Recap of Reversible Inhibition - Online Tutor, Practice Problems & Exam Prep

Reversible enzyme inhibitors can be categorized into four types: competitive, uncompetitive, mixed, and noncompetitive. Competitive inhibitors increase the Michaelis constant (K_m) but do not change V_max. Uncompetitive inhibitors decrease both K_m and V_max. Mixed inhibitors can either increase or decrease K_m depending on their binding affinity, but always decrease V_max. Noncompetitive inhibitors, a subtype of mixed inhibitors, do not alter K_m but decrease V_max. Understanding these effects is crucial for grasping enzyme kinetics.

Recap of Reversible Inhibition

In this video, we're going to do a recap of reversible inhibition, and so because this is a recap of all the common types of reversible inhibitors that we already covered in our previous lesson videos, really, there's no new information in this video, which means that if you already feel like an expert on these reversible inhibitors, then feel free to skip this entire video since really there's no new information. But if you're struggling with these reversible inhibitors even just a little bit, then this video could potentially be very valuable for you.

And so recall that the 4 different types of reversible inhibitors that we already covered are competitive, uncompetitive, mixed, and noncompetitive inhibitors. And so notice down below in this table, we have information on all 4 of these different types of reversible inhibitors organized into these rows. And so the first row has competitive inhibitors, the second row has uncompetitive inhibitors, the next two rows are for mixed inhibitors, and then the last row is for noncompetitive inhibitors. And notice that the mixed and the noncompetitive inhibitors have the same exact pink background. And that's because recall that noncompetitive inhibitors are really just a type of mixed inhibitor. And so, notice that there's a lot of information here in this table, but really all I want you guys to focus the most on is this last column here, the overall effect that the inhibitors have on the enzyme.

And so, first, we're gonna focus on filling out the overall effect on the Vmax for each of these inhibitors, and then we'll cover the KM. And so, looking at this first row here for competitive inhibitors, recall that the unique feature of competitive inhibitors is that they can actually compete with the substrate whereas all of these other reversible inhibitors cannot compete with the substrate. And so because competitive inhibitors can compete with the substrate, this means that it's possible for the substrate to outcompete the competitive inhibitor and completely negate its effects. Meaning, it can make the effects of the competitive inhibitor negligible when we increase the concentration of substrate a lot. And so that means that the Vmax is going to be unaltered, meaning that the apparent Vmax is going to equal the Vmax. And so, for the overall effect here of competitive inhibitors on the Vmax, we can simply write in not changed. Now, again, the Vmax not being changed here is a unique feature of competitive inhibitors because it turns out that with all of the other reversible inhibitors, the Vmax is actually always going to be decreased, and so we can represent decreased by drawing in down arrows. And so, that's pretty easy to remember, isn't it? Notice that only the competitive inhibitor is not changed, but all of the other reversible inhibitors, the Vmax is decreased. And so recall that if the substrate can compete, then it can keep the same Vmax. However, if the substrate cannot compete, then it cannot keep the same Vmax and the Vmax will be decreased.

And so, now moving on to the overall effect on the KM, recall that competitive inhibitors only bind to the free enzyme. And so alpha is going to represent its degree of inhibition. And notice that the apparent KM here, is equal to alpha times KM and we know that alpha must be always greater than or equal to one, which means that as we increase competitive inhibitor, the KM can only be increased. And so, what we can do is we can write in an up arrow here, to represent that the KM is increased in the presence of a competitive inhibitor. Now, moving on to uncompetitive inhibitor, recall that the unique feature of uncompetitive inhibitors is this u here, which reminds us of a u-turn going downwards, which reminds us that not only is the Vmax gonna be going downwards, but so is the KM. And so, we recall that the uncompetitive inhibitors, unlike competitive inhibitors, they only bind to the enzyme substrate complex, which means that alpha prime, describes its degree of inhibition. And notice that the apparent KM is, equal to KM over alpha prime. And so alpha prime, can only be greater than or equal to 1, which means that as we increase uncompetitive inhibitor, the KM will be decreased as we already indicated. And, of course, the Vmax, is also going to be decreased as well since, it's the same, Vmax over alpha prime. And so, looking down, notice that all of the apparent Vmaxes for all of these reversible inhibitors here, are exactly the same, leading to the same result in the Vmax being decreased.

And so, now moving on to the mixed inhibitors, recall that mixed inhibitors have mixed some of the features of competitive and uncompetitive inhibitors because mixed inhibitors can bind to either the free enzyme or the enzyme substrate complex, which means that both alpha and alpha prime describe its degree of inhibition. Now, mixed inhibitors, depending on if alpha is greater than alpha prime or if alpha is less than alpha prime, they could either increase or decrease the KM. Now if alpha is greater than alpha prime, that's going to lead to an increase in the KM represented by an up arrow. And so, you can see that here as well. If alpha is greater than alpha prime, then that means that this ratio right here will be greater than 1 and anything greater than 1 multiplied by the KM is going to make the KM greater. However, if the alpha is less than alpha prime, that means that alpha, on top will be less than alpha prime making this ratio smaller than 1, essentially a fraction and a fraction times KM is going to make the KM smaller. And so, we can put in a down arrow here. And so, if we move on to our next inhibitor, the noncompetitive inhibitor, again, recall that it's a type of mixed inhibitor where, the degree of inhibition on the free enzyme alpha is exactly equal to the degree of inhibition on the enzyme substrate complex alpha prime. And so if alpha is exactly equal to alpha prime, then this entire ratio is going to be 1 and one times the KM is,

Recap of Reversible Inhibition

In this video, we're going to do a recap of all of the different analogies and memory tools that we've created to help you memorize the effects of the reversible enzyme inhibitors. And so notice here what we have is an image to represent our analogy for the enzyme-catalyzed reaction. Where we have this adorable cute little puppy named Zyme to represent our free enzyme, and then we've got this bone to represent our substrate. And then of course we know that the substrate will bind to the enzyme specifically at the enzyme's active site, which is represented by the dog's mouth. And so when this substrate bone binds to the enzyme's active site, or the dog's mouth, as it is over here in this image, it forms the enzyme-substrate complex. And then, of course, the dog can eat the bone and catalyze this reaction unaltered while creating a poop on the ground. And the poop here represents the product. And so let's take a look at our very first reversible inhibitor, which is going to be the competitive enzyme inhibitor. And so recall that when we think of competitive enzyme inhibition, we can think of competitive sports such as soccer and this soccer ball that you see right here. And the soccer ball is going to represent our competitive enzyme inhibitor.

Now it's very important to note here that competitive enzyme inhibitors are the only enzyme inhibitor to display this competition feature with the substrate. And so the competitive enzyme inhibitors, the only reversible inhibitor that we're going to discuss, that will actually compete with the substrate for a binding position to the enzymes active site, which is again the dog's mouth. And so the competitive enzyme inhibitor soccer ball will only bind to the free enzyme at the active site and compete with the substrate for a binding position to that active site. And so this is exactly why we have the Greek symbol alpha here. Recall that the Greek symbol alpha here is symbolizing the degree of inhibition on the free enzyme. And And so this reminds us that competitive enzyme inhibitors will only bind and inhibit the free enzyme.

Now if we rewrite competitive inhibition in this manner that you see right here, then you can see that it's pretty much telling us the effect that it has on the Michaelis constant or the Kilometers. It's telling us that the Kilometers is going to be increased. And so over here, we can indicate that the Michaelis constant or the Kilometers is increased in the presence of a competitive enzyme inhibitor. And again, the competitive enzyme inhibitor is the only inhibitor to display this unique competition feature with the substrate and compete with that substrate for a binding position to the enzyme's active site. And so if the substrate and the inhibitor compete with each other, that means it is possible for the substrate to outcompete the inhibitor. And we can do that by increasing the concentration of substrate a lot. In other words, adding a huge pile of bones here so that the substrate concentration is near saturating levels. And so if the substrate can compete, that means that it can also outcompete the inhibitor, and that means that it can keep the same exact v max. And so the v max will be unaltered or unchanged in the presence of a competitive enzyme inhibitor.

Now again, that competition feature is unique to competitive inhibition. So for all of the other reversible inhibitors that we're gonna talk about down below, notice that the substrate cannot compete. And if the substrate can't compete, then, of course, it can't keep the same v max, and that means that the v max will be decreased. And so that means that for all of these other reversible inhibitors, the v max is going to be decreased. And so we can go ahead and fill in that blank with decreased for all of these other reversible inhibitors. And so this is also the reason why we use the owner of our puppy to represent these reversible inhibitors. Because recall that the owner of our puppy is one of the most uncompetitive people or, one of the people that is not competitive at all. And he's wearing a shirt that says we are all winners. And so he has no interest in competing with anyone or anything, including the substrate bone. And that means that the substrate cannot outcompete, and that means that the v max is going to be decreased for all of these, reversible inhibitors.

And so let's move on to our second type of reversible inhibitor, which is going to be the uncompetitive, enzyme inhibitor. And, of course, we're using the owner of our puppy to represent the uncompetitive enzyme inhibitor. But notice that the owner of our puppy is in a pretty bad mood. He's very upset. You can tell by his facial features, and he's upset because the puppy keeps on pooping on his couch or on his living room floor. And so he's upset with the puppy when the puppy has the bone in its mouth. So he is going to be associated with the enzyme substrate complex form of our puppy with the dog, which is the dog with the bone in its mouth. And so that's exactly why we have this symbol here, alpha prime. And alpha prime is the degree of inhibition on the enzyme substrate complex. And so this reminds us that our uncompetitive enzyme inhibitor will only bind to the enzyme substrate complex. And so notice here he's upset with the puppy and he's saying drop the bone, Zyme. And again, Zyme is the name of our puppy that represents the enzyme.

Another unique memory tool that we can focus on here is the u, which is quite unique. It's a unique letter amongst this, these reversible inhibitors. And so this u can remind you of a u-turn. And so when we rewrite uncompetitive inhibition like this, although it may seem that it's saying the kilometers is increased, when we consider the u-turn, the u-turn pretty much tells us that the kilometers is going to be decreased. And so the kilometers is going to be decreased along with the v max being decreased, and they will be proportionally decreased, meaning that they will be decreased by the same percentage.

And so we can move on to our 3rd type of reversible inhibitor, which is going to be the mixed enzyme inhibitor. And so when you think of mixed enzyme inhibitors, you can think of our owner with mixed emotions. And so notice that we have not only the angry upset version of our owner, but we also have the happy, loving version of our owner. So he has mixed emotions. And notice that the loving version of our owner is going to love the free enzyme version of our puppy. And so that's why we have alpha here, the degree of inhibition on the free enzyme. And then the upset version of our owner, who's upset with the enzyme substrate complex form, has the alpha prime symbol to remind us that it's associated with, the enzyme substrate complex. And so mixed enzyme inhibitors can bind to both the free enzyme and the enzyme substrate complex.

The question is, does the mix inhibitor have a greater effect on the free enzyme or does it have a greater effect on the enzyme substrate complex? And what we'll determine that are the values of alpha and the values of alpha prime. And so when alpha is greater than alpha prime, then we can say that the Michaelis constant, or the Kilometers, will be increased. However, when alpha is less than alpha prime, then we can say that the Kilometers will be decreased. And so what can help us remember this is if we rewrite mixed in this fashion that you see right here, where the x in mixed can be used to represent a greater than symbol and a less than symbol. And so, again, if alpha is greater than alpha prime, then that's leading to this I here, and the I can remind you of the I in increased. And if alpha is less than alpha prime then that's leading to this d here, and the d can remind you of decreased. And so depending on the value of alpha and alpha prime, and if alpha is greater than alpha prime or alpha is less than alpha prime, that will dictate whether or not a Kilometers will be increased or decreased. And so there are some mixed enzyme inhibitors that will increase the Michaelis constant, and there are other mixed enzyme inhibitors that will decrease the Michaelis constant. However, all mixed enzyme inhibitors are going to decrease the v max, and then that is again because the substrate can't compete. And if the substrate can't compete, then it can't keep the same vmax. And so notice here we have these symbols here in between, the greater than and the less than symbols here, to help remind you that mix enzyme inhibitors will either bind, more greatly to the free enzyme or more greatly to the enzyme substrate complex.

And then last but not least, the 4th type of reversible inhibitor that we have is the non competitive enzyme inhibitor. And really this is just a specific type of mixed inhibitor. And so what you'll notice is that the image here is exactly the same as the image here, except for the fact that alpha is going to be exactly equal to alpha prime. And that's why we have the equal to symbol here, right in between them. And so what we're saying is that our owner is going to have equally, mixed emotions towards the free enzyme and the enzyme substrate complex. And so the noncompetitive, inhibitor here, if we use the no as a memory tool, it's telling us that there is no change in the Kilometers. And so that means that when alpha is equal to alpha prime, there will be no Kilometers change. And so again, we're using the owner here, which is not a very competitive person. And since there's no competition, if the substrate can't compete, it can't keep the same v max, and so the v max will be decreased.

And so this here concludes our recap on these analogies and memory tools. And hopefully by, continuing to practice these analogies and memory tools, you'll be able to get the hang of this very quickly and you'll be able to ace your next exam. And so I'll see you all in our next videos, we'll we'll be able to apply many of these concepts.

Below are kinetic data comparing aldehyde dehydrogenase activity in the absence and presence of Agent A. What type of inhibitor is Agent A?

• A. Competitive inhibitor.
• B. Noncompetitive inhibitor.
• C. Uncompetitive inhibitor.
• D. Irreversible inhibitor.

Which of the following statements are true about enzyme inhibitors?

• A. Competitive inhibitors change the slope of the Lineweaver-Burk line but not the y-intercept.
• B. Noncompetitive inhibitors are a type of mixed inhibitor.
• C. Uncompetitive inhibitors change Km & Vmax in a way to create a parallel Lineweaver-Burk line.
• D. Noncompetitive inhibitors result in lines with increasing [I] to share the same x-intercept.
• E. All the above are true.

Complete the chart below.

Alright. So this practice problem just wants us to complete the chart down below, which is really just a chart of the reversible inhibitors that we covered in our previous lesson videos. And so this first row here wants us to determine the binding site for each of these reversible inhibitors. And so recall from our previous lesson videos that competitive enzyme inhibitors will compete with the substrate for a position in the enzyme's active site, so competitive inhibitors bind to the enzyme's active site, whereas all of these other reversible inhibitors will bind to some other allosteric site. And so, essentially, we can do is just take this and repeat this a few times here because it is the allosteric site. And so now, we can move on to the next row, which is the Kilometers change. Now for competitive inhibitors, we know that the Kilometers is going to be increased. And so what we can say is that the Kilometers is going to be increased with competitive inhibitors. Now for uncompetitive inhibitors, we focus on this u, and the u reminds us of a u-turn, which means that everything's going to be going down, which means that both the kilometers are going to be decreased and so is the vmax also going to be decreased. Now, moving on to mixed inhibitors, the Kilometers of mixed inhibitors can actually either increase or decrease. And so what we're going to write here is that it depends on the values of alpha and alpha prime. So, recall that if alpha is greater than alpha prime, that's going to lead to an increase in the Kilometers. Then, of course, if the opposite is true, alpha is less than alpha prime, that's going to lead to a decrease. So now moving on to non-competitive inhibitors. Non-competitive inhibitors have this no in them, and so that reminds us that there's no change to the km. So we'll say no change. So now moving on to the vmax change of competitive inhibitors, recall that if the substrate can compete, then this, the enzyme can keep the same vmax. So, with competitive inhibitors, because there is competition between the substrate and the competitive inhibitor, that means that the vmax can be kept the same. And so, essentially what we'll say is that there is no change to the Vmax, with competitive inhibitors. We already determined that the vmax of uncompetitive, in the presence of uncompetitive inhibitors is decreased. And so with mixed, and non competitive inhibitors, all of the vmax change will be decreased. And so we can indicate a decreased vmax for all of these. And so now that we filled out these first three rows here, what we can do is utilize those three rows to determine the change in the Michaelis Menten plot, as well as the change in the Lineweaver Burk plot. And so starting off with competitive inhibitors, we know that ultimately what's going to happen is, the vmax is not going to be changed, which means that it's going to reach the same point up here by the end and, the kilometers are going to be increased. And so essentially, it's going to look something along the lines of this, where the kilometers are now somewhere over here. So we can clearly see that there has been an increase in the kilometers and, notice that the vmax is not changed. And so, if we apply this to the Lineweaver Burk plot down below, if the black line here represents the uninhibited line, again, we know that the competitive inhibitor leads to an increase in the Kilometers. And so, recall that the 0, marker on a Lineweaver Burk plot acts as the infinity marker. And so if we want to increase the km, we need to move the x-intercept closer to the 0 infinity marker. And so essentially what we're saying is that it's going to have a larger kilometers. But, again, there's no change to the vmax, which means that it's going to cross the y-axis and have the same y-intercept. And so this line right here would represent the competitive inhibitor. So now moving on to uncompetitive inhibitor here. Ultimately what we'll see is that there is a decrease to the Kilometers and a decrease to the vmax. And so ultimately, it's going to look something along the lines of this, where you can see that the km here is going to be somewhere about right here. So we're going to have a decreased kilometers, and again, the vmax is also being decreased. And so, if we apply that to our Lineweaver Burk plot down below, again, the black line here represents the uninhibited line, and so a decreased kilometers means that it's going to get further away from the 0 infinity marker, and so the x-intercept is going to move further away. So we'll have a point right over here. And, of course, the vmax is also going to decrease, which means it's going to get further away from the 0 infinity marker as well. And, it's going to be decreased proportionally, and really that is the key of uncompetitive inhibitors. So, again, we remind ourselves of a u-turn, so you think, okay, well, this is just going to make a u-turn like this and it's going to create a parallel line. And so these two lines here are going to be parallel to each other. Now moving on to mixed inhibition here, of course, we know that there's going to be a decrease to the vmax and whether or not the kilometers increases or decreases depends on the values of these alpha and alpha prime. And so if alpha is greater than alpha prime here in green, we know that there's going to be an increase to the km. And an increase to the km means that the x-intercept will be moved closer towards the 0 infinity marker, so it'll be a point over here. And, of course, the vmax is going to be decreased, which means it'll get further away from the 0 infinity marker. So it'll look like this. And then if we apply it when alpha is less than alpha prime, that's going to lead to a decrease in the Kilometers. So a decreased Kilometers is going to get further away from the 0 infinity marker.

Here’s what students ask on this topic:

What are the different types of reversible enzyme inhibitors?

Reversible enzyme inhibitors can be categorized into four main types: competitive, uncompetitive, mixed, and noncompetitive inhibitors. Competitive inhibitors bind to the free enzyme and compete with the substrate for the active site, increasing the Michaelis constant (K_m) but not changing V_max. Uncompetitive inhibitors bind only to the enzyme-substrate complex, decreasing both K_m and V_max. Mixed inhibitors can bind to either the free enzyme or the enzyme-substrate complex, and they always decrease V_max but can either increase or decrease K_m depending on their binding affinity. Noncompetitive inhibitors, a subtype of mixed inhibitors, do not alter K_m but decrease V_max.

How do competitive inhibitors affect enzyme kinetics?

Competitive inhibitors affect enzyme kinetics by binding to the free enzyme and competing with the substrate for the active site. This competition increases the Michaelis constant (K_m), indicating a decreased binding affinity between the enzyme and the substrate. However, because the substrate can outcompete the inhibitor at high concentrations, the maximum reaction velocity (V_max) remains unchanged. The equation for the apparent K_m in the presence of a competitive inhibitor is K_m,app = αK_m, where α is the degree of inhibition and is always greater than or equal to 1.

What is the effect of uncompetitive inhibitors on K_m and V_max?

Uncompetitive inhibitors bind only to the enzyme-substrate complex, leading to a decrease in both the Michaelis constant (K_m) and the maximum reaction velocity (V_max). This type of inhibition results in a proportional decrease in K_m and V_max, meaning they are reduced by the same percentage. The equations for the apparent K_m and V_max in the presence of an uncompetitive inhibitor are K_m,app = K_m/α' and V_max,app = V_max/α', where α' is the degree of inhibition and is always greater than or equal to 1.

How do mixed inhibitors differ from noncompetitive inhibitors?

Mixed inhibitors can bind to either the free enzyme or the enzyme-substrate complex, affecting both the Michaelis constant (K_m) and the maximum reaction velocity (V_max). Depending on their binding affinity, mixed inhibitors can either increase or decrease K_m, but they always decrease V_max. Noncompetitive inhibitors are a specific type of mixed inhibitor where the degree of inhibition on the free enzyme (α) is equal to the degree of inhibition on the enzyme-substrate complex (α'). This equality results in no change in K_m, but V_max is still decreased.

Why does V_max remain unchanged in the presence of competitive inhibitors?

V_max remains unchanged in the presence of competitive inhibitors because these inhibitors compete with the substrate for binding to the enzyme's active site. At high substrate concentrations, the substrate can outcompete the inhibitor, allowing the enzyme to reach its maximum reaction velocity (V_max). Therefore, while the apparent Michaelis constant (K_m) increases, indicating a decreased binding affinity, the V_max remains the same as it would be without the inhibitor.