Learn about covalent modifications and how they change enzyme behavior. Learn about post-translational modifications like methylation, acetylation, and glycosylation. Understand zymogens, the inactive proteins that need covalent modification to activate. Finally, discover suicide inhibitors, the enzyme inhibitors that permanently bind their target.
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- Does enterokinase activate trypsinogen to trypsin by phosphorylating it, since it is a kinase?(7 votes)
- Though we are conditioned to think 'phosphate transfer' when we see the word kinase, this is a historical name given to this enzyme that doesn't reflect its chemical mechanism (named by none other than Ivan Pavlov of classical conditioning fame). Many like to use 'enteropeptidase' to refer to this enzyme instead, because it prevents this confusion. Actually, enteropeptidase is a serine protease, which is a type of enzyme that hydrolyzes peptide bonds with the help of a serine reside in the enzyme's active site.(23 votes)
- Wouldn't Mg2+ or Flavin just be considered catalysts, and not enzymes? I always thought that enzymes were just catalysts that were proteins. I guess I was wrong. What makes an enzyme different from a catalyst?(6 votes)
- Mg and Flavin are cofactors, enzymes use them as helpers to make the reaction go. you are correct, all enzymes are proteins but not all proteins are enzymes.
what makes a catalyst different from a cofactor then?- A catalyst is part of a chemical reaction that does not get used up and lowers the activation energy. A cofactor is a helper for an enzyme to make the reaction go. Without it, the enzyme can not do its job (remember the enzyme is what lowers the activation energy for a reaction), so an enzyme is a catalyst thats a protein essentially.(8 votes)
- what is the purpose of a suicide inhibitor?(2 votes)
- Suicide inhibitors are another class of inhibitors called non-reversible inhibition. One common use of these are in drugs. If there exists an enzyme unique to the bacteria we are trying to fight, we could develop a suicide inhibitor to permanently prevent that enzyme from functioning correctly.
One pretty cool example of a suicide inhibitor is actually aspirin. Aspirin irreversibly binds to Cyclooxygenases 1 and 2, which produce prostaglandins (responsible for pain). So the only way the body can produce more prostaglandins is to make new enzymes.(7 votes)
- At2:00, why would acetylation of the lysine molecule mean that it can no longer carry a positive charge? There are still two un-shared electrons on that N atom, why could it not still bond to another hydrogen proton to give it a positive charge?(2 votes)
- Also, acetylation of the lysine molecule at the nitrogen position affects how accessible the two lone pairs are. Since the acetyl group is an electron-withdrawing group, that group will pull electron density from around the nitrogen towards it; this would make it more difficult for the nitrogen to offer its lone pair for bonding to a proton. Thus, that part of the lysine molecule is less effective at behaving as a base/proton acceptor.(2 votes)
- At0:38, a box comes up and says that "inorganic metals (MG2+) and small organic substances act as.....co-enzymes." Is that always the case with non-proteins? In other words, are all non-proteins co-enzymes regardless of whether or not they are organic or inorganic?(1 vote)
- No, co-enzymes are pretty specific in their role. Ions like Na+ and K+, which are non-proteins, act to maintain blood pressure and sustain a cell membrane potential.(2 votes)
- (0:30) So if magnesium and flavin are both enzymes, is magnesium not a cofactor and flavin not a coenzyme? Can something be both an enzyme and a cofactor/coenzyme?(1 vote)
- In case anyone reads this in the future and they are curious -- magnesium and flavin are cofactors with the former being an inorganic cofactor and the latter being an organic coenzyme. These are necessary for the enzymatic process to continue. Without them, you have an apoenzyme which is inactive.
It's a little strange to refer to them as enzymes. As you know, Mg and flavins have several uses in the world but the same cannot be said about a very specific protease which is an enzyme.(2 votes)
- What is a Chrodues Enzyme @2:59?(1 vote)
- I had thought suicide inhibitors were called suicide inhibitors because the enzyme inadvertently participates in the inhibition? The enzyme believes the suicide inhibitor is a substrate, attempts to catalyze the reaction, but ends up covalently bound to the inhibitor. Like how penicillin works.(1 vote)
- [Voiceover] So today we're gonna learn about covalent modifications to enzymes. But first, let's review the idea that enzymes make reactions go faster. And looking at a reaction coordinate diagram you notice that enzymes do this by lowering the reaction's activation energy. Also, before we talk about covalently modified enzymes, I want to remind you that not all enzymes are proteins. And often, when we think of enzymes we think of proteins, which are amino acid polymers with primary, secondary, tertiary, and quadrinary structures. But there are also many different kinds of enzymes that aren't proteins. Inorganic metals, like magnesium, or small organic molecules, like flavin, can also act as enzymes. But for the purposes of this discussion we're going to focus on the proteins. And to be clear, when we say covalent modifications, we refer to modifications to a protein that involve forming or breaking covalent bonds. Now there are tons of different covalent modifications that we can observe. So I'm only gonna touch on a select few to get the point across. And the first category of covalent modifications I want to talk about are small post-translational modifications. Now, when I say translation, I'm referring to the process of translation where amino acid polymers are synthesized. And when I say post-translation, I refer to events that take place after that initial synthesis. Now when I say small, all I'm referring to are modifications that involve small functional groups being added or removed from an enzyme. And again, there are many different types of these but I'm just gonna touch on three. So methylation is a modification of a protein that involves the addition of a methyl group, or CH3, to a protein. Acetylation involves the addition of an acetyl group. And glycosylation involves the addition of a sugar molecule. And these are just three examples of a huge list. And these modifications, although small, can have pretty significant impacts on protein as a whole. And to discuss this, I want to mention the example of acetylation of a lysine residue on a protein. So as you many know, lysine is an amino acid that has an extra amino group on its side chain that can act as a base and carry a positive charge. If we were to acetylate this lysine residue and add an acetyl group to the amino and nitrogen, which is a covalent modification, the electron withdrawing effect of the acetyl group will prevent that nitrogen from carrying a positive charge, and modify the behavior of that amino acid. The loss of that positive charge can change a few properties of the amino acid, including changes to the lysine's acidity and basicity, since it can no longer exchange protons, as well. And it will also influence lysines electrostatic interactions with other charged molecules, since it's lost that positive charge. So even a small modification, like the addition of a cell group, can have significant impacts on the protein overall. Moving on, I want to discuss another way in which covalent modifications of enzymes is relevant. And that's in reference to zymogens. Now a zymogen is an inactive form of an enzyme that requires a covalent modification in order to become active. And a big example of these zymogens in biology are the digestive enzymes of the pancreas releases so that you can digest food. One of the enzymes of the pancreas releases is called trypsinogen, which is a zymogen as indicated by the ogen suffix. Now this is an inactive form of a chrodeus enzyme that is shipped to the intestine. And once in the intestine, it's covalently modified by an enzyme called enterokinase which converts it to its active form trypsin. Now this is to prevent trypsin from breaking down proteins that we need in the pancreas since it's inactive at that point as trypsinogen. And only allows it to break proteins down in the intestine after it's encountered enterokinase. Notice how you can distinguish zymogens from their active form by their name, zymogens have ogen added to the end of them. Now the last example of covalently modified enzymes that I want to discuss is the subject of suicide inhibition. Now, when we think of enzymatic inhibition we usually think of competetive, non-competetitve, and uncompetetive inhibitors which follows certain patterns in terms of their effects on enzyme kinetics. But there's another type of inhibitor that's a little different, and this is the suicide inhibitor. Suicide inhibitors covalently bind the enzyme and prevent it from catalyzing reactions. And what's interesting is that since these inhibitors form covalent linkages to the proteins, they rarely unbind, which is why we call them suicide inhibitors. Since after they bind, that's it for them. And this is what distinguishes this type of inhibitor from the other three that you might be familiar with. So, what did we learn? Well, we talked about three very different things today that all have to do with covalent modifications to enzymes. First, we talked about small post-translational modifications, like methylation, acetylation, and glycosylation. Second, we discussed zymogens, inactive proteins that require covalent modification to become active. And finally we talked about suicide inhibitors, which are enzyme inhibitors that permanently bind their target.