Understanding the Krebs Cycle Process

Alright Ninja Nerds, in this video we're going to talk about the Krebs cycle. So, you can also call it, you know, the tricarboxylic acid cycle, you can call it the citric acid cycle, so there is other names for it. It was actually founded and developed by the guy named Hans Krebs. That's where it came from. Okay, so now, when we go through the Krebs cycle, we've already gone over in great detail, we've already gone over the glycolysis pathway, we've actually... gone over all the glut transporters. We've gone over the glycolysis pathway of converting. What is this molecule right here? This is glucose right here. We've converted glucose into pyruvate. And how many pyruvates have we actually made? Technically we made two of these, right? Because we split the six carbon fragment into two three carbon fragments. So we've actually made two pyruvates. And during that process, you guys already know that we generated two NADHs and two net ATP. And then, you know that we've already gone into detail whenever there's oxygen present, we can take this pyruvate, bring it into the mitochondria, and we can transition it, right? We can get ready to transition to the Krebs cycle. And in that transition step, or that preparation step, what did we do? We added a coenzyme in. into this reaction right and then what else did we do we generated two NADHs and we produced two CO2s by decarboxylation and that was done through this whole pyruvate dehydrogenase complex with the E1 E2 and E3 we already gone up we already went over that in great detail and all the mechanisms. Now we're going into this next thing, which is the Krebs cycle. So we formed acetyl-CoA from the transition step, right? This molecule right here is our acetyl-CoA. Now what we're going to do is we're going to convert this acetyl-CoA, we're going to fuse it with this four carbon fragment right here. This four carbon fragment is actually referred to as oxaloacetate. So again, this guy right here is called, I'm going to denote it. I'm going to abbreviate it OAA. Oxaloacetate is going to combine with the acetyl-CoA. When these two substrates combine, they fuse together in the presence of this enzyme. talk about this enzyme in a second. But OAA is a four carbon structure combining with a two carbon structure. And again, what is this red structure coming off of the acetyl-CoA? That's the coenzyme A. When this acetyl-CoA and when this OAA combine with this enzyme, they form a six carbon molecule. Look, one, two, three, four, five, six. What is this molecule called? This is called citrate. You know what's really interesting? Unisitrate is Krebs'starting substrate for making oxaloacetate. What did I just do? I gave you guys a little quick mnemonic to be able to remember all of this. So it's an easier one to be able to do. Okay, so how do I remember? Again, oxaloacetate and acetyl-CoA come together in the presence of this enzyme to form citrate. And I like to remember this. Citrate is Krebs'starting substrate for making oxaloacetate. What is is for? Is is for isocitrate. So let's get all these intermediates out of the way. Just an easy way to be able to remember them because that's what we long for. All right? Sometimes you can just get it out of the way, the memorization, right? Krebs is for alpha-ketoglutarate. I might refer to it as AKG whenever you guys see it like that. Starting is for succinyl-CoA. Succinyl. CoA. Substrate is for succinate. This is succinate. 4 is fumarate. And then the last one is making which is going to be malate and the last one is oxaloacetate. So again it goes citrate is Krebs starting substrate for making oxaloacetate. Just a little quick mnemonic. would help out to just memorize you know the basic intermediates now that we've done that really there's nothing crazy else that we have to know other than just the regulatory steps and what's happening in between okay cool so let's do that now that we know the intermediates let's focus on the enzymes and and what's produced and what's happening in each step. So acetyl-CoA and OAA, or oxaloacetate. When these two are fusing, there's a special enzyme. And what is this enzyme doing? It's forming citrate, it's synthesizing citrate. So what would that enzyme be called? You call it citrate. Synthase. So there's a citrate synthase enzyme. This citrate synthase, what is he doing? He's taking the oxaloacetate in one part, taking the acetylcholine in the other part, fusing them together and making citrate. Now the question is, this enzyme is extremely very highly regular. So it's going to control this step. So acetyl-CoA going into citrate with oxaloacetate, this is not a reversible step. This is a one-way reaction. So what does citrate synthase have to be regulated by? Okay, it's going to go on and on what you guys are going to see throughout a series these biochem videos. Think about this. If our body is having a lot of metabolism, so it's occurring a lot, a lot of metabolism, a lot of Krebs cycle, a lot of electron transport chain activity, I'm making a lot of ATP. If I'm making a lot of ATP, do you think I'm going to want to keep having the Krebs cycle going on, making more NADHs and FADH2s? No, because I already have too much of it. This is going to inhibit it. It's going to allosterically inhibit this enzyme. Same thing. In the Krebs cycle, you'll see... that will generate a lot of what's called NADHs that you see here. NADHs, if there's too many of them, it's also basically telling this enzyme, there's a lot of energy supply within the cell. We don't need any more. Shut down. Don't do this anymore. Okay, then we have another one, citrate himself. You know whenever there's actually too much citrate, citrate can actually come back and inhibit this enzyme. So citrate himself. can come back and inhibit this enzyme. So a citrate can say, okay, there's way too much of me. Because generally, what's going to happen when you make citrate? It'll automatically get converted into isocitrate, generally. Some of this citrate can also get converted into the basic units for fatty acids called malonyl-CoA. that but generally it should be progressing somewhere it shouldn't be building up when it's building up it's letting the citrate synthase know don't make any more of me stop working and then there's another one he's all the way down there though it's called called succinyl CoA. So succinyl CoA is also an allosteric inhibitor. He's just a little bit more downstream and he's just telling this enzyme, hey, before you even think about making citrate, there's already too much of me. So shut down and stop making more citrate and making more of me, making more NADHs, more ATP, just stop doing that. And these are generally the main allosteric regulators of this citrate synthase. Now what would be a stimulator? We've already talked about this so many times, but it's... It's a good way to keep continuously reviewing. ATP gets broken down into what, guys? It gets broken down into ADP and inorganic phosphate. If you're breaking down a lot of ATP, you're going to build up a lot of ADP. And this is going to signify that you are actually not having a lot of ATP within the cell. If there's not a lot of ATP in the cell, that's not good because ATP is needed for transport mechanisms, for metabolic pathways, for DNA synthesis, so many different things, ion channels. So ADP... would be a very powerful allosteric stimulator of this enzyme. It would let this enzyme know, hey, there's not a lot of ATP. You need to continue to keep going through the Krebs cycle, making more NADHs and FADH2s and make more ATP. So that would be that guy. So generally, this is how we're going to allosterically regulate this googly-eyed enzyme. Okay, because this googly-eyed enzyme is involved in this step right here, converting the acetyl-CoA into citrate. Very, very highly regulated step. Okay, so we're done with that one. Okay, so now we got this Betty White enzyme. Okay, this Betty White enzyme with the perm going on is converting citrate, which is a six carbon molecule into what? Okay, one, two, three, four, five, six. It's still six carbons. So what's really happening? It's just an isomerization reaction. And isomerization reactions, all you're doing is you're just shuffling around the hydrogens and the carbons, but there should still be the same number of carbons and hydrogens and oxygens in this guy as there is carbons, hydrogens, and carbons. and oxygens in this guy. So it's just shuffling things around. Not a crazy crucial step, but the enzyme controlling this step, as you guys can see, is doing what? It's able to move in the reverse direction. So whenever there is too much isocitrate, you can convert it back into citrate. It is possible. And it actually does happen, and you'll see this whenever we talk about this in fatty acid synthesis. But the enzyme that's controlling this is called aconitase. A-C-O-N-I-T-A-S-E. Okay, aconitase enzyme. So there's, you know, just because it's not controlling and it's not highly regulated and is reversible doesn't mean that this enzyme isn't important. You know there's a rat poison? Within rat poison there's a chemical that's present called fluoroacetate. And what happened? What happens with this fluoroacetate is it's kind of acting like acetyl-CoA. You know, acetate is just basically another fancy word for saying it's a two-carbon structure. All it has is just a fluorine attached to it. So it's going to get actually converted. It's going to act like fluoroacetate. So you know how you're going to have acetyl-CoA here? You're going to have this fluorine. acetyl-CoA which gets converted into fluorocitrate and that fluorocitrate binds on to the aconitase enzyme and what is it eventually going to do? It's going to inhibit this enzyme and this enzyme once it's inhibited it can't convert citrate into isocitrate so you can't you won't be able to generate a eventually NADHs, FADH2s, and ATP. And that is a very, very bad thing. So, fluoroacetate can actually cause inhibition of this aconitase enzyme. And again, it's within rat poison. So, if you, you know, somehow terribly take on too much rat poison for whatever reason, it can inhibit this enzyme. All right, cool. Now, we come on to this next one. So, we're going to convert isocitrate into alpha-ketoglutarate. All right, cool. How many carbons is this guy? Six carbons. How many is this guy? One, two, three, four, five. Okay, cool. Five carbons. That means I lost a carbon somewhere. Whenever you guys hear that, whenever you see a carbon missing, automatically assume that you lost that carbon in the form of CO2. What is that called? I know we talked about it. But what is it called whenever you lose a carbon in the form of CO2? What do they call that? They call it decarboxylation. Okay, so decarboxylation is the actual reaction in which you're removing the carbon. removing a carbon in the form of CO2, primarily a carboxyl carbon. Well, we're losing that. Now in this reaction we have a very, very important enzyme. This enzyme is called isocitrate D-. Hydrogenase. Right away, bells should start ringing in your head. Once you hear dehydrogenase, automatically know that you are going to be converting NAD positives into NADHs. Okay? Automatically. Once you guys see that automatically think, oh I'm going to make NADH's in this step. So what happens in this reaction? NAD positive is reacting in this step to generate NADH. That's what's happening in this step. I'm taking NAD positive and converting it into NADH. Cool. Now, you see how this step is? One direction. It's not bidirectional. So this is not a reversible enzyme. It can only be moving in one direction. Usually any enzyme that forms CO2 is generally usually irreversible. Isocitrate dehydrogenase has three pockets on it. Look, it's got this pocket, this pocket, this pocket. What is going to happen here? Okay. Again, realize that this is a Realize that whenever we're actually having high amounts of ATP, you guys can automatically think that. Whenever there's high amounts of ATP, this little Snoopy dog has three binding sites. Okay? Three binding sites. What's going to happen to this little Snoopy dog or the isocitrate dehydrogenase enzyme? If there's too much ATP, ATP will inhibit this enzyme. And that should already make sense because there's too much energy production. We want to slow it down. Whereas think about the opposite effect. If I'm breaking down a lot of ATP and generating a lot of ADP, that should stimulate this enzyme. And that it does, my friends. Okay. And for the last one, this one's kind of going to be like, what the heck? Where did that come from? Calcium is another strong stimulator of this enzyme. And this should actually make sense. Think about this in the muscles. In muscles, calcium is acting as a nice important type of signaling muscle. molecule to activate the cross-bridge formation within the skeletal muscles or even cardiac muscle, right? He's important for that because we need calcium in order for our muscles to contract. But another thing that we need for our muscles to contract is ATP. If this enzyme is stimulated, he's going to help to generate NADHs which will take those hydrides to the electron transport chain and generate ATP. So calcium is helping to stimulate this enzyme so we can make more ATP so we can have more contractions because he knows ATP is needed to detach. patch the myosin from the actin for the cross-bridge formation, right? So calcium is kind of letting this enzyme know, make more ATP. ADP, we're not, we don't have enough ATP in the cell. We need to make more. ATP is an inhibitor because it's saying we have too much, stop making more. Simple, nothing crazy about that. Okay, now we're going to move on to this next enzyme. This next enzyme is extremely important. We really need to remember this enzyme. This enzyme right here, look at this, she's got, you know, locks here. This is called alpha I'm going to do that key to glute rate kg The hydrogenase enzyme. This is an extremely, extremely crucial enzyme. Okay. Count how many carbons we have again. One, two, three, four, five for alpha-ketoglutarate. For succinyl-CoA, how many do I have? 1, 2, 3, 4. Okay, that means I must have lost the carbon. Oh, yeah, cool. So there must have been decarboxylation. I must have lost the carbon in the form of CO2. So there must have been another decarboxylation reaction. Oh, wait, Zach said whenever I have a dehydrogenase, automatically think NAD positive to NADH. Okay, so that's not bad. This reaction is complete. It's done. That's it. It's not that bad because all you got to remember is, okay, 5 to 4, loss of CO2, decarboxylation, NAD positive to NADH because there's a dehydrogenase enzyme. That's it. Now, we have to remember, look, this she's got three pockets. and her dreads. Okay? What's going to happen? Same thing. Now, think about this one. It's going to be a little tricky. Nothing crazy. You see Soxinokohe? He's just sitting here. He's going to tell you Tell this enzyme if there's too much of him and if this enzyme needs to stop. So look, look what succinyl-CoA can come over here and do. It can come and bind onto this enzyme. And it will inhibit this enzyme and tell this enzyme, don't keep converting alpha-ketoglutarate to succinyl-CoA. We don't need to do that anymore. There's either too much ATP, there's too much NADHs, there's too much energy produced in the cell. Stop. Okay. Now, the next one's a little weird, but it's not crazy. See these NADHs? If you start generating too much NADHs, that can also tell this enzyme to shut down. So this NADH can actually come over here, and what can it do? Look, here's our NADH. If there's too much NADHs, what will it do to this enzyme? It will inhibit this enzyme. Tell this enzyme, don't keep converting me alpha-ketoglutarate into succinyl-quade because there's already too much NADHs. We need to stop making as much. that will inhibit this enzyme. And the last thing is super simple because we already talked about him. Calcium right? Calcium is also going to work in this step too. So you're gonna have NADH who's going to be inhibiting this enzyme, succinyl-CoA which is going to be inhibiting this enzyme, and then what else is going to be working in this step? Calcium. Calcium is going to be doing what in this step? Calcium is going to be stimulating This enzyme here. Okay, so now that should make sense now, right? Because we generated CO2 by decarboxylation. We generated some NADHs out of this reaction because we had the alpha-ketoglutarate dehydrogenase. But then we need to be able to regulate this enzyme to control. how much activity is going on. If there's too much succinyl-CoA from too much Krebs cycle activity, it's going to inhibit this enzyme to stop this Krebs cycle from continuing to occur. If there's too much NADHs that are being generated, it'll also inhibit this enzyme, tell it not to continue to occur. Because we already have too much NADH and too much ATP. But then again, calcium, think of the muscles. Calcium is going to try to do what? Helps to be able to form that, you know, allow for the muscle contraction. But we need ATP in order for the muscles to contract. So without the ATP, the muscles won't be able to contract. So calcium is helping to activate this enzyme so we can speed up the ATP production. All right, cool. Now, why did I want to mention this enzyme and say it's extremely important? Okay. In your body, alpha-ketoglutarate is an integral component of an enzyme called histone demethylase. And this histone demethylase, basically what histone demethylases do, is let's say here's the DNA. Here's a sequence of DNA or something like that, right? And you know DNA is wrapped around histone proteins, and histone proteins are basically very important for being able to control the organ. of these DNA, the gene expression and stuff like that. So these histone proteins are actually going to be having the DNA wrapped around them. What histone demethylases do is you might have methyl groups on these guys here. which are basically controlling, you know, gene modification, epigenetics, and stuff like that, this histone demethylase will come over and remove those methyl groups. Alpha-ketoglutarate is a cofactor. It's a cofactor for this histone demethylase, right? In our body, we have that enzyme, right? So what was making the alpha-ketoglutarate, if you guys remember? We were taking what? We were having this alpha-ketoglutarate, which is going to be an important component of this step right here, right? Right. helping to synthesize you know being a component of the histone demethylase. If this alpha-ketoglutarate right so remember we had the isocitrate the isocitrate was actually being converted what isocitrate was being converted into alpha-ketoglutarate right and that was done by the isocitrate dehydrogenase enzyme. But then alpha-ketoglutarate is getting converted into what? It's getting converted into succinyl-CoA through what? Alpha-ketoglutarate dehydrogenase. In a condition in which there is a mutant form of that alpha-ketoglutarate dehydrogenase, specifically the one which is having NADPHs involved with it, not NADs, NADPHs. In a condition in which there is some type of mutation in this enzyme with the NADPHs, it can actually... convert instead of converting it into succinyl CoA and actually getting a lot of this alpha-ketoglutarate you can get another molecule here and it's called 2-hydroxyglutarate why am I telling you this because 2-hydroxyglutarate will come in and do what it'll bind and prevent this alpha-ketoglutarate from being able to bind if alpha-ketoglutarate can't bind onto the histone demethylases can you control the gene expression no if gene expression isn't controlled it can lead to tumors. It can lead to uncontrolled cell growth. Primarily super dangerous one, you've probably heard of it called gliomas. Gliomas are basically tumors that are occurring within the glial cells in the brain. One of the really really dangerous ones is the astrocytomas or the glioblastoma multiforme. So GBMs which are very very dangerous. You usually have an 80% metastatic rate and they're usually malignant and can cause you know unfortunate death. But again understanding how something so small that you would think you know there's metabolism. It can have such an amazing effect on your body. So again, any type of mutation, this alpha-ketoglutarate dehydrogenase, particularly with the NADPH1 instead of the NADH1, can lead to the formation of a byproduct called 2-hydroxyglutarate, which can inhibit the alpha-ketoglutarate from binding to the histone demethylase, inhibiting this enzyme, inhibiting gene expression, and leading to uncontrolled cell growth and tumor formation. Okay, now that we've got that out of the way, let's move on to the next one. Now we've got to take this succinic away. and I'm going to convert it into succinate. Okay. Well, what happened here? Okay. Somewhere in this reaction, oh, look at that. Alpha-Q to glutarate going to succinate. What did we miss? Well, over here we had that CoA. I should have a CoA on this guy. What does that mean? That means I added a CoA onto this step. Let's add that in there. So there must have been a Coenzyme A being added into this step. You know this alpha-Q to glutarate dehydrogenase? If you guys remember. the pyruvate dehydrogenase complex, this enzyme functions in the exact same mechanism. So if you guys remember that enzyme, you'll remember how this enzyme functions. Anyway, we add the CoA in, then look what happens. We get rid of the CoA. So then we lose the CoA in this step, but it's all for good reason. Just sometimes we might not like why it does this. Well what's happening here? Something really funky is happening. When we release the CoA, it generates a little bit of energy, a little bit of potential energy that our body uses to take GDP and an inorganic phosphate. and fuse that to form GTP. Okay, it's cool. But then you know who comes in? ADP. ADP's like, oh man, I'm going to pit pocket this guy so hard. So what does he do? ADP comes over here and steals the phosphate from the GTP. ADP, when he gains the phosphate, what does he turn into? He gains another phosphate, so he turns into ATP. Okay, that's cool. But what happens to the GTP? The GTP unfortunately goes back. back to GDP. Okay, so it's a cool way of our body being able to generate ATP through what's called substrate level phosphorylation. So again, what is that called? It's called substrate phosphorylation, which is completely different as compared to oxidative phosphorylation. So substrate phosphorylation doesn't generate as much ATP as compared to oxidative phosphorylation. Okay, so that's happening in this step. So we're developing ATP and that's coming because of releasing out the coenzyme A which creates a little bit of energy to take GDP and inorganic phosphate fuse them together to make GTP but then ADP comes over here pit pockets that phosphate from the GTP and makes ATP which converts the GTP back into GDP what enzyme is helping in this step Okay, this enzyme here converting succinyl-CoA into succinate, it's got a pretty cool enzyme. This is called, specifically, succinyl-CoA synthetase. Okay, so you have the succinyl-CoA synthetase enzyme, and what this enzyme is doing is, it's being involved in this step to stimulate the conversion of succinate will go into succinate. Now when we get that succinate, nothing crazy happens in this next step but let's see what's happening here nonetheless. Okay look we're taking succinate we're converting it into fumarate. When we take succinate and convert it into fumarate we have another enzyme. Look at this, look at this freak. Okay this enzyme right here is special. You don't know why, look where he's actually anchored. anchored on the mitochondrial membrane, specifically the inner mitochondrial membrane, the cristae. You know this is actually called complex II, enzyme complex II, it's a part of the electron transport chain, but we like to call it something else. We call it succinate dehydrogenase. Boom, light bulb. What does that mean? Automatically, you should think FAD in this case. to FADH2, but you guys are probably like, oh dude, what? You told me it was NAD. Any type of coenzyme, usually FAD or NAD, is usually involved whenever you hear dehydrogenase, okay? Now, because I'm forming FADH2, this is going to be helpful in energy production, but you know what else is also helpful for this? You know in certain conditions, it's called pheochromocytoma. So, called pheochromocytoma. There's some type of mutation in this enzyme. An alteration or mutation in this enzyme can cause a situation where you form a neuroblastoma. It's usually benign, meaning it's not metastatic, it doesn't spread. But this pheochromocytoma is usually a tumor that develops within the adrenal medulla. And it causes an excessive amount of epinephrine and norepinephrine to be produced, which causes an extreme hypertensive crisis. So a very, very dangerous condition. But just seeing any type of mutation in this enzyme can lead to this condition. pheochromocytoma. Alright, cool. So again, remember that this is enzyme complex too. It's a part of the electron transport chain and it's converting FAD to FADH2, but it's also reversible. So this reaction can be reversible. Alright, cool. So that's that step. Now we're going to take the fumarate and we're going to convert that into the malate. Okay. This enzyme is really, really simple. Nothing crazy about this enzyme. This enzyme is called fumarase. And look, we got Humpty Dumpty. He's sitting on this reaction. Humpty Dumpty is actually going to do what? He's going to throw some water into this reaction. He's like, ah, let me help out in this reaction to the best of my abilities. And he throws water into this reaction. But again, remember that this reaction is reversible. So what does he do in this reaction? Humpty Dumpty takes and throws water into this reaction to convert fumarate into malate. Now you might be like, okay, simple. It must not be that important of an enzyme. He is very important. You know, a condition which there is a deficiency in this enzyme, it can lead to the formation of what's called leomas or leomyomas too. And leomas are usually going to be tumors that develop within smooth muscle tissue. Usually they're benign. A perfect example of this one is they also call them fibroids, but it's some type of uterine. It's very, very common in the uterine smooth muscle and even in the kidneys. Okay? So this can happen in the uterine smooth muscle and it can happen in the kidneys. but usually there's some type of leoma and again just a deficiency in this enzyme can cause that significant change unbelievable okay so now we got malate malate has this Hades looking enzyme look at this look at this friend guy this guy right here is a cool enzyme I like him he's called malate Dehydrogenase. You guys should automatically think again. NAD positive to NADH. So what's happening here? I'm taking NAD positive and I'm converting it into NADH. Why? Because there is a dehydrogenase enzyme. present. When there's a dehydrogenase enzyme present, it's converting NAD positive to NADH in this step. This enzyme is also reversible, so this reverse reaction can occur, OAA to Mally, and we'll see that throughout more videos where we cover a little bit on gluconeogenesis. and even electron transport chain. Okay, now that we've done that, we've covered all of these different enzymes that are involved in these steps here. Now, one other thing I want to tell you guys is, is that when I'm taking this acetyl-CoA, what am I doing, right? I'm taking this acetyl-CoA, I'm combining with the oxaloacetate and having it react with citrate synthase to form citrate. Citrate is reacting with a connotase to make isocitrate. Isocitrate is going to be acted on by isocitrate dehydrogenase to make alpha-ketoglutarate. Okay. Alpha-ketoglutarate gets converted into succinyl-CoA when acted on by alpha-ketoglutarate dehydrogenase. The succinyl-CoA synthetase is going to be taking succinyl-CoA and converting it into succinate, which will generate a little bit of ATP in that step. And then succinate is converting it into fumarate. And then fumarate is being converted into malate and maloxyethanol. Back to OAA. How many acetyl-CoAs should I really be having going through this cycle? This is crucial. I have two pyruvates. Will two pyruvates get converted into two acetyl-CoAs? That means I make two turns. Well, if I make two turns, don't I really develop two FADH2s? Don't I really develop two NADHs? And don't I develop another two NADHs right here and another two NADHs right here and technically two ATP and two CoAs, right? And two CoAs being added. Okay, so how many CO2's did we generate out of this? We generated two in this step, and we generated two in this step. So two plus two is four. So we got four CO2's out of this. Okay. What about NADH's? I generated six NADH's. How did I generate six NADH's? Let's look. We generated two NADHs in this step going from malate to oxaloacetate, right? So that's two. I generated two NADHs in this step going from isocitrate to alpha-ketoglutarate. That's four. And I generated two more NADHs going from alpha-ketoglutarate to succinyl-CoA. That's six. Then what was the last thing that we generated? Two FADH2s. Okay, cool. So I got two FADH2s. Last thing. How many ATP did I generate? 2 ATP. And by what type of phosphorylation? Substrate phosphorylation. So again, I'm generating by substrate phosphorylation. And where is that happening? That's happening when I'm going from succinyl-CoA to succinate. Remember, I'm taking the GDP to GTP. having the ADP pick off that phosphate to form ATP, two of them, by substrate-level phosphorylation. So out of this, this is going to be the main products that you'll get out of this. And these NADHs and FADH2s will go and take these hydride ions to the electron transport chain where they'll be used to make ATP by oxidative phosphorylation. All right, engineers, so we went over a lot of information in this video. I hope it all made sense. I hope you guys did enjoy it. If you did, please hit the like button, subscribe, put a comment down in the comments section. All right, engineers, until next time.

That's where it came from. Okay, so now, when we go through the Krebs cycle, we've already gone over in great detail, we've already gone over the glycolysis pathway, we've actually... gone over all the glut transporters. We've gone over the glycolysis pathway of converting. What is this molecule right here?

This is glucose right here. We've converted glucose into pyruvate. And how many pyruvates have we actually made?

Technically we made two of these, right? Because we split the six carbon fragment into two three carbon fragments. So we've actually made two pyruvates.

And during that process, you guys already know that we generated two NADHs and two net ATP. And then, you know that we've already gone into detail whenever there's oxygen present, we can take this pyruvate, bring it into the mitochondria, and we can transition it, right? We can get ready to transition to the Krebs cycle.

And in that transition step, or that preparation step, what did we do? We added a coenzyme in. into this reaction right and then what else did we do we generated two NADHs and we produced two CO2s by decarboxylation and that was done through this whole pyruvate dehydrogenase complex with the E1 E2 and E3 we already gone up we already went over that in great detail and all the mechanisms. Now we're going into this next thing, which is the Krebs cycle. So we formed acetyl-CoA from the transition step, right?

This molecule right here is our acetyl-CoA. Now what we're going to do is we're going to convert this acetyl-CoA, we're going to fuse it with this four carbon fragment right here. This four carbon fragment is actually referred to as oxaloacetate. So again, this guy right here is called, I'm going to denote it.

I'm going to abbreviate it OAA. Oxaloacetate is going to combine with the acetyl-CoA. When these two substrates combine, they fuse together in the presence of this enzyme.

talk about this enzyme in a second. But OAA is a four carbon structure combining with a two carbon structure. And again, what is this red structure coming off of the acetyl-CoA? That's the coenzyme A.

When this acetyl-CoA and when this OAA combine with this enzyme, they form a six carbon molecule. Look, one, two, three, four, five, six. What is this molecule called? This is called citrate.

You know what's really interesting? Unisitrate is Krebs'starting substrate for making oxaloacetate. What did I just do? I gave you guys a little quick mnemonic to be able to remember all of this. So it's an easier one to be able to do.

Okay, so how do I remember? Again, oxaloacetate and acetyl-CoA come together in the presence of this enzyme to form citrate. And I like to remember this.

Citrate is Krebs'starting substrate for making oxaloacetate. What is is for? Is is for isocitrate.

So let's get all these intermediates out of the way. Just an easy way to be able to remember them because that's what we long for. All right? Sometimes you can just get it out of the way, the memorization, right? Krebs is for alpha-ketoglutarate.

I might refer to it as AKG whenever you guys see it like that. Starting is for succinyl-CoA. Succinyl. CoA. Substrate is for succinate.

This is succinate. 4 is fumarate. And then the last one is making which is going to be malate and the last one is oxaloacetate.

So again it goes citrate is Krebs starting substrate for making oxaloacetate. Just a little quick mnemonic. would help out to just memorize you know the basic intermediates now that we've done that really there's nothing crazy else that we have to know other than just the regulatory steps and what's happening in between okay cool so let's do that now that we know the intermediates let's focus on the enzymes and and what's produced and what's happening in each step.

So acetyl-CoA and OAA, or oxaloacetate. When these two are fusing, there's a special enzyme. And what is this enzyme doing?

It's forming citrate, it's synthesizing citrate. So what would that enzyme be called? You call it citrate. Synthase. So there's a citrate synthase enzyme.

This citrate synthase, what is he doing? He's taking the oxaloacetate in one part, taking the acetylcholine in the other part, fusing them together and making citrate. Now the question is, this enzyme is extremely very highly regular. So it's going to control this step.

So acetyl-CoA going into citrate with oxaloacetate, this is not a reversible step. This is a one-way reaction. So what does citrate synthase have to be regulated by?

Okay, it's going to go on and on what you guys are going to see throughout a series these biochem videos. Think about this. If our body is having a lot of metabolism, so it's occurring a lot, a lot of metabolism, a lot of Krebs cycle, a lot of electron transport chain activity, I'm making a lot of ATP.

If I'm making a lot of ATP, do you think I'm going to want to keep having the Krebs cycle going on, making more NADHs and FADH2s? No, because I already have too much of it. This is going to inhibit it. It's going to allosterically inhibit this enzyme.

Same thing. In the Krebs cycle, you'll see... that will generate a lot of what's called NADHs that you see here. NADHs, if there's too many of them, it's also basically telling this enzyme, there's a lot of energy supply within the cell.

We don't need any more. Shut down. Don't do this anymore.

Okay, then we have another one, citrate himself. You know whenever there's actually too much citrate, citrate can actually come back and inhibit this enzyme. So citrate himself. can come back and inhibit this enzyme. So a citrate can say, okay, there's way too much of me.

Because generally, what's going to happen when you make citrate? It'll automatically get converted into isocitrate, generally. Some of this citrate can also get converted into the basic units for fatty acids called malonyl-CoA. that but generally it should be progressing somewhere it shouldn't be building up when it's building up it's letting the citrate synthase know don't make any more of me stop working and then there's another one he's all the way down there though it's called called succinyl CoA. So succinyl CoA is also an allosteric inhibitor.

He's just a little bit more downstream and he's just telling this enzyme, hey, before you even think about making citrate, there's already too much of me. So shut down and stop making more citrate and making more of me, making more NADHs, more ATP, just stop doing that. And these are generally the main allosteric regulators of this citrate synthase.

Now what would be a stimulator? We've already talked about this so many times, but it's... It's a good way to keep continuously reviewing. ATP gets broken down into what, guys?

It gets broken down into ADP and inorganic phosphate. If you're breaking down a lot of ATP, you're going to build up a lot of ADP. And this is going to signify that you are actually not having a lot of ATP within the cell.

If there's not a lot of ATP in the cell, that's not good because ATP is needed for transport mechanisms, for metabolic pathways, for DNA synthesis, so many different things, ion channels. So ADP... would be a very powerful allosteric stimulator of this enzyme. It would let this enzyme know, hey, there's not a lot of ATP.

You need to continue to keep going through the Krebs cycle, making more NADHs and FADH2s and make more ATP. So that would be that guy. So generally, this is how we're going to allosterically regulate this googly-eyed enzyme. Okay, because this googly-eyed enzyme is involved in this step right here, converting the acetyl-CoA into citrate. Very, very highly regulated step.

Okay, so we're done with that one. Okay, so now we got this Betty White enzyme. Okay, this Betty White enzyme with the perm going on is converting citrate, which is a six carbon molecule into what? Okay, one, two, three, four, five, six.

It's still six carbons. So what's really happening? It's just an isomerization reaction.

And isomerization reactions, all you're doing is you're just shuffling around the hydrogens and the carbons, but there should still be the same number of carbons and hydrogens and oxygens in this guy as there is carbons, hydrogens, and carbons. and oxygens in this guy. So it's just shuffling things around. Not a crazy crucial step, but the enzyme controlling this step, as you guys can see, is doing what? It's able to move in the reverse direction.

So whenever there is too much isocitrate, you can convert it back into citrate. It is possible. And it actually does happen, and you'll see this whenever we talk about this in fatty acid synthesis. But the enzyme that's controlling this is called aconitase. A-C-O-N-I-T-A-S-E.

Okay, aconitase enzyme. So there's, you know, just because it's not controlling and it's not highly regulated and is reversible doesn't mean that this enzyme isn't important. You know there's a rat poison?

Within rat poison there's a chemical that's present called fluoroacetate. And what happened? What happens with this fluoroacetate is it's kind of acting like acetyl-CoA.

You know, acetate is just basically another fancy word for saying it's a two-carbon structure. All it has is just a fluorine attached to it. So it's going to get actually converted.

It's going to act like fluoroacetate. So you know how you're going to have acetyl-CoA here? You're going to have this fluorine.

acetyl-CoA which gets converted into fluorocitrate and that fluorocitrate binds on to the aconitase enzyme and what is it eventually going to do? It's going to inhibit this enzyme and this enzyme once it's inhibited it can't convert citrate into isocitrate so you can't you won't be able to generate a eventually NADHs, FADH2s, and ATP. And that is a very, very bad thing.

So, fluoroacetate can actually cause inhibition of this aconitase enzyme. And again, it's within rat poison. So, if you, you know, somehow terribly take on too much rat poison for whatever reason, it can inhibit this enzyme.

All right, cool. Now, we come on to this next one. So, we're going to convert isocitrate into alpha-ketoglutarate.

All right, cool. How many carbons is this guy? Six carbons.

How many is this guy? One, two, three, four, five. Okay, cool.

Five carbons. That means I lost a carbon somewhere. Whenever you guys hear that, whenever you see a carbon missing, automatically assume that you lost that carbon in the form of CO2.

What is that called? I know we talked about it. But what is it called whenever you lose a carbon in the form of CO2? What do they call that?

They call it decarboxylation. Okay, so decarboxylation is the actual reaction in which you're removing the carbon. removing a carbon in the form of CO2, primarily a carboxyl carbon.

Well, we're losing that. Now in this reaction we have a very, very important enzyme. This enzyme is called isocitrate D-. Hydrogenase. Right away, bells should start ringing in your head.

Once you hear dehydrogenase, automatically know that you are going to be converting NAD positives into NADHs. Okay? Automatically.

Once you guys see that automatically think, oh I'm going to make NADH's in this step. So what happens in this reaction? NAD positive is reacting in this step to generate NADH. That's what's happening in this step. I'm taking NAD positive and converting it into NADH.

Cool. Now, you see how this step is? One direction.

It's not bidirectional. So this is not a reversible enzyme. It can only be moving in one direction.

Usually any enzyme that forms CO2 is generally usually irreversible. Isocitrate dehydrogenase has three pockets on it. Look, it's got this pocket, this pocket, this pocket.

What is going to happen here? Okay. Again, realize that this is a Realize that whenever we're actually having high amounts of ATP, you guys can automatically think that. Whenever there's high amounts of ATP, this little Snoopy dog has three binding sites. Okay?

Three binding sites. What's going to happen to this little Snoopy dog or the isocitrate dehydrogenase enzyme? If there's too much ATP, ATP will inhibit this enzyme.

And that should already make sense because there's too much energy production. We want to slow it down. Whereas think about the opposite effect. If I'm breaking down a lot of ATP and generating a lot of ADP, that should stimulate this enzyme. And that it does, my friends.

Okay. And for the last one, this one's kind of going to be like, what the heck? Where did that come from?

Calcium is another strong stimulator of this enzyme. And this should actually make sense. Think about this in the muscles.

In muscles, calcium is acting as a nice important type of signaling muscle. molecule to activate the cross-bridge formation within the skeletal muscles or even cardiac muscle, right? He's important for that because we need calcium in order for our muscles to contract.

But another thing that we need for our muscles to contract is ATP. If this enzyme is stimulated, he's going to help to generate NADHs which will take those hydrides to the electron transport chain and generate ATP. So calcium is helping to stimulate this enzyme so we can make more ATP so we can have more contractions because he knows ATP is needed to detach.

patch the myosin from the actin for the cross-bridge formation, right? So calcium is kind of letting this enzyme know, make more ATP. ADP, we're not, we don't have enough ATP in the cell.

We need to make more. ATP is an inhibitor because it's saying we have too much, stop making more. Simple, nothing crazy about that.

Okay, now we're going to move on to this next enzyme. This next enzyme is extremely important. We really need to remember this enzyme. This enzyme right here, look at this, she's got, you know, locks here. This is called alpha I'm going to do that key to glute rate kg The hydrogenase enzyme.

This is an extremely, extremely crucial enzyme. Okay. Count how many carbons we have again. One, two, three, four, five for alpha-ketoglutarate. For succinyl-CoA, how many do I have?

1, 2, 3, 4. Okay, that means I must have lost the carbon. Oh, yeah, cool. So there must have been decarboxylation.

I must have lost the carbon in the form of CO2. So there must have been another decarboxylation reaction. Oh, wait, Zach said whenever I have a dehydrogenase, automatically think NAD positive to NADH.

Okay, so that's not bad. This reaction is complete. It's done.

That's it. It's not that bad because all you got to remember is, okay, 5 to 4, loss of CO2, decarboxylation, NAD positive to NADH because there's a dehydrogenase enzyme. That's it.

Now, we have to remember, look, this she's got three pockets. and her dreads. Okay? What's going to happen? Same thing.

Now, think about this one. It's going to be a little tricky. Nothing crazy.

You see Soxinokohe? He's just sitting here. He's going to tell you Tell this enzyme if there's too much of him and if this enzyme needs to stop. So look, look what succinyl-CoA can come over here and do. It can come and bind onto this enzyme.

And it will inhibit this enzyme and tell this enzyme, don't keep converting alpha-ketoglutarate to succinyl-CoA. We don't need to do that anymore. There's either too much ATP, there's too much NADHs, there's too much energy produced in the cell. Stop. Okay.

Now, the next one's a little weird, but it's not crazy. See these NADHs? If you start generating too much NADHs, that can also tell this enzyme to shut down. So this NADH can actually come over here, and what can it do? Look, here's our NADH.

If there's too much NADHs, what will it do to this enzyme? It will inhibit this enzyme. Tell this enzyme, don't keep converting me alpha-ketoglutarate into succinyl-quade because there's already too much NADHs. We need to stop making as much.

that will inhibit this enzyme. And the last thing is super simple because we already talked about him. Calcium right?

Calcium is also going to work in this step too. So you're gonna have NADH who's going to be inhibiting this enzyme, succinyl-CoA which is going to be inhibiting this enzyme, and then what else is going to be working in this step? Calcium. Calcium is going to be doing what in this step?

Calcium is going to be stimulating This enzyme here. Okay, so now that should make sense now, right? Because we generated CO2 by decarboxylation. We generated some NADHs out of this reaction because we had the alpha-ketoglutarate dehydrogenase. But then we need to be able to regulate this enzyme to control.

how much activity is going on. If there's too much succinyl-CoA from too much Krebs cycle activity, it's going to inhibit this enzyme to stop this Krebs cycle from continuing to occur. If there's too much NADHs that are being generated, it'll also inhibit this enzyme, tell it not to continue to occur.

Because we already have too much NADH and too much ATP. But then again, calcium, think of the muscles. Calcium is going to try to do what?

Helps to be able to form that, you know, allow for the muscle contraction. But we need ATP in order for the muscles to contract. So without the ATP, the muscles won't be able to contract.

So calcium is helping to activate this enzyme so we can speed up the ATP production. All right, cool. Now, why did I want to mention this enzyme and say it's extremely important? Okay.

In your body, alpha-ketoglutarate is an integral component of an enzyme called histone demethylase. And this histone demethylase, basically what histone demethylases do, is let's say here's the DNA. Here's a sequence of DNA or something like that, right? And you know DNA is wrapped around histone proteins, and histone proteins are basically very important for being able to control the organ.

of these DNA, the gene expression and stuff like that. So these histone proteins are actually going to be having the DNA wrapped around them. What histone demethylases do is you might have methyl groups on these guys here.

which are basically controlling, you know, gene modification, epigenetics, and stuff like that, this histone demethylase will come over and remove those methyl groups. Alpha-ketoglutarate is a cofactor. It's a cofactor for this histone demethylase, right?

In our body, we have that enzyme, right? So what was making the alpha-ketoglutarate, if you guys remember? We were taking what?

We were having this alpha-ketoglutarate, which is going to be an important component of this step right here, right? Right. helping to synthesize you know being a component of the histone demethylase.

If this alpha-ketoglutarate right so remember we had the isocitrate the isocitrate was actually being converted what isocitrate was being converted into alpha-ketoglutarate right and that was done by the isocitrate dehydrogenase enzyme. But then alpha-ketoglutarate is getting converted into what? It's getting converted into succinyl-CoA through what? Alpha-ketoglutarate dehydrogenase. In a condition in which there is a mutant form of that alpha-ketoglutarate dehydrogenase, specifically the one which is having NADPHs involved with it, not NADs, NADPHs.

In a condition in which there is some type of mutation in this enzyme with the NADPHs, it can actually... convert instead of converting it into succinyl CoA and actually getting a lot of this alpha-ketoglutarate you can get another molecule here and it's called 2-hydroxyglutarate why am I telling you this because 2-hydroxyglutarate will come in and do what it'll bind and prevent this alpha-ketoglutarate from being able to bind if alpha-ketoglutarate can't bind onto the histone demethylases can you control the gene expression no if gene expression isn't controlled it can lead to tumors. It can lead to uncontrolled cell growth. Primarily super dangerous one, you've probably heard of it called gliomas. Gliomas are basically tumors that are occurring within the glial cells in the brain.

One of the really really dangerous ones is the astrocytomas or the glioblastoma multiforme. So GBMs which are very very dangerous. You usually have an 80% metastatic rate and they're usually malignant and can cause you know unfortunate death.

But again understanding how something so small that you would think you know there's metabolism. It can have such an amazing effect on your body. So again, any type of mutation, this alpha-ketoglutarate dehydrogenase, particularly with the NADPH1 instead of the NADH1, can lead to the formation of a byproduct called 2-hydroxyglutarate, which can inhibit the alpha-ketoglutarate from binding to the histone demethylase, inhibiting this enzyme, inhibiting gene expression, and leading to uncontrolled cell growth and tumor formation.

Okay, now that we've got that out of the way, let's move on to the next one. Now we've got to take this succinic away. and I'm going to convert it into succinate.

Okay. Well, what happened here? Okay.

Somewhere in this reaction, oh, look at that. Alpha-Q to glutarate going to succinate. What did we miss?

Well, over here we had that CoA. I should have a CoA on this guy. What does that mean?

That means I added a CoA onto this step. Let's add that in there. So there must have been a Coenzyme A being added into this step. You know this alpha-Q to glutarate dehydrogenase? If you guys remember.

the pyruvate dehydrogenase complex, this enzyme functions in the exact same mechanism. So if you guys remember that enzyme, you'll remember how this enzyme functions. Anyway, we add the CoA in, then look what happens. We get rid of the CoA.

So then we lose the CoA in this step, but it's all for good reason. Just sometimes we might not like why it does this. Well what's happening here?

Something really funky is happening. When we release the CoA, it generates a little bit of energy, a little bit of potential energy that our body uses to take GDP and an inorganic phosphate. and fuse that to form GTP.

Okay, it's cool. But then you know who comes in? ADP.

ADP's like, oh man, I'm going to pit pocket this guy so hard. So what does he do? ADP comes over here and steals the phosphate from the GTP. ADP, when he gains the phosphate, what does he turn into?

He gains another phosphate, so he turns into ATP. Okay, that's cool. But what happens to the GTP? The GTP unfortunately goes back. back to GDP.

Okay, so it's a cool way of our body being able to generate ATP through what's called substrate level phosphorylation. So again, what is that called? It's called substrate phosphorylation, which is completely different as compared to oxidative phosphorylation. So substrate phosphorylation doesn't generate as much ATP as compared to oxidative phosphorylation. Okay, so that's happening in this step.

So we're developing ATP and that's coming because of releasing out the coenzyme A which creates a little bit of energy to take GDP and inorganic phosphate fuse them together to make GTP but then ADP comes over here pit pockets that phosphate from the GTP and makes ATP which converts the GTP back into GDP what enzyme is helping in this step Okay, this enzyme here converting succinyl-CoA into succinate, it's got a pretty cool enzyme. This is called, specifically, succinyl-CoA synthetase. Okay, so you have the succinyl-CoA synthetase enzyme, and what this enzyme is doing is, it's being involved in this step to stimulate the conversion of succinate will go into succinate.

Now when we get that succinate, nothing crazy happens in this next step but let's see what's happening here nonetheless. Okay look we're taking succinate we're converting it into fumarate. When we take succinate and convert it into fumarate we have another enzyme. Look at this, look at this freak. Okay this enzyme right here is special.

You don't know why, look where he's actually anchored. anchored on the mitochondrial membrane, specifically the inner mitochondrial membrane, the cristae. You know this is actually called complex II, enzyme complex II, it's a part of the electron transport chain, but we like to call it something else.

We call it succinate dehydrogenase. Boom, light bulb. What does that mean? Automatically, you should think FAD in this case. to FADH2, but you guys are probably like, oh dude, what?

You told me it was NAD. Any type of coenzyme, usually FAD or NAD, is usually involved whenever you hear dehydrogenase, okay? Now, because I'm forming FADH2, this is going to be helpful in energy production, but you know what else is also helpful for this? You know in certain conditions, it's called pheochromocytoma. So, called pheochromocytoma.

There's some type of mutation in this enzyme. An alteration or mutation in this enzyme can cause a situation where you form a neuroblastoma. It's usually benign, meaning it's not metastatic, it doesn't spread. But this pheochromocytoma is usually a tumor that develops within the adrenal medulla. And it causes an excessive amount of epinephrine and norepinephrine to be produced, which causes an extreme hypertensive crisis.

So a very, very dangerous condition. But just seeing any type of mutation in this enzyme can lead to this condition. pheochromocytoma. Alright, cool.

So again, remember that this is enzyme complex too. It's a part of the electron transport chain and it's converting FAD to FADH2, but it's also reversible. So this reaction can be reversible.

Alright, cool. So that's that step. Now we're going to take the fumarate and we're going to convert that into the malate.

Okay. This enzyme is really, really simple. Nothing crazy about this enzyme. This enzyme is called fumarase.

And look, we got Humpty Dumpty. He's sitting on this reaction. Humpty Dumpty is actually going to do what?

He's going to throw some water into this reaction. He's like, ah, let me help out in this reaction to the best of my abilities. And he throws water into this reaction.

But again, remember that this reaction is reversible. So what does he do in this reaction? Humpty Dumpty takes and throws water into this reaction to convert fumarate into malate.

Now you might be like, okay, simple. It must not be that important of an enzyme. He is very important.

You know, a condition which there is a deficiency in this enzyme, it can lead to the formation of what's called leomas or leomyomas too. And leomas are usually going to be tumors that develop within smooth muscle tissue. Usually they're benign.

A perfect example of this one is they also call them fibroids, but it's some type of uterine. It's very, very common in the uterine smooth muscle and even in the kidneys. Okay?

So this can happen in the uterine smooth muscle and it can happen in the kidneys. but usually there's some type of leoma and again just a deficiency in this enzyme can cause that significant change unbelievable okay so now we got malate malate has this Hades looking enzyme look at this look at this friend guy this guy right here is a cool enzyme I like him he's called malate Dehydrogenase. You guys should automatically think again.

NAD positive to NADH. So what's happening here? I'm taking NAD positive and I'm converting it into NADH.

Why? Because there is a dehydrogenase enzyme. present. When there's a dehydrogenase enzyme present, it's converting NAD positive to NADH in this step. This enzyme is also reversible, so this reverse reaction can occur, OAA to Mally, and we'll see that throughout more videos where we cover a little bit on gluconeogenesis.

and even electron transport chain. Okay, now that we've done that, we've covered all of these different enzymes that are involved in these steps here. Now, one other thing I want to tell you guys is, is that when I'm taking this acetyl-CoA, what am I doing, right? I'm taking this acetyl-CoA, I'm combining with the oxaloacetate and having it react with citrate synthase to form citrate. Citrate is reacting with a connotase to make isocitrate.

Isocitrate is going to be acted on by isocitrate dehydrogenase to make alpha-ketoglutarate. Okay. Alpha-ketoglutarate gets converted into succinyl-CoA when acted on by alpha-ketoglutarate dehydrogenase.

The succinyl-CoA synthetase is going to be taking succinyl-CoA and converting it into succinate, which will generate a little bit of ATP in that step. And then succinate is converting it into fumarate. And then fumarate is being converted into malate and maloxyethanol.

Back to OAA. How many acetyl-CoAs should I really be having going through this cycle? This is crucial.

I have two pyruvates. Will two pyruvates get converted into two acetyl-CoAs? That means I make two turns.

Well, if I make two turns, don't I really develop two FADH2s? Don't I really develop two NADHs? And don't I develop another two NADHs right here and another two NADHs right here and technically two ATP and two CoAs, right?

And two CoAs being added. Okay, so how many CO2's did we generate out of this? We generated two in this step, and we generated two in this step. So two plus two is four.

So we got four CO2's out of this. Okay. What about NADH's?

I generated six NADH's. How did I generate six NADH's? Let's look. We generated two NADHs in this step going from malate to oxaloacetate, right?

So that's two. I generated two NADHs in this step going from isocitrate to alpha-ketoglutarate. That's four.

And I generated two more NADHs going from alpha-ketoglutarate to succinyl-CoA. That's six. Then what was the last thing that we generated?

Two FADH2s. Okay, cool. So I got two FADH2s.

Last thing. How many ATP did I generate? 2 ATP. And by what type of phosphorylation?

Substrate phosphorylation. So again, I'm generating by substrate phosphorylation. And where is that happening?

That's happening when I'm going from succinyl-CoA to succinate. Remember, I'm taking the GDP to GTP. having the ADP pick off that phosphate to form ATP, two of them, by substrate-level phosphorylation.

So out of this, this is going to be the main products that you'll get out of this. And these NADHs and FADH2s will go and take these hydride ions to the electron transport chain where they'll be used to make ATP by oxidative phosphorylation. All right, engineers, so we went over a lot of information in this video. I hope it all made sense. I hope you guys did enjoy it.

If you did, please hit the like button, subscribe, put a comment down in the comments section. All right, engineers, until next time.

Transcript for:Understanding the Krebs Cycle Process

Transcript for:
Understanding the Krebs Cycle Process