Irreversible Inhibition - Video Tutorials & Practice Problems
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concept
Irreversible Inhibition
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5m
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Video transcript
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 naught all the way down to 0. Now these irreversible inhibitors can form stable covalent bonds with the enzyme and because these are such stable covalent bonds, they are very, very difficult to break which is why these bonds are pretty much irreversible. And because irreversible inhibitors pretty much stop and inactivate the enzyme activity, they're also known as inactivators. And so inactivators and irreversible 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 to 1 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 inactivators are often powerful poisons. However, they can also be used by doctors as drugs in 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 inhibitor complex. Here, we're just showing you one version, but it can actually bind to both the free enzyme as well as the enzyme substrate complex. But really the main point of irreversible inhibitors is that 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 complex could break down backwards. But here we just have this one way arrow. And so, notice down below, we're showing you how the molecule DIPF is an example of an irreversible inhibitor. And so DIPF is the molecule diisopropylphosphofluorate and its structure is shown right here. And notice on the right what we have is the enzyme that we're pretty familiar with from our previous lesson videos and it is chymotrypsin and, of course, this is the active version of chymotrypsin. And it turns out that the active version of chymotrypsin has a serine amino acid residue in the active site that's critical for, a proper catalysis, by chymotrypsin. Now, notice that the irreversible inhibitor, DIPF, will actually react with this important serine residue and it will, form an irreversible complex here where notice that the irreversible inhibitor, DIPF, is covalently bound here through this pink bond to the serine amino acid residue that is critical for chymotrypsin to be active. And so notice here now what we have is an inactive chymotrypsin. And because this is a stable covalent bond here that makes DIPF an irreversible inhibitor and it will essentially, again, completely inactivate chymotrypsin, decreasing this particular enzyme's 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
Problem
Which 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
Video duration:
1m
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Video transcript
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 catalysis 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 covalently 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 enzyme. 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
Problem
A 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.