Concerted (MWC) Model - Video Tutorials & Practice Problems
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Concerted (MWC) Model
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So now that we've covered allosteric effectors, in this video, we're going to introduce the first model that explains positive cooperativity and the sigmoidal kinetics of allosteric enzymes, and that first model is the concerted model. And so the concerted model is also sometimes referred to as just the MWC model, and MWC is just the abbreviations of the last names of the 3 scientists that discovered the concerted model. But what I found is that this model is more commonly referred to as just the concerted model than the MWC model, and so moving forward in our course, I'm more commonly going to be referring to it as just the concerted model. And so recall from your previous organic chemistry courses that the word concerted just means jointly happening all together at the same exact time. So concerted really just means simultaneous. And so the concerted model is just suggesting that there are simultaneous, t state to r state conversions, and all of the subunits of an allosteric enzyme. And so in other words, the concerted model is just saying that the t state to r state conversions encompasses the entire allosteric enzyme as a whole so that all of the subunits are simultaneously converting from the t state to the r state and vice versa. And so this ties directly into what's known as the symmetry rule. And so the symmetry rule just says that all of the subunits of an allosteric enzyme must always be in the same conformation or state. And so this means that all of the subunits of an allosteric enzyme must either be in the t state or all of the subunits of an allosteric enzyme must be in the r state, but there are absolutely no hybrids allowed. And so looking at our image down below over here on the left hand side, what we have is an allosteric enzyme with 4 different subunits And so notice that all 4 of these subunits of the allosteric enzyme are all in the same exact state. They're all in the t state and that is part of the symmetry rule here. And so notice that no matter how we cut this allosteric enzyme in half, if we cut it in half this way or if we cut it in half this way, we're going to have perfect symmetry. And so notice, down below here these green circles represent the allosteric enzyme with all 4 subunits in the free r state. And again, all of the subunits of an allosteric enzyme when it comes to the concerted model must always be in the same state. So they must always be in the t state or they must always be in the r state. And again, m w we know is also referred to, as the MWC model at times. And so when the allosteric enzyme converts from the t state to the r state, the conversions encompass the entire enzyme as a whole so that all 4 of its subunits are gonna convert simultaneously. And so the all of the subunits of an allosteric enzyme are always going to be in the same exact state. And so what's also important to note about the concerted model is that absolutely no substrate is needed or required to induce the fit and induce the conversion of the allosteric enzyme from the t state to the r state, which means that the allosteric enzyme is able to convert from the t state to the r state even in the absence of substrate, so even when no substrate is present. And instead, what controls the conversion of the enzyme from the t state to the r state and vice versa is just a natural equilibrium that exists between the two states, allowing for them to convert, between the two states. And so what's important to note is that even though we mentioned up above that no substrate is needed to induce this conversion. And so though no substrate is required to induce this t state to r state conversion, the changing of the substrate, essentially increasing the substrate concentration, is going to affect this t state to r state equilibrium. And so this t state to r state equilibrium is actually going to be shifted, when we increase the substrate concentration, as we'll see in our next lesson video. And so when we increase the substrate concentration, this t state to r state equilibrium is shifted towards the r state, allowing the allosteric enzyme to bind more substrate easier and therefore allowing for positive cooperativity. But again, we're going to talk more about this idea in our next lesson video. For now, down below in this portion of our image, notice it's reminding us that essentially, because all of the subunits are all And, essentially, because all of the subunits are always going to be in the same state in the concerted model, no hybrids are allowed, whatsoever. And so we can't have, within the same allosteric enzyme, one subunit in the r state, whereas the other subunits are in the t state, and we can't have any combination of, t state and r state subunits. All of the subunits must either be in the t state or all of the subunits must be in the r state. And so these are the, fundamentals to understanding the concerted MWC model. And in our next lesson video we're going to talk about how the concerted model allows for positive cooperativity and the sigmoidal kinetics of allosteric enzyme so I'll see you guys in that video
2
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Concerted (MWC) Model
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9m
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Video transcript
So in our last lesson video, we explained the basics of the concerted model. And so in this video, we're going to talk about how the model allows for positive cooperativity, and therefore explains the sigmoidal kinetics of allosteric enzymes. And so recall from our previous lesson videos, we had defined positive cooperativity. And so we have somewhat of an idea that positive cooper state, r state equilibrium in the t state, r state equilibrium in favor of the r state to essentially increase the initial reaction velocity or the v naught of the enzyme catalyzed reaction. And so it's this positive cooperativity that accounts for the sharp increase that we see with the initial reaction sigmoidal kinetics curve of allosteric enzymes. And so if we take a look at our enzyme kinetics plot down below in our image, notice that we have our sigmoidal curve right here for the allosteric enzyme. And so, we're also indicating positive cooperativity right here, and positive cooperativity is really what explains this sharp increase that we see in the initial reaction velocity, here at this stage right here. How it increases so sharply is explained by positive cooperativity. And so, again, the concerted model allows for positive cooperativity. And so, in order to understand how the concerted model allows for positive cooperativity, what we need to do is recall from our previous lesson videos that when there is no substrate concentration, essentially at very very low substrate concentrations, the equilibrium of, the t state and the r state actually favors the inactive t state. And so, if the t state is favored, of course, that means that the t state is going to be in a high concentration at these low substrate concentrations. And so, if there's a high concentration of t state, then that means that the allosteric constant l naught, is going to have a high concentration of t state and, therefore, be very large. And so, there will be a large allosteric constant l naught at low substrate concentrations. And so, under cellular conditions, even when there is low substrate concentrations, it's important to know that the allosteric enzyme can still sometimes spontaneously convert from the t state, which is going to be, again, in high abundance, to the r state, which means that even at these low substrate concentrations, even when there's no substrate present, there's still going to be some small percentage of the allosteric enzyme in the r state, even though most of the allosteric enzymes will be in the t state. And so if we take a look at our image down below to apply some of these concepts, notice, down below here we're showing you guys the concerted or the MWC model. And so notice over here we have a little key and so, these pink squares again represent the allosteric enzyme with 4 subunits all in the t state. And then, of course here what we have is the allosteric enzyme with 4 subunits all in the free R state. And of course we know that the R state is going to bind substrate more efficiently. And so, these individual, subunits are capable of binding substrates. So these yellow circles here represent the subunits with substrate bound and so this would be the allosteric enzyme with 1 subunit binding substrate. This one has 2 subunits binding substrate, 3 subunits binding substrate, and then this one down here is the allosteric enzyme with all 4 subunits binding substrate. And so notice that again at very very low, substrate concentrations, essentially when the substrate concentration is equal to 0, the equilibrium is going to favor the t state. And so that's why we have most of the allosteric enzymes here present in the t state and we have still a small percentage of the allosteric enzyme in the free r state when there's no substrate present. And so, if we go back up to our text up above, what's important to note is that as we start to increase the substrate concentrations to higher substrate concentrations, essentially increasing from the low substrate concentrations to higher substrate concentrations, it becomes more likely that the substrate molecules are going to bind to an r state subunit. And as soon as a substrate molecule binds to one r state subunit, it's going to trap all of the other subunits of the allosteric enzyme in the r state as well. And so, if we go down low, notice that, here we have 0 substrate, but as we slightly start to increase the substrate concentration, notice that, some of these subunits here, like this one right here, will bind to a substrate and once one subunit binds to a substrate, it traps the other subunits in the r state as well, making them more likely to bind substrate. And so that's exactly what we're seeing, over here. Notice that, we have one, subunit that bound substrate and this will trap the other 3 subunits here in the r state as well, making them more likely to bind substrate. And so this is exactly what we mean by positive cooperativity. The binding of 1 substrate molecule essentially leads to making it a lot easier for other substrates, so for other enzymes to bind substrate. And so, as we start to increase the substrate concentration even higher, so higher substrate concentration is going to lead to even more substrate binding, and, essentially, it's going to lead to the trapping of, allosteric enzyme subunits in the r state. And, of course, if, the, enzyme is being trapped in the r state, that's going to increase the concentration of r state. And an increase in the concentration of the r state is going to decrease the allosteric constant. And so that's why we get a lower allosteric constant. But because we have more enzymes in the r state binding substrate, that ultimately leads to an increase in the initial reaction velocity. And that is essentially what explains this sharp increase that we see here that is all related to the positive cooperativity. And so notice that, as we move to the right on, the scale here, that the substrate concentration is increasing. And as we increase the substrate concentration, we start to get more and more of the r state enzymes, and, we also start to get more and more of the r state enzymes binding to, substrates. And so we start to see more yellow as we move to the right. So you can see, we start to get a lot more yellow as we increase the substrate concentration. And, when we get more yellow, of course, that means that we have more enzyme substrate complex, and that means that we're going to have a higher reaction velocity, and that explains the sharp increase in the reaction velocity. And so, notice that at this point right here, on our curve, this is exactly where half or half here of all of the active sites are going to be occupied with substrate. And so, when the, initial reaction velocity approaches the v max, that means that all of the present enzymes are going to be bound with substrate. Essentially, all of them will look like, this with all yellow, at this point up here where it approaches v max. And so, this here, concludes our lesson on how the concerted model can explain positive cooperativity and, therefore explain the sigmoidal kinetics of allosteric enzymes. And in our next lesson video, we'll be able to talk about the other model that explains positive cooperativity as well, and that is the sequential model. So I'll see you guys in our next video.
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Problem
Problem
In the Concerted model for allosteric enzymes:
A
Relative affinities of substrate for the T & R states play a crucial role in reaction cooperativity.
B
Equilibrium between T and R states plays a minor role.
C
Enzymatic activity of the T state is considerably higher than that of the R state.
D
It is possible to describe the reactions of all allosteric enzymes accurately.
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Problem
Problem
Which of the following is true concerning the symmetry rule & the Concerted model of allosterism?
A
The protein is an oligomer of symmetrically related proteins.
B
Though not with the same affinity, the ligand can bind to a subunit in either conformation.
C
The oligomer can only exist in one of two conformational states (T & R), which are in equilibrium.
D
All the above are true.
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Problem
Problem
According to the Concerted model & symmetry rule for allosteric proteins, which of the following statements is true for hemoglobin?
A
Each of the 4 subunits in hemoglobin changes one at a time from the low affinity to high affinity state.
B
First hemoglobin's α-subunits, then β subunits change from the low to the high affinity state.
C
Each of the four subunits in the hemoglobin tetramer is either in the low affinity or the high affinity state.
D
Hemoglobin's α-subunits have a low affinity state while the β subunits have high affinity for oxygen.