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 of 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 four different types of reversible inhibitors that we already covered our competitive, uncompetitive, mixed and noncompetitive inhibitors and so notice down below. In this table, we have information on all four of these different types of reversible inhibitors organized into these rows, and so the first row has competitive inhibitors. Second row has uncompetitive inhibitors. The next to 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 V max for each of these inhibitors and then will cover the K M. 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 out compete 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 V Max is going to be unaltered, meaning that the apparent V Max is going to equal the V max. And so, for the overall effect here, off competitive inhibitors on the V Max weaken simply right in Not changed. Now again, the V max not being changed here is a unique feature of competitive inhibitors because it turns out that with all of the other reversible inhibitors, the V Max is actually always going to be decreased, and so weaken represent decreased by drawing in down arrows. And so that's pretty easy to remember, isn't it? Noticed that on Lee, the competitive inhibitor is not changed. But all of the other reversible inhibitors, the V Max, is decreased and so recall that if the substrate can compete, then it can keep the same V Max. However, if the substrate cannot compete, then it cannot keep the same. V Max and the V max will be decreased. And so now moving on to the overall effect on the K am recall that competitive inhibitors Onley bind to the free enzyme. And so Alfa is going to represent its degree of inhibition and notice that the apparent K M here eyes equal to Alfa Times, K M. And we know that Alfa must be always greater than or equal to one, which means that as we increase competitive inhibitor, the K m can Onley be increased. And so what we can do is we can write in an up arrow here, uh, to represent the cam has increased in the presence of a competitive inhibitor. Now moving on to uncompetitive inhibitor. Recall that the unique feature of uncompetitive inhibitors is this you here, Which reminds us of, Ah, you turn going downwards. Which reminds us that not only is the V Max gonna be going downwards, but so is the K. M. And so we recall that the uncompetitive inhibitors, unlike competitive inhibitors, they Onley bind to the enzyme substrate complex. Which means that Alfa Prime, uh, describes its degree of inhibition and notice that the apparent km is equal to K M over Alfa Prime. And so, Alfa Prime, uh, can Onley be greater than or equal toe one? Which means that as we increase uncompetitive inhibitor, the K M will be decreased, as we already indicated. And of course, the V Max eyes also going to be decreased as well, since, uh, it's this same V max over Alfa Prime. And so, looking down, notice that all of the apparent V max is for all of these, uh, reversible inhibitors here eyes exactly they are exactly the same, leading to the same result in the V max being decreased. And so now moving on to the mixed inhibitors. Recall that mixed inhibitors have mix some of the mixed features of competitive and uncompetitive inhibitors because mixed inhibitors combined toe either the free enzyme or the enzyme substrate complex, which means that both Alfa and Alfa prime describe its degree of inhibition. Now, uh, mixed inhibitors. Depending on if Alfa is greater than Alfa Prime or IFF, Alfa is less than Alfa Prime. They could either increase or decrease the K M. Now, if Alfa is greater than Alfa Prime, that's going to lead to an increase in the K M represented by an up arrow. And so you can see that here is well, if Alfa is greater than Alfa Prime than that means that this ratio right here will be greater than one. And anything greater than one multiplied by the cam is gonna make the cam greater. However, if the uh Alfa is less than Alfa Prime, that means that Alfa on top will be less than Alfa Prime, making this ratio smaller than one essentially a fraction and a fraction times, K m is going to make the K M smaller and so we can put in a down arrow here. And so, uh, if we move on to our next, uh, inhibitor, the noncompetitive inhibitor again recall that it's a type of 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, if Alfa is exactly equal to Alfa Prime, then this entire ratio is going to be one. And one times the K M is, of course, the K M. Which means that the K M is going to be not changed in the presence of an uncompetitive inhibitor. And so you can see here that we've been able to complete the overall effect here of all of these reversible inhibitors on the V Max and the K. M. And so, just to quantify, uh, toe qualify, what these changes mean Ah, decrease in the V. Max is actually going to be worse on DSO. You can see here that, um, the V Max eyes going to get worse and the presence of uncompetitive, mixed and noncompetitive inhibitors and then, of course, recall that the K M has an inverse relationship with binding affinity. So ah, higher K M corresponds with a, uh decreased binding affinity, which is actually going to be worse. And then, of course, a smaller K M corresponds with a stronger, binding affinity, which is actually going to be better. But recall that even though uncompetitive inhibitors appear to make the K M better, it's accompanied by a decrease in the V max, which is worse. So still uncompetitive inhibitors are going to inhibit the enzyme by making the V Max worse now, with mixed inhibitors on increase in the K M, as we already indicated, will be worse. And then a decrease in the K M, as we already indicated, will be better. But of course, the theme decreased K m here being better is accompanied by a decreased V max being worse. So again, all of these inhibitors, in one way or another, are making through the overall effect worse in one way or another. And of course not being changed, it's gonna have no effect. And so this here concludes our recap of reversible innovation and and our next lesson video will be able to do a recap of our analogies for these reversible inhibitors. So I'll see you guys there

in this video, we're going to do a recap of our school, you analogy for all of the reversible inhibitors. And so notice that here what we have is the analogy for our enzyme catalyzed reaction. Where Scooby Doo represents the free enzyme, the bone represents the free substrate and, of course, substrates bind to the active sites on enzymes. And so the active site is actually Scooby Doo's mouth. And so the bone and Scooby Doo's mouth represents the enzyme substrate complex. And then, of course, Scooby Doo eats the bone here and converts the bone into, ah, poop on the floor, which is the product. And Scooby Doo is completely unaltered and able to bind another substrate. And so, looking at our first type of reversible inhibitor, what we have is competitive inhibitors. And so when you think about competitive inhibitors, you think about competitive sports like a soccer ball here, and so the soccer ball. Because it is a competitive sport, it's going to compete with the substrate for a binding position in the Enzymes Active site, which is again Scooby Doo's mouth. And so when the competitive inhibitor is bound to Scooby Doo's mouth, it blocks the substrate from binding and therefore inhibits the enzyme. And so because the competitive inhibitor Onley binds to the free enzyme notice what we have is Alfa here the degree of innovation on the free enzyme on DSO. This is, uh, reminding us that it Onley binds to the free enzyme. And so, if we re spell competitive inhibition in this format right here, which will notice is that it's literally telling us the effect that it has on the K M. It's telling us that the K M is getting increased in the presence of a competitive inhibitor. And so here we could say that the K M is going to be increased now. Of course, when we think of competitive invasion, we think about the soccer ball, and we know that the soccer ball is going to compete with the substrate. And so if the substrate can compete, that means that it's possible for it to out compete the competitive inhibitor. And so that means that if the substrate can compete, it can keep the same the max, and so the V Max of a competitive um of the enzyme in the presence of a competitive inhibitor will not change, it will stay exactly the same. And of course as we mentioned in our previous lesson videos, If the substrate can't compete, then it can't keep the same V max, which means that it's going to be decreased. And this is going to apply for all of our other types of reversible inhibitors so we can fill in decreased for the V, Max and E and all of these scenarios. And so now moving on to our next type of reversible inhibitor. What we have is the uncompetitive inhibitor. And so I noticed that with the uncompetitive inhibitor, it's not actually going to be competing with the substrate. And so we're using Shaggy here to represent the uncompetitive inhibitor, and Shaggy is really not the most competitive looking person you can see. He's got the skinny looking arms and skinny legs. And really, if he were on a football field, he wouldn't be able to compete at all with any of the football linebackers. And so that reminds us that the uncompetitive inhibitor cannot compete with the substrate and so also recall that uncompetitive inhibitors will Onley bind to the enzyme substrate complex. And so notice that Shaggy here has a very particular mood where he's kind of upset with Scooby for pooping on his living room couch. And so he's saying here, You know what, Scoob? You've had enough bones. And so we have Alfa Prime here to remind us that Shaggy in this mood is on Lee going to bind to the enzyme substrate complex. And so that reminds us, Thea Alfa Prime reminds us of that. And of course, the you hear an uncompetitive inhibition reminds us of the u turn. And of course, uh, even though it seems that the K M is going to be increased, we have to remember that the U turn actually means that the K M is going to be decreased along with the V Max also being decreased. So the U turn here pointing downwards reminds us that both the K M and the V Max are going to be decreased. So now moving on to our next type of reversible inhibition. What we have is mixed inhibition and notice. Again, we're using Shaggy to represent our mixed inhibitor. And again, Shaggy is not the most competitive looking person. And so shaggy eyes not going to compete with the substrate and mixed inhibitors do not compete with the substrate. And so notice here that Shaggy actually has mixed emotions. Notice that it has the same emotion as the uncompetitive inhibitor on DSO. It will actually bind to the enzyme substrate complex with Alfa Prime here. But also Shaggy has an opposite mixed emotion where he loves Scooby Doo. We do so much that he will actually bind to Scooby Doo even when he doesn't have the substrate or the bone in his mouth. And so that's why we have Alfa Prime here, similar to how we had Alfa prime up here with the competitive inhibitor, uh, reminding us that the mix inhibitor combined to either the free enzyme or it combined to the enzyme substrate complex to inhibit the reaction. And so recall that with mixed inhibition, because we know it always decreases the V Max. Um, we also know that with mixed inhibition, that it could potentially either increase or decrease the K M depending on the value of Alfa and Alfa Prime, And so recall that if we write mixed in this fashion, the X and mixed constrained for a greater than and a less than sign. And so when Alfa is greater than Alfa Prime, uh, pointing in this direction right here, you can see that it's emphasizing the I, which reminds us that it will be increased so the K M will be increased when Alfa is greater than Alfa Prime has indicated here. However, when Alfa is less than Alfa Prime Aziz indicated by this side of the ex, uh, that's going to lead to a decrease in the K M. And so you could see that the K M will be decreased when Alfa is less than Alfa Prime. And so now moving on to our final type of reversible inhibitor. What we have is the non competitive inhibitor. And so, with the noncompetitive inhibitor recall that really, it's a type of mixed inhibitor. And so what that means is that Alfa and Alfa Prime are both going to be in the play. And we're using the same exact, um, Shaggy here with mixed emotions, as we use with mixed inhibitors. And that reminds us that again, uh, noncompetitive inhibitors do not compete with the substrate and noncompetitive inhibitors combined to either the free enzyme or to the enzyme substrate complex and so notice that the unique feature of noncompetitive inhibitors is that it starts here with no and no reminds us that there is no change to the K M. And so we can say that there's no K m change. And this is because noncompetitive inhibitors are 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. And so, of course, because there's no competition here, the V Max is going to be decreased. And so hopefully using this analogy here can help you guys better memorized the effects that thes reversible inhibitors have on enzymes. And so the MAWR practice. You get utilizing these analogies and, uh, these memory tools, the better off you'll be. So I'll see you guys in our practice videos where we'll be able to get some practice applying all of these concepts all over again. So see you guys there

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.