Noncompetitive Inhibition

in this video, we're going to talk about our fourth type of reversible inhibition, which is noncompetitive inhibition. And so, of course, noncompetitive inhibition is going to be caused by non competitive enzyme inhibitors. And so, as you may have already assumed, non competitive enzyme inhibitors do not compete with the substrate for binding. And that's because noncompetitive enzyme inhibitors, as we've mentioned before in some of our previous lesson videos, are really just a specific type of mixed inhibitor. And mix. Inhibitors don't even mention competition whatsoever, so of course they're not going to compete. And so, because again, noncompetitive enzyme inhibitors are just a specific type of mixed inhibitor. Noncompetitive enzyme inhibitors also have mixed binding to the enzyme and bind to Alice Derek sites on either the free enzyme or the enzyme substrate complex. And as we know from our previous lesson videos, all enzyme inhibitors, regardless of what type they are, are going to lower or decrease the initial reaction velocity or the V, not of an enzyme catalyzed reaction. So again, no surprise here. And so, of course, ultimately, the binding of a noncompetitive inhibitor to either the free enzyme or the enzyme substrate complex is going to prevent the conversion of the substrate into the product. And again, we already knew this from our previous lesson videos. Because any time the inhibitor is bound to the enzyme, uh, it's going to inhibit the reaction and prevent the enzyme from catalyzing the reaction. Now one of the defining features of non competitive enzyme inhibitors is that they actually bind with the same exact binding affinity to the free enzyme and to the enzyme substrate complex, which is something different than, uh, other typical mixed inhibitors do. And so what this means is that non competitive enzyme inhibitors, um, the inhibition constant of the free enzyme K I is going to be exactly equal to the inhibition constant of the enzyme substrate complex K Prime I, which is again This is something different. That was not true with other types of mixed inhibitors in our previous lesson videos. And so if we take a look at our example down below of noncompetitive inhibition, this image should look pretty familiar to you guys because it's actually the same exact image that we used for mixed enzyme inhibitors. And so again, that's because again noncompetitive inhibitors are just a type of mixed inhibitor. And so, over here on the left hand side, we have the same exact enzyme catalyzed reaction and noticed that the non competitive enzyme inhibitor can bind to the free enzyme or to the enzyme substrate complex. And really, the main difference between, um mixed inhibitors and noncompetitive inhibitors is that mixed inhibitors bind with the same exact affinity to the free ends I'm and to the enzyme substrate complex. And so again, what this means is that the mix inhibitor will bind to the free. Uh, on the mix inhibitor will bind to the E s with the same exact affinity. And again, we'll talk more about the effects of noncompetitive inhibitors. Um, in our next lesson video, and we'll also relate it back to our pneumonic. So I'll see you guys in our next video

in this video, we're going to talk about the effects that noncompetitive inhibitors have on enzymes, and so noncompetitive enzyme inhibitors will actually not have an effect on the apparent K M. But they do decrease the apparent the max. And so the question is exactly how and why is it that noncompetitive enzyme inhibitors have this effect here on enzymes? And to understand that, let's take a look down below at our analogy in this image and notice that this image right here is practically exactly the same as the image that we used in mixed inhibition. And that's again because noncompetitive enzyme inhibitors really are mixed inhibitors, their type of mixed inhibitor. And so again, we're using Shaggy here to represent the non competitive enzyme inhibitor. And, of course, Shaggy is not very competitive. It also the noncompetitive inhibitor, will not compete with the substrate. And so again, because we cover this analogy before in our previous lesson, videos of mixed inhibitors. I'll save you some time. We won't go through it again. And so let's go back on up to our text and revisit exactly how and why non competitive enzyme inhibitors have these effects here and so will first visit the effect of not having any effect on the apparent K M. And of course, the K M is going to be determined by list shot liaise principle of this particular equilibrium. And so, as we've mentioned briefly before in our previous lesson videos, when the degree of inhibition on the free enzyme Alfa is exactly equal to the degree of inhibition on the enzyme substrate complex Alfa prime, then what? Essentially what that means is that the free enzyme here and the enzyme substrate complex here are going to be inhibited exactly the same. Which means that the concentration of free enzyme is going to be decreased exactly the same as the concentration of enzyme substrate complex. And so what this means is that the shift to the left is going to be canceled out by the shift to the right. And so because these two reactions shifts cancel each other out completely, there is actually no overall reaction shift when it comes to these noncompetitive inhibitors. And so this no, here in the noncompetitive inhibitor is quite unique when we compare the different types of reversible inhibitors that we've covered and so the no and the noncompetitive inhibitor can remind you that there is no change to the apparent K M because there is no overall reaction shift now. Now that we understand why it is that noncompetitive inhibitors do not affect the K M. Let's move on to how they decrease the apparent V Max. And of course, this is gonna have to do with the fact that there is no competition, so noncompetitive inhibitors do not compete with the substrate. And so that's why we have Shaggy here, one of our most non competitive people that we know and it does not compete. He does not compete with the substrate, and so this means that the substrate does not have an opportunity to out compete the noncompetitive inhibitor. And so, since the substrate cannot out compete, the noncompetitive inhibitor. This means that the effects of the noncompetitive inhibitors are not going to be reversed even when we increase the substrate concentrations to saturating levels. And of course, we know that all enzyme inhibitors, regardless of what type, are going to decrease the initial reaction velocity, and so that decrease initial reaction velocity will translate to a decreased apparent V max. If the effects cannot be reversed. And so, uh, now that we know that noncompetitive inhibitors decrease the apparent V max, we also know that that translates to the catalytic constant or the K cat or the turnover number also being decreased as well, the same as we saw with mixed inhibitors and uncompetitive inhibitors and so down below. And our image noticed that the decreased K cat is, ah result of the decreased V max. And of course, the total enzyme concentration is not being affected here. And so you might be wondering, How could you possibly memorize all of these different effects of noncompetitive inhibitors? And that's exactly why we have this box down here. And so again, when it comes to noncompetitive inhibitors, you really want to focus on this big? No here, because that reminds us that there's absolutely no change to the K M. And so you can see noncompetitive. There's no change to the K M. And again, this has to do with the fact that the degree of inhibition on the free enzyme Alfa is exactly equal to the degree of inhibition on the enzyme substrate complex, Alfa Prime and again, since there's no competition with non competitive enzyme inhibitors. That means that the non competitive enzyme inhibitor does not compete with the substrate. And so if the substrate is not able to compete, if the substrate can't compete, it can't keep the same V max. And, of course, if it can't keep the same V Max, that V Max is going to be decreased in the presence of an inhibitor. And so this here concludes our lesson on the noncompetitive inhibitor effects. And in our next lesson video, we'll talk about how noncompetitive inhibitors affect the McHale is meant in plots, so I'll see you guys there.

so now that we know that non competitive enzyme inhibitors do not affect the apparent K M. But they do decrease the apparent V Max in this video, we're going to talk about how noncompetitive inhibitors affect the makayla is meant in plot and so recall from our previous lesson videos that non competitive enzyme inhibitors are really just a specific type of mixed inhibitor, which means that non competitive enzyme inhibitors will have mixed binding to the enzyme and combined either to the free enzyme or to the enzyme substrate complex, which means that the degree of inhibition on the free enzyme and the degree of inhibition on the enzyme substrate complex, Alfa and Alfa Prime will measure its degree of inhibition. And so when it comes down to it, a noncompetitive inhibitor is a mixed inhibitor where the degree of inhibition on the free enzyme Alfa is exactly equal to the degree of inhibition on the enzyme substrate complex, Alfa Prime. And so since Alfa is equal to Alfa Prime with a noncompetitive inhibitor, as we already know from our previous lesson video, this leads to no change to the apparent K M. And so that means that the apparent km is going to be exactly equal to the K M and, of course, the degree of inhibition on the enzyme substrate complex. Alfa Prime is always going to lead to a decreased the max, a decreased apparent V max. And so here you can see that the parent V Max is defined as the V Max over Alfa Prime. And so if we take a look down below it, our image in our example notice over here on the left hand side, we're showing you the Mikhail's meant an equation in the presence of a noncompetitive inhibitor and notice that this Mikhail's meant an equation is exactly the same as the McHale is meant. An equation in the presence of a mixed inhibitor, which goes to show that really a noncompetitive inhibitor is a type of mixed inhibitor where the degree of inhibition on the friends I'm Alfa is exactly equal to the degree of inhibition on the enzyme substrate complex, Alfa Prime. And so, if Alfa is exactly equal to Alfa Prime, what that means is that this ratio right here is going to cancel out and we're just going toe have the K M, which shows that the K M is not being changed and really, it's just the V Max here that's going to be decreased. And so if we take a look over here at this, Mikhail is meant in plot notice again that all enzyme inhibitors, regardless of what type, are going to decrease the initial reaction rate or the initial reaction velocity the not. And so notice that with these two curves, this black curve here is the enzyme catalyzed reaction and the absence of inhibitor. And this blue curve right here is the enzyme catalyzed reaction in the presence of noncompetitive inhibitor and, of course, noticed that there is this decrease in the V max. And so the v max of, um, the enzyme catalyzed reaction in the presence of noncompetitive inhibitor is being decreased. However, notice that with a non competitive enzyme inhibitor, there is not a change to the K M. So the K M is exactly equal to the apparent K M. And so we can see that here in this McHale is meant and plot. And so this here concludes, Our lesson on how noncompetitive inhibitors affect the McHale is meant and plot, and in our next lesson. Video. We'll talk about how noncompetitive inhibitors affect the line. Weaver Burke plot. So I'll see you guys in that video.

in this video, we're going to talk about how noncompetitive inhibitors affect the line. Weaver Burke plot And so again, recall that way. Back in some of our previous lesson videos, we talked about shifting line Weaver Burke plots and, ah, lot of the skills that we developed in those older videos are going to be very useful here in this lesson. And so if you don't remember much about shifting line Weaver Burke plots, make sure to go back and check out those older videos before you continue here. Now, that being said, it turns out that the slope of the line on a line weaver bird plot, which is, of course, the ratio of the K M over the V max is actually going to increase so it increases with Mawr noncompetitive inhibitor. And so the reason for this is because recall from our previous lesson videos that noncompetitive enzyme inhibitors always decrease the apparent V max, but they have no effect on the apparent K M. And so if the K M is unchanged, but the V Max is actually being decreased, a smaller number in the bottom half of this denominator is actually going to increase the slope, as we've already mentioned, and so also recall that ah, line Weaver Burke plot is known as a double reciprocal plot. And so even though the apparent V max decreases the Y intercept, which is the reciprocal of the V, Max is going to increase in the presence of a noncompetitive inhibitor. But of course, since there's no effect on the apparent K M in the presence of a noncompetitive inhibitor, the X intercept, which is the negative reciprocal of the K M, is also not going to be affected. So it's going to stay exactly the same. And so if we take a look down below at our image notice on the left hand side we have the line. We have Robert Equation in the presence of a noncompetitive inhibitor, and so really, all we need to do is take. The McHale is meant in equation in the presence of a noncompetitive inhibitor, which we covered in our last lesson video and take the reciprocal of that. And that's what will give us this equation here. And so over here on the right. What we have is a line Weaver Burke plot and the Black Line here represents the enzyme catalyzed reaction in the absence of inhibitor, whereas this purple line here represents the enzyme catalyzed reaction in the presence of noncompetitive inhibitor. And so notice that even in the presence of the noncompetitive inhibitor that the K M is not being affected. And we can tell because the X intercept is not changing, however, noticed that the Y intercept of the line in the presence of inhibitor is actually being increased as we mentioned up above the why intercept is increasing. However, an increased why intercept is getting further away from this zero marker which we know access the infinity marker for the V Max. And so because it's getting further away from the infinity marker, the V Max is actually being decreased as we mentioned up above. And so if we were to add even mawr noncompetitive inhibitor, if we would go ahead and add plus two concentration of inhibitor, of course, the K M is still not going to change, So we're gonna have the same exact X intercept. But the V Max is going to decrease even further, and so we're gonna have a line that looks something along the lines of this and so notice that in the presence of Mawr noncompetitive inhibitor, the slope actually increases further. And so this here concludes our lesson on how noncompetitive inhibitors affect line Weaver Burke plots, and our next video will be able to get some practice utilizing all these concepts, so I'll see you guys there.