7. Enzyme Inhibition and Regulation
Irreversible Inhibition
1
concept
Irreversible Inhibition
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So now that we've introduced enzyme inhibition in this video, we're going to talk about our first category of enzyme inhibition, which is irreversible inhibition. Now, of course, irreversible inhibition is caused by irreversible inhibitors, and irreversible inhibitors are just enzyme inhibitors that bind very, very, very tightly and pretty much irreversibly to the enzyme to not only decrease its activity but completely stop or halt the enzymes activity pretty much decreasing the enzymes. Initial reaction velocity or V not all the way down to zero. Now these irreversible inhibitors conform stable co Vaillant bonds with the enzyme. And because these are such stable Covalin bonds, they are very, very difficult to break, which is why thes bonds are pretty much irreversible and because irreversible inhibitors pretty much stop and and activate. The enzyme activity there, also known as in activators and so in activators and irreversible inhibitors are pretty much synonyms with each other. Now it's important to note that one irreversible inhibitor will permanently neutralize or remove one active enzyme, so it's a one toe one ratio. And if we want to inactivate all of the enzyme that's present, then we need to add the same exact amount of irreversible inhibitor. Now these irreversible inhibitors, or activators, are often powerful poisons. However, they can also be used by doctors as drugs and medicine as well. Now notice down below. In our example image, we're showing you how an irreversible inhibitor can interact with a free enzyme and form the enzyme inhibitor complex. However, irreversible inhibitors can also interact with the enzyme substrate complex as well to form the enzyme substrate and OC inhibitor complex. Here we're just showing you one version, but it can actually bind Thio both the free enzyme as well as the enzyme substrate complex. But really the main point of irreversible inhibitors is that what whenever they actually bind and form a complex, whether that complex be the enzyme inhibitor complex or the enzyme substrate inhibitor complex, it is an irreversible formation of the complex. So notice that we have a one direction arrow here, and we don't have equilibrium arrows, which would suggest that the, um complex could break down backwards. But here we just have this one way era. And so notice down below. We're showing you how the molecule D I P f is an example of an irreversible inhibitor and so d I p f is the molecule di isopropyl faso florid, and its structure is shown right here and notice on the right. What we have is the enzyme that were pretty familiar with from our previous lesson videos. And it is Kimo trips. And and, of course, this is the active version of chemo trips. And and it turns out that the active version of chemo trips and has a searing amino acid residue in the active site that's critical for a proper Catala sis by chemo trips. Now notice that the irreversible inhibitor D I. P. F. Will actually react with this important Syrian residue. And it will form an irreversible complex here where notice that the irreversible inhibitor D I p f is cove innately bound here through this pink bond to the searing amino acid residue that is critical for kinda trips and to be active. And so notice here. Now what we have is an inactive Kimo trips and and because this is a stable Covalin bond here, that makes d I p f. An irreversible inhibitor, and it will essentially again completely inactivate Kimo trips and decreasing this particular enzymes activity. All the way down to zero. And of course, these side products here are also produced. And so in our next video, we'll be able to get some practice applying these concepts, so I'll see you guys there.
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Problem
ProblemWhich of the following statements about irreversible inhibitors is correct?
A
Irreversible inhibitors can only bind to an enzyme active site.
B
Dilution of the inhibited enzyme restores activity.
C
Irreversible inhibitors do not have to bind to the active site.
D
Increasing [S] restores activity to inhibited enzyme.
E
Initially, irreversible inhibitors will reversibly bind.
3
concept
Irreversible Inhibition
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So now that we've introduced irreversible inhibitors in this video, we're going to talk about suicide inhibitors, which are really just a specific type of irreversible inhibitor. And so suicide inhibitors are irreversible inhibitors that will partially mimic a substrate in the active site of an enzyme. But just like all irreversible inhibitors, ultimately they will end up irreversibly bound and stuck to the enzyme and activating it completely. And so suicide inhibitors initially are going to act just like a normal substrate would. And what that means is that these suicide inhibitors they actually require these normal ca Tallis ISS reactions to begin to bind to the enzyme. But ultimately, these normal catalytic reactions are going to proceed up to a point where the suicide inhibitor is going to remain co violently bound to the enzyme, just like all irreversible inhibitors. And so how exactly do suicide inhibitors differ from other irreversible inhibitors? Well, suicide inhibitors have to undergo some normal catalytic reactions because again they mimic a substrate, whereas other irreversible inhibitors don't necessarily have to undergo these normal catalytic reactions to end up irreversibly bound and stuck to the inside. And so this concludes our brief lesson on suicide inhibitors, and we'll be able to get some practice utilizing these concepts in our next video, so I'll see you guys there.
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Problem
ProblemA suicide inhibitor of an enzyme is one that:
A
Is reversible.
B
Is activated by one type of enzyme for the purpose of inhibiting a second type of enzyme.
C
Is competitive with the enzyme and inactivates the substrate.
D
Is competitive with the substrate and inactivates the enzyme.