Seeing how an inhibitor can "compete" for an enzyme with the intended substrate.
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- What is the origin of the word "substrate?" Isn't that a strange name? Why isn't it something more understandable like "reactant" or reaction component?(5 votes)
- It is Latin: substratum, it translates "sth. spread below" like soil or a growth medium. In enzyme reactions the substrate is the base substance for the generation of the product.(26 votes)
- So I understand the basics of competitive inhibition, the inhibitor attaches to the enzyme which results in the substrate not being able to attach. What I didn't get as clearly is whether the inhibitor will detach like the substrate does after the reaction. Or does the enzyme just end up being permanently unable to catalyze reactions?(11 votes)
- >What I didn't get as clearly is whether the inhibitor will detach like the substrate does after the reaction.
This is answered by whether the inhibitor is reversible one or an irreversible one. My understanding is that in the case of irreversible inhibitors, the inhibitor may form a covalent bond (or a strong noncovalent one) with the enzyme, thus altering its chemical structure and inhibiting its expected behaviour. Therefore, irreversible inhibitors are sometimes used in pharmaceutics to inhibit enzymes such as the bacterial enzymes.(7 votes)
- Do all enzymes only have 1 active site?(8 votes)
- No, some bigger enzymes have different active sites which allows them to catalyze more reactions.(11 votes)
- Is Inhibition ever useful?(5 votes)
- Inhibition could be helpful at times because it prevents the excess of products the body doesn't need. Over-accumulation of products are harmful to an organism therefore by inhibiting the joining of a substrate to an enzyme you reduce that accumulation.(12 votes)
- so is there always a chance that when an enzymatic reaction is taking place then some competitor would be there to compete with the substrate or only limited amount of reactions suffer through this phenomenon(i.e competitive inhibition)?(3 votes)
- Both. Let me explain.
There are some enzymes, which work in many pathways. They have relatively poor substrate specificity and this is important, because it's function requires it to do transform so many chemically different substrates into metabolites. Eg: The cytochrome p450 in liver, alcohol dehydrogenase. The former is a very important enzyme system, which plays a role in metabolising (a fancy term for "acting upon") a wide variety of foreign substances, which include drugs and toxins. These reactions are the main mechanism of our body to fight drugs, and competitive inhibition is important here when we want to design drug therapies, because if we give two drugs both of which are acted upon by this enzyme, then they shall compete for its binding, and a result both will be metabolised slowly (in relation to if each was given independently). Alcohol dehydrogenase metabolises alcohols (Duh!), and hence is the reason why methanol is poisonous. IT converts it into the more poisonous methanoic acid. For a patient of methanol poisoning, the main therapy includes giving ethanol (yeah, awesome, I know!) so that it acts as a competitive inhibitor, preventing methanol from forming the harmful metabolite.
The more substrate-specific enzymes, as you would expect, do not usually have complications pertaining to competitive inhibitors.(6 votes)
- What happens to the enzyme and inhibitor after they bind? Is the enzyme ruined? Does the inhibitor ever separate?(4 votes)
- It depends whether inhibitor in question is reversible or irreversible.
in case it is reversible, inhibitor will detach after some time and leave enzyme unaffected.
Otherwise, inhibitor will stay forever attached to it and enzyme is 'ruined'.(3 votes)
- What are some examples of competitive inhibition reactions that take place in the body?(3 votes)
- An example of competitive inhibition could be malonic acid which competes with succinate for active sites of succinic dehydrogenase, an important enzyme in the Krebs cycle.
Another Example: Ethanol is metabolized in the body by oxidation to acetaldehyde, which is in turn further oxidized to acetic acid by aldehyde oxidase enzymes. Normally, the second reaction is rapid so that acetaldehyde does not accumulate in the body. A drug, disulfiram (Antabuse) inhibits the aldehyde oxidase which causes the accumulation of acetaldehyde with subsequent unpleasant side-effects of nausea and vomiting. This drug is sometimes used to help people overcome the drinking habit.(3 votes)
- I read somewhere that inhibitors “fit into the Active Site, but remain unreacted since they have a different structure to the substrate”. But this cant be true can it? Methanol for example, is a competitive inhibitor, but it does “react”; the enzyme breaks it down further to something dangerous (cant recall the name). Inhibitors don’t just “sit” there, do they?
Also, why is methanol considered an inhibitor? What exactly does it inhibit if the enzyme still “works”?(3 votes)
- Inhibitors does not have to bind to the active site in order to inhibit enzyme. If they are allosteric they bind some external site and change shape of enzyme - deform active site - which is now malfunctioned and unable to bind substrate.
Well, if enzyme still works after methanol binding to it, it means that methanol is reversible inhibitor.
Since methanol binds to active site, it physically prevents substrate to bind to enzyme. However, after some time, methanol detaches and leaves active site unchanged and open to substrate.
Methanol was temporary barrier, not permanent.(1 vote)
- so in both cases the enzyme becomes useless or does it recover?(3 votes)
- "Enzymes are not reactants and are not used up during the reaction. Once an enzyme binds to a substrate and catalyzes the reaction, the enzyme is released, unchanged, and can be used for another reaction"
- Can one enzyme have more than one active site?(3 votes)
- We've already seen that an enzyme helps catalyze a reaction, so let's say this right over here, this is our enzyme, and we have our substrate, and it goes and it binds to the active site, to the active site of the enzyme, so let's say it binds right over there on the enzyme we call it the active site where the substrate binds and then the enzyme catalyzes a reaction; maybe it breaks up this substrate into two smaller molecules. And so after the reaction, the enzyme, whoops. After the reaction, the enzyme is unchanged, but a reaction has been catalyzed. We now have the substrate being broken up, in this case at least, into two smaller molecules. Maybe I'll draw them. That's one of them. And this is the other one right over here. So they just came from the active site. Once the reaction is catalyzed, they don't have the affinity to the active site anymore and they break off. So this enzyme has just catalyzed this reaction. What I wanna talk about in this video is how this might be inhibited, and specifically how it might be inhibited competitively. So we're gonna talk about competitive inhibition. So competitive-- Let me write it over here. Competitive inhibition. Inhibition. So the classic case of competitive inhibition: if there's some molecule that competes for the substrate at the active site, as we'll see this isn't the only form of competitive inhibition, but this is the one that you will most typically see in a textbook. So that's our enzyme again. So that's our enzyme. And we've already seen that this is right over here where I'm circling, that is the active site. Active site. And if the molecule, the intended substrate I guess you could say, gets to it and we're gonna have this first scenario up here. But in classic competitive inhibition, or at least the version I'm just gonna show you right now, you could have another molecule that let's say it looks something like this that can compete for the active site and if it gets to the active site first, so if it gets there first, let me show what's going to happen, so then we have our enzyme, we have the other molecule, not the intended substrate binds to the active site first. Well now the intended substrate, the one for which the enzyme catalyzed the reaction, isn't able to bind and the reaction isn't going to happen. And you can see very clearly that they are competing for the enzyme, and in this case, they're competing for the active site. Now this isn't the only form of competitive inhibition. Another form of competitive inhibition is allosteric competitive inhibition. Let me write this down. So you have allosteric. Allosteric competitive inhibition. Now I'm having trouble writing. Inhibition. And an allosteric site is a site other than the active site. But in allosteric competitive inhibition or competitive allosteric inhibition, however you wanna say it, you have a scenario where the competitor doesn't bind to the active site but binds to a site that is not the active site, an allosteric site you could say. So in that one, the competitor, maybe might bind here, so that's clearly not the active site. So maybe the competitor looks something like that. It didn't bind to the active site, but by binding there, the active site can no longer bind to the intended substrate, so you have the same effect. You have the same effect right over here where this thing isn't going to bind. But if this thing binds first... So let me draw that scenario. So if the intended substrate binds first, then the competitor can't bind. So in this scenario, if the substrate is able to get to the active site, well then the competitor can't bind, so once again, they're competing. So I'll draw the competitor up here. So then the competitor, whoever gets to it first gets the enzyme. So in this situation, the competitor's not going to bind. So that's true of whether you're talking about competitive inhibition where they're competing for the active site, if the competitor gets there first, the intended substrate isn't gonna get there, the reaction isn't going to be catalyzed. Or if the intended substrate gets first, then the competitor's not going to be able to get there. In fact it could have been this situation where because the substrate got there first, the competitor isn't going to be able to bind to the active site. When we're talking about allosteric competitive inhibition, we're still competing for the enzyme. Only one's gonna get it. If one gets to the enzyme first, then the other one's not going to be able to get there. They are competing for the enzyme, but the competitor, the non-substrate, is just acting at an allosteric site. By binding to an allosteric site, it changes the conformation of the enzyme so that the active site no longer binds to the substrate. And I wanna really emphasize this point because when I first learned this, I said: "Oh!" And it's often sometimes confusing, even some things you'll read on the Internet, that they'll say that this allosteric type of inhibition, they'll call this non-competitive 'cause you're not competing for the active site, but that is actually not the case. In non-competitive inhibition, and I'm gonna do the whole next video on non-competitive inhibition, in non-competitive inhibition, the inhibitor right over here can bind regardless of whether the substrate has bound or not, but when the inhibitor does bind, it prevents the reaction from moving forward, it changes the conformation of the protein so it no longer catalyzes the reaction. So non-competitive, they both can bind, but if the inhibitor is there, the reaction isn't going to proceed. In competitive inhibition, whether we're talking about allosteric or non-allosteric competitive inhibition, only one of the substrate or the inhibitor is going to be able to bind. They are competing for the enzyme.