Steps of glycolysis

- [Voiceover] So let's give ourselves an overview of glycolysis. and glycolysis is an incredibly important biochemical pathway. It occures in practically all life as we know it and it's all about taking glucose as a fuel and, in the process of breaking it up, lycing the glucose, glycolysis, breaking it up into two pyruvate molecules. Glucose is a six carbon molecule. Each of the pyruvates are three carbon molecules. In the process of doing that, you produce two ATPs net. It actually turns out that you need to use two ATPs and then you produce four. So you use two ATPs. That's often called the investment phase and we'll talk about that in a second. And then you produce four ATPs for a net of plus two ATPs and that's what we see right over here. You see a net of two ATPs being produced directly by glycolysis, and then you also have the reduction of NAD to NADH. Remember, reduction is all about gaining electrons, and over here, NAD, that's nicotinamide adinine dinucleotide, we have other videos on that, it's an interesting molecule, it's actually a fairly decent-sized molecule, we see this positive charge, but then we see that not only does it gain a hydrogen, but it loses its positive charge. It gains a hydrogen and an electron. You can think on a net basis it's gaining a hydride. Now a hydride anion's not going to typically be all by itself, but on a net basis, you can think about that's what's happening. And so it's gaining a hydrogen and an extra electron and so this, the NAD+, this is going to get reduced. That is going to get reduced to NADH. So this is getting reduced to NADH. And that NADH, it can then be oxidized in the electron transport chain. We'll study that later on when we think about oxidative phosphorylation, to produce even more ATPs. But on a very high-level, simple basis. Glucose being broken down in pyruvate, six carbons, three carbons each of these pyruvates, now there's other things attached to the carbons, and we'll see that in a little bit. Two ATPs net generated, and you have the reduction of two NADs to two NADHs, and those can be used later on to produce more ATPs. Now, glycolysis is typically just the beginning of cellular respiration. If oxygen is around, then you have these products, some of these moving into the mitochondria where you can have the citric acid cycle, Krebs cycle, and the oxidative phosphorylation occur. If you don't have oxygen around, then you're going to do anaerobic respiration, or you're going to go into fermentation. We'll talk about that in a future video, and that's really about figuring out what to do with these products, and especially replenishing your NAD+. Now that we have a very high-level overview of glycolysis, let's get a better appreciation for exactly what's going on. And whenever I look at these more detailed processes, the one thing to just appreciate is how much complexity is occurring in all of your cells right now. This is fairly abstract, to even imagine these things, but this is happening throughout your body gazillions of times, right now. This isn't something that is somehow distant from you. And it's also fun to appreciate, well how all of this was discovered by scientists. That's a whole other fascinating discussion. But the whole point of this video is just to give us an appreciation for the actual mechanism or the reaction by which it occurs. I'm not gonna go into the detailed organic chemistry mechanism. So over here, this is a glucose molecule over here, you see one, two, three, four, five, six carbons. And then the first step is, it gets phosphorylated and we have a whole video on the phosphorylation of glucose, and all of these steps are facilitated with enzymes. The phosphorylation is facilitated with the hexokinase. Kinase is a general term for an enzyme that either facilitates phosphorylation or dephosphorylates, it's dealing with phosphorylation, I guess you could say. And enzymes are all about lowering the activation energy. And the way that hexokinases do, or part of how they do it, is they involve the cofactor, a magnesium ion. And we've talked about that in other videos, how cofactors can help an enzyme lower the activation energy. And to do the phosphorylation, we use an ATP. So this is minus one ATP. So we are in the investment phase. But this reaction strongly goes from left to right, it's a coupled reaction that, phosphorylating the glucose, that requires free energy, but the ATP releases free energy you couple these reactions, it strongly goes from left to right. Now, and just to be clear what happened, this over here got replaced, or maybe I should say this over here got replaced with that over there. Just to keep track of what's happening. Now, another enzyme-catalyzed reaction, this one is actually an equilibrium, it can go both ways, but as we'll see, the right side or the things that are further into the glycolysis process, these are constantly being turned into further products, so their concentrations are going to go down, and so the reaction will tend to go that way. Although this particular reaction, going from glucose 6-phosphate to fructose 6-phosphate, this could be an equilibrium. But the enzyme that facilitates this, phosphoglucose isomerase, these are enzymes that help go from one isomer of a molecule to another isomer. And that's what's happening here. Instead of this oxygen being bound to this carbon, this bond forms with this carbon. So you have fructose, you have the five-carbon ring over here, or you have the five-element ring, you have four carbons in it, versus a six-element ring where right over here you have five carbons. So this bond goes to this carbon right over here and that's the main difference. And then you have another, very strong forward reaction, once again facilitated by ATP, and this is done by phosphofructokinase. It has the word kinase in it. And it's using up the ATP, you can guess what's going to happen. We're going to attach another phosphate group to the fructose 6-phosphate, and now you have two of these phosphate groups. So this hydrogen right over here is now replaced with another phosphate group. And once again it's facilitated by the magnesium cofactor, it helps stabilize some of the negative charge associated with the phosphate groups, we talk about that in other videos. But the important thing is, it uses another ATP. We're still in the investment phase, negative one ATP. And every time I look at this it's just fascinating that all of this stuff is happening in your cells as we speak. In fact, in order for me to speak this has to happen, because my body needs to take glucose and come up with some energy to turn into ATPs so that my muscles can actually move and I can actually inhale and exhale and all the things that I need to do for speech. So appreciate what's going on over here. Now the next step we talk about, the whole process of glycolysis is lysing glucose. And over here this is derived from glucose and some phosphates, and the next step, we're actually going to break it up. And we're going to break it up using the enzyme fructose biphosphate aldolase. Aldolase enzymes facilitate the aldol reaction. And this one, the aldol reaction could be to merge two molecules or in this case, we're going to break them up. And we break them up into two three-carbon chains. Now these two three-carbon chains, glyceraldehyde 3-phosphate, and this character right over here, they can be converted between the two with another isomerase, this triosephosphate isomerase right over here. So at this point in glycloysis, we can think of ourselves as really having two of these. So let's say two times glyceraldehyde 3-phosphate. So as we go further on, just imagining this happening twice for every glucose molecule. And any time you get confused, I encourage you to pause the video. See how these pieces and these pieces put together, can form that over there. So now we have another reaction, it's facilitated by a dehydrogenase. Dehydrogenases usually are involved in this case, this is the reduction of NAD. We saw that in the overview video. So NAD is being reduced. And this can be used, this NADH later on can be used in the electron transport chain to potentially produce some more ATP, but in that process we also add another phosphate group to the glyceraladehyde 3-phosphate. So you see this phosphate group right over here that wasn't there before. And actually this right over here is I should have arrows on both sides, this right over here, that reaction could actually go both directions. Actually, that reaction can as well. And then, we are now going to be in the payoff phase. So this right over here, we're starting with this molecule that has these two phosphate groups, and then using the phosphoglycerate kinase, we're able to pop one of those phosphate groups off and in the process, produce ATP. Now we might want to say plus one ATP, but we have to remember, this is now happening twice. Cuz we had two of those glyceraldehyde 3-phosphates, so now we could say, if we're talking about this happening twice, plus two ATPs. We are now in the payoff phase. Then you have, facilitated by the phosphoglycerate mutase, a mutase is a class of isomerases. I have trouble saying that. That'll take a functional group from one place to another, or take one part of a molecule to another part, and you see this phosphate group moving on from this carbon to the middle carbon. And so that's what that's doing. Then we use an enloase to get over here and then the pyruvate kinase, and here the kinase is going to be used to dephosphorylate this molecule right over here, and it gets us to the way I've drawn it is pyruvic acid, since I've drawn the hydrogen here, and if the hydrogen is let go and this oxygen hogs the electron, we would call this pyruvate. And this is considered to be the end of, I guess you could say, mainstream glycolysis. But what happened, and I don't want to glaze over what happened over here, this ADP got converted to another ATP, but it's going to happen twice. So this is another plus two ATPs. So hopefully you see the investment phase, we use an ATP right over here to phosphorylate the glucose, we use another ATP right over here to throw that second phosphate group on what was the fructose 6-phosphate, but then we get the payoff phase. So we're able to produce this NADH, and this is actually going to be two NADHs, because everything here's going to happen twice now, we can assume that this character over here also gets converted to a glyceraldehyde 3-phosphate, and now we've produced two ATPs, cuz this is happening twice, and we've produced two ATPs right over there. So hopefully everything we talked about in the beginning actually makes sense.