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Enzyme cofactors and coenzymes

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- [Voiceover] We've already spent a couple of videos talking about enzymes, and what I want to do in this video is dig a little bit deeper and focus on some actors that actually help enzymes. And just as a reminder, enzymes are around to help reactions to proceed, to lower their activation energies, to make the reactions happen more frequently or to happen faster. Now, we've already seen examples of enzymes, and just to frame things in our brain properly, sometimes in a textbook you'll see an enzyme like this, you'll see a drawing like this. And people will call this the enzyme, they'll call this the enzyme, and then they'll call this right, they'll say okay, and it's acting on some kind of a substrate right over here, it's going to do something to that. And this is nice for a very abstract, textbook idea of a substrate locking into an enzyme like this, but this isn't actually what it looks like in a biological system. We have to remind ourselves, when people talk about enzymes they're talking about proteins. Now there are these kind of RNA enzymes called ribozymes but the great majority, when we're talking about enzymes, we tend to be talking about proteins. And we spent a lot of time talking about how proteins are these structures, there's polypeptides, and all the side chains of the various amino acids fold the proteins in all sorts of different ways. So a better drawing for something like this would be this protein that's all folded in different ways, maybe has some alpha helices here, maybe it has some beta sheets right over here. It's all this kinda crazy stuff right over there. And then the substrate might be some type of a molecule, that is it gets embedded in the protein. And you see some examples right over here. This is actually a hexokinase model and you see, at least you can see a little bit of the ATP right over there, and it's a little harder to see the glucose that's going to be phosphorylated. And this reaction is being facilitated by this big protein structure, the hexokinase. Now, what we're going to focus on in this video is that, when we talk about an enzyme, and we're talking about proteins, we're talking about a chain of amino acids, but there's often other parts of the enzyme that aren't officially proteins. And we even saw that when we talked about hexokinases, when we talked about the phosphorylation of glucose, we said hey, the way that it lowers the activation energy is you have these positive magnesium ions, these positive magnesium ions, that can keep the electrons in the phosphate groups a little bit busy, draw them away, so that this hydroxyl group right over here can bond with this phosphate and not be interfered with these electrons. Well these magnesium ions right over here, they aren't officially part of the protein. These are what we call cofactors. So you might have a cofactor right over there that latches onto the broader protein to become part of the enzyme, and you actually need that for the reaction to proceed, it plays a crucial role here. So another drawing in the textbook, you'll see something like this, or even, they'll draw, they'll say okay, in order for this reaction to proceed, yes, you need the substrate, but you also need the cofactor. The cofactor. And once again, it sounds like a fancy word, but all it means is a non-protein part of an enzyme. It's another molecule or ion or atom that is involved in letting the enzyme perform its function that it's not formally a part of an amino acid or part of a side chain or part of the protein, but it's another thing that needs to be there to help catalyze the reaction. We saw that with hexokinase, you had magnesium ions that the complex picks up. And this is why, when people talk about your vitamins and minerals, a lot of the vitamins and minerals that you need, they actually act as cofactors for enzymes. And so you could even see it in this drawing over here, at least based on what I read these are the magnesium ions in green right over here, and these are cofactors. These are cofactors. So cofactor, non-protein part of your actual enzyme. Now, we can subdivide cofactors even more. We can divide them into organic cofactors and inorganic cofactors. So if you have cofactors, we've seen an inorganic cofactor, a lot of these ions, you'll see magnesium ions, you'll see sodium ions, you'll see calcium ions, you'll see all sorts of things acting as cofactors, often times to distract electrons, or to keep them busy so that electrons can proceed. But you can also have organic ones, you can also have organic molecules. Remember, organic molecules, these are just, they'll involve carbon, they have chains of carbons and other things. And cofactors that are organic molecules, we call them coenzymes. Coenzymes. And there's a bunch of examples of coenzymes. This right over here is the enzyme lactate dehydrogenase and it has a coenzyme, and this coenzyme you are going to see a lot in your biological careers, NAD, right over here. Notice, this isn't just an ion, it is an entire molecule. It has carbon in it, that's why we call it organic. And it is not formally protein, it's not part of the amino acids that make up the protein, so that's what makes it a cofactor, and since it's an entire organic molecule, we call this a coenzyme. Coenzyme. But like any cofactor, it plays a role in actually allowing the enzyme to do its function, to facilitate a reaction. And this particular coenzyme, NAD, which you're going to see a lot, it helps facilitate the transfer of hydride ions. Hydride ions never, or very seldom, exist by themselves, but it's a hydrogen with an extra electron, so it has a negative charge. So it allows the transfer of this group from a substrate or to a substrate, and that's because NAD can accept a hydride anion right over here and become NADH. And if you want to see its broader structure, it's actually quite fascinating. I'll probably do a whole video on NAD because in so many textbooks growing up I just saw NAD and NADH and I'm like what is this thing? And it's a fascinating molecule. So what it can do is it can actually pick up the hydride anion right over here at this carbon, you can actually form another bond with the hydrogen, and I'll do that in a future video, I'll show the mechanism for it. But it's a pretty cool molecule and I like to actually look at this molecule and remember, the whole focus of this is coenzymes, but we see these patterns throughout biology because the name, nicotinamide adenine dinucleotide exactly describes what it is. Nicotinamide, right down here, that is this piece of the molecule, and this is the part that can accept a hydride or let go of a hydride, so you could say this is the active part of the molecule. Adenine, our good old friend, we've seen adenine in DNA, in RNA, in ATP, so this is our good old friend adenine, right over here. And it says dinucleotide, cause we actually have two nucleotides paired together, their phosphate groups are tied together. And there's a couple cool ways to think about this. You have an adenine right over here, you have a ribose, you have a phosphate group. If you just looked at this piece, right over here, if you looked at this right over here, this is your building block, or this could be a building block, of RNA, if you have an adenine right over there. And if you include, let me undo this, if you include all of this, this right over here, this is ADP, well the reason why it's called dinucleotide is you can also divide it the other way. You can say, alright you have one nucleotide that has nicotinamide right over here, so that's one of the nucleotides, and then the other nucleotide is right over here, the one that involves adenine, that's why it's called dinucleotide. So hopefully this makes NAD less of a mysterious molecule, we'll see it in the future, but I like to look at it because it's got all these patterns, it's got all these components that you see over and over again, and you see it in ATP, you see it in RNA, over and over again. But this isn't the only cofactor or coenzyme. There are many many others, in fact when people say take your vitamins and your minerals, that tends to be because they are cofactors. Vitamin C is a very important cofactor to be involved in enzymes that, well I won't go into all of the different things that it can do. These are two different views of vitamin C, a space-filling model and this is a ball-and-stick model right over here of vitamin C. Folic acid, once again, two different views, but these are all coenzymes, they all work, you know if you have a protein right over here that you know it's all this really complex structure, maybe you have some substrates, but to help facilitate, let me do the substrates in a different color, so maybe you have some substrates, so these are the things that the enzyme is trying to catalyze the reactions for. But then you could have some ions, which would, you know, you could kind of view these as you would view these, you would view the ions as cofactors, and you could have organic cofactors, like the vitamin C, or other things that we talked about that are also involved and help facilitating the mechanism, or help facilitate the reaction. And once again, sometimes it might be to help stabilize some charge, sometimes it might be to be an electron acceptor or donor, or a whole series of different things. They can actually act as part of the reaction mechanism.