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7. Enzyme Inhibition and Regulation

1

Sequential (KNF) Model

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So now that we've covered the concerted model in this video, we're going to introduce the second model that explains the sigmoid all kinetics of Alice Derek Enzymes. And that second model is the sequential model. And so the sequential model is also sometimes referred to as the K N F model. And again, K N F is just the abbreviations of the last names of the three scientists that discovered the sequential model. And so, it turns out again that it's more commonly referred to as just the sequential model than the K N F model. And so, for that reason, moving forward in our course, I'm mainly going to be referring to it as just the sequential model. And so when it comes to the sequential model, unlike the concerted model and Alice Derek Enzymes, sub units will actually undergo sequential conversions from the T state to the our state. And so what this means is that the sub units of analysis, Eric Enzyme, they do not simultaneously convert from t state, tow our state. Instead, the sub units will convert from the T state, tow our state independently of one another, and this is because the T state tow. Our state conversions are actually induced via the substrate binding. So it occurs via the induced fit model. And so, ultimately, again, what this means is that the sub units of analysis Eric Enzyme, can be present in different states, which means that hybrids are indeed allowed, which is again very, very different from the concerted model where hybrids are not allowed. And so, in other words, pretty much what we're saying is that with the sequential model T state tow, our state transitions do not necessarily encompass the entire Alice Derek enzyme. Instead, the T state and our state transitions occur within each sub unit of the Alice Derek enzyme sequentially. And so if we take a look down below at our image notice. What we're saying is that when it comes to the sequential model or the K n F model, the transition from the Alice Terek enzyme, where all of its sub units are in the T state to the Alice Derek Enzyme, where all of the sub units are in the our state, is going to occur sequentially with each sub unit. And so what this means is that it's possible for one sub unit to be in the Our state, whereas the other three sub units are in the T state and it's pretty much possible for every combination that you can think of. And so that's again because the transitions from T state to our state occur sequentially, with each sub unit allowing for all of these hybrids that we see here and again, this is very, very different from the concerted model. So now that we understand the basics of the sequential model and our next lesson video, we're going to talk about how the sequential model actually explains positive and negative cooperative ity and therefore can explain the sigmoid all kinetics of Alice Derek Enzyme. So I'll see you guys in our next video.

2

Sequential (KNF) Model

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So now that we know the basics of the sequential model and this video, we're going to talk about how the sequential model allows for both positive and negative cooperative ity. And that's actually very different than the concerted model. And so, unlike the concerted model, which Onley allows for positive cooperative ity again, the sequential model allows for both positive and negative cooperative ity. And so when it comes to cooperative ity, this is just describing the idea that substrate binding toe one of the sub units of analysis, Eric Enzyme, actually increases the likelihood that neighboring sub units are going to take on either the T state or the our state confirmation. And so, as we already know from our previous lesson videos positive cooperative. ITI is essentially the idea that binding of the substrate to an analyst, Eric Enzyme, actually makes it easier for other Alice Terek enzyme subunits toa bind the substrate to And so here we're saying that positive cooperative ITI is just this idea that binding of the substrate, uh, to ah sub unit of analysis, Eric Enzyme actually promotes neighboring sub units to take on the our state, which is the relaxed state and bind substrates mawr efficiently. And so, of course, negative cooperative. It is going to be the exact opposite of positive cooperative ity. And so negative cooperative. He says that binding of the substrate to an Alice Derek enzyme sub unit actually makes it harder for other Alice Derek enzyme sub units to bind the substrate. And so here we're saying that negative cooperative ITI is just this idea that binding of the substrate molecule to an Alice Derek enzyme sub unit will actually promote neighboring Alice Derek enzyme sub units to take on the T State, which is the 10th state, and bind, bind, substrates inefficiently and so down below. In our example, we're going to distinguish the positive and negative cooperative ity of the sequential model. And so notice at the top left right here. Essentially, we're showing you an image that represents positive cooperative ity of the sequential model. And so, of course, on the far left here, what we have is the Alice Derek enzyme with all four sub units and the T state. And when it comes to the sequential model, we know that when it converts from the T state to all four subunits in the our state, the sub units are going to sequentially convert. And that is because the substrate is actually going to induce the each individual sub unit to convert from the T state to the our state. And so here we have some substrate binding to the top left sub unit converting it from the T state to the our state and noticed that with positive cooperative ity, once substrate is bound to that one sub unit with er state, it is going to influence or promote the neighboring subunits toa also take on the our state and so notice that, uh, this our our state sub unit promotes the these two neighboring sub units, uh, to take on a state where it has an increased substrate binding affinity making them more likely, uh, increasing the likelihood that these neighboring sub units are gonna take on the our state. And so notice that as soon as we add more substrate, we have these subunits here binding on converting to the our state. And then, of course, now this sub unit is being promoted eso that it increases its likelihood to bind substrate and then, of course, as soon as we add substrate and it becomes available. All of these subunits are going to quickly, uh, bind substrate and, uh, be in this our state. And so notice that positive cooperative ity here on this enzyme kinetics plot on the right corresponds with this green curve. And we already know that positive cooperative ity allows for the sigmoid all kinetics that we see with Alice Terek enzymes, and so weaken label this green curve Aziz showing positive cooperative ity. Now notice that the black curve here represents the curve where there is absolutely no cooperative ity. And we know that it's actually Mikhail's meant in enzymes that do not have any cooperative ity because cooperative iti is really just a feature of Alice Derek Enzymes. And so here, with the no cooperative he noticed that it resembles a rectangular hyperba just like Nicholas Mint and enzymes. Now, when it comes to negative cooperative ity again, this is going to be the opposite of positive cooperative ity. And so, with the sequential model again, on the far left, we have the Alice Derek enzyme in all, um, for sub units are in the T state. And then, of course, uh, each sub unit is going to sequentially convert from the T state to the our state. But notice here that upon substrate binding to this sub unit up here, it does convert to the our state but with negative cooperative ity. It actually promotes the neighboring sub units to take on the T state and inefficient binding. And so notice that with the substrate bound to the sub unit, the neighboring sub units here take on this decreased substrate binding affinity. And so, as we ADM or Substrate, this sub unit here combined some substrate. But again, these two sub units still have the decreased substrate binding affinity. And so, in order to get these substrates Thio essentially bind. Um, in order to get these subunits toa bind substrate, we have Thio increase the substrate concentration by ah lot in order to get this sub unit here toe bind substrate And then, of course, if we want this sub unit to bind substrate, we're gonna have to increase the substrate concentration Ah, lot Mawr as well. And so ultimately, what this leads to is having a curve that looks like this blue one right here, and so notice that it takes quite a lot of substrate concentration in order to get this curve all the way up to the V max. And so that is a feature of negative cooperative ity. And so, uh, some Alice Terek enzymes actually do, uh, show some negative cooperative ity. And so the sequential model is, um, essentially a model that allows for both positive and negative cooperative ity. And so, for Alice Derek enzymes that display negative cooperative ity, it's the sequential model. That would be a better, better model. However, if positive cooperative ITI is displayed, then either the concerted or the sequential model could explain the positive cooperative ity that we see. And so, in our next lesson video, we're going to directly compare on compare and contrast the concerted as well as the sequential model. And so this here concludes our lesson on how the sequential model allows for both positive and negative cooperative ity. And so I'll see you guys in our next video

3

Problem

True or False: Most allosteric enzymes behave according to the concerted model, not the sequential model.

A

True.

B

False.

4

Sequential (KNF) Model

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in this video, we're going to compare and contrast what we already know about the concerted and sequential models. And so even though in our previous lesson videos, we talked about these two models as if they were completely separate models. It turns out that most Alice Derek Enzymes actually behave according to some combination of both of these models, essentially a combination of the concerted and sequential models, which means that it's really important for us to understand the unique features that each of these models brings to the table and noticed down below. We actually have a table, and on the left hand side we have the concerted model, whereas on the right hand side we have the sequential model and so recall from our previous lesson videos that sometimes the conservative model is referred to as just the MWC model, and sometimes the sequential model is referred to as just the K and F model. Now recall that the unique feature of the concerted model is actually this word concerted, which we know from our previous organic chemistry courses, means jointly happening all together at the same time. Essentially, it means simultaneously, and so we already know that with the concerted model, the T state to our state conversions occur simultaneously and all of the sub units of the Alice Derek enzyme so that the T state our state conversions, encompass the entire Alice Derek enzyme as a whole, so that all of the sub units are always going to be in the same exact state. Now, this is not the case with the sequential model, and that's because the T state to our state conversions do not encompass the entire Alice Derek enzyme. Instead, these t state our state conversions occur sequentially and each of the sub units of the Alice Derek enzyme independently of one another. Now, with the concerted model, the T state to our state conversions do not require any substrate whatsoever. So over here you can see that the T state to the our state conversions will occur even in the absence of substrate, where that is not the case with the sequential model. And that's because with the sequential model, the T state to our state conversions, Onley occur via substrate binding in the induced fit model. And so over here you can see that the T state to the our state conversion is going to occur independently in each of the individual sub units sequentially via substrate binding to that particular sub unit. And this means that hybrids are definitely going to be allowed with the sequential model, as indicated in our table. But of course, we know that with concerted model, absolutely no hybrids are allowed whatsoever. And we also know that the concerted model does explain the sigmoid all kinetics of Alice Derek Enzymes, which means that it does allow for positive cooperative ity. But recall that it on Lea allows for positive cooperative ity, and it does not allow for negative cooperative ity, whereas with the sequential model, it actually allows for both positive and negative cooperative ity. And so this year concludes our comparing contrast of the conservative model in the sequential model, and we'll be able to get some practice utilizing these concepts as we move forward in our course. So I'll see you guys in our next lesson. Video

5

Problem

The Sequential model for allosteric enzyme behavior:

A

Cannot account for the reactions that display negative cooperativity.

B

Postulates binding of substrates & inhibitors by the induced-fit model.

C

Requires that the conformation of all subunits change simultaneously.

D

Is conceptually and mathematically simpler than the concerted model.

6

Problem

Which of the following best describes negative cooperativity?

A

Binding of one substrate molecule stimulates binding of a second substrate.

B

Binding of one substrate molecule inhibits binding of a second substrate.

C

Binding of one substrate molecule leads to negative reaction rates.

D

Binding of one substrate molecule causes a negative effect/result in the cell.

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