncompetitive inhibition.(2 votes)
- [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.