Citric Acid Cycle 1: Study with Video Lessons, Practice Problems & Examples

The citric acid cycle begins with acetyl CoA combining with oxaloacetate to form citrate, generating 3 NADH, 1 FADH₂, and 1 GTP or ATP per cycle. Key reactions include the decarboxylation steps that release carbon dioxide and produce NADH. Notably, succinate is symmetric, leading to random orientation in enzyme interactions. The cycle's driving reactions (steps 1, 3, and 4) have negative delta G values, ensuring a consistent metabolic flow. Ultimately, the cycle regenerates oxaloacetate, ready for another turn, emphasizing its role in energy production and metabolic pathways.

Citric Acid Cycle 1

Before looking at each individual step of the citric acid cycle, I want to take a look at the process as a whole. You know, study the forest before studying the trees. So if you input one acetyl CoA into the citric acid cycle, you are going to get 3 NADH, 1 FADH₂, and 1 GTP or ATP and we'll talk more about why it's a GTP or ATP later. All you really need to know is that you're generating 1 nucleotide triphosphate. Now, remember that glycolysis is going to actually yield 2 acetyl CoA at this point in the metabolic pathway. So if you are trying to trace all of this with glucose as your origin, you're going to need to double your numbers here. It's also worth noting that this is also going to give off 2 carbon dioxides but that's really the end of their story. Whereas these molecules, that's the money, right? That's what's going to get you your ATP payoff. So taking a look at this figure, you'll notice that none of chemical structures are shown. That is intentional. Don't worry about those. You'll get to see them in the following pages when we look at each reaction individually. For now I just want to guide you through this diagram and show you really what its main purpose is which is tracking carbons and looking at the, the overall like important things that are happening during the citric acid cycle. So again, start with Acetyl CoA which you might recall is made of either carbon 1 or 6 and 2 or 5 from glucose and it is combined with this molecule oxaloacetate, 4 carbon molecule and they're going to make citrate. And notice that the, acetyl CoA carbons are black so you can follow them through the cycle. And, the carbons from oxaloacetate are white and gray. And those white ones are going to be the ones that come off as carbon dioxide momentarily. And just to be crystal clear, this is carbon 2 or 5 from Acetyl CoA and this is carbon 1 or 6. I'm sorry. From glucose. From glucose. Obviously acetyl CoA's carbon numbering is different than that of glucose. So, in the following reaction, we form isocitrate. Not super important. What's going on here? You remove a water and then you add it back in. Biochemists biochemists sometimes call that the ferris wheel or this they call this enzyme the ferris wheel because of what it does. You know, they have a particular brand of humor, let's say. Let me actually just jump out of the image here so you can see where we're at. I'm not blocking it. So this next reaction, this is one of the important ones. Right? Isocitrate to alpha keto Glutarate. This is where we lose our first carbon dioxide. It's this one coming off and we also are gonna generate an NADH in this reaction which is going to go on to the electron transport chain. Chain. You know we'll get to that story in the next exam review. And this next reaction is also one of the one of the, you know, really big important ones where Alpha Ketoglutarate goes to Succinal CoA and it's where this carbon comes off as carbon dioxide and we form another NADH and and you might also notice that coenzyme a is going to come back into the picture. Now in the following reaction where Succinyl CoA form is made into whoops. Innate. This is where we're going to produce our GTP. So GDP and inorganic phosphate, substrate level phosphorylation make GTP. In some cells. This will actually be used to make, an ATP by substrate level phosphorylation with ADP and inorganic phosphate. Not every cell is going to do this. Some will keep this as GTP. That's why it's an or situation, right? GTP or ATP, it doesn't really matter for us though because in biochemical terms, these are just nucleotide triphosphates. They're worth the same amount of energy. Let's put it that way. In terms of currency, these are both, you know, dollar bills or whatever. The same value. Anyways, what is important about this part of the figure that I do want to point out is we have a change in color scheme. Notice that the colors here are different from the colors here and there's a very important reason for that and that is that succinate is a symmetric molecule. So it's almost like it has a mirror running through its center, right? It's or each half is like a mirror of the other half. Now because of this, this carbon right here, this this carbon right here can wind up in this position or this position. So, that's why I'm changing the coloring scheme from here on out, all right? What I don't want you to confuse, don't think that these 2 gray carbons are now these 2 gray carbons. That is wrong. No. That is not what's happening here. What's happening is I'm representing, the color coding of this molecule in terms of, what's going to be, coming off in the in the following cycle. And the reason I'm changing the colors like this is again because, succinate is symmetric so its orientation in the active site of, the enzyme that carries out. This reaction is randomized meaning, you know, it it basically doesn't matter or it's it's not that it doesn't matter, it's like, it's random whether this again, you know, this carbon here winds up either up here or down here. So just to be crystal clear, that means that this carbon can wind up up here or down here as well. You know, they're going to be opposites, so they can either kind of like go over like this or like that. And again, it's random. We don't know so I'm changing the color scheme. Sorry to harp on that. I just want to make sure that it's crystal clear what's going on here and I don't want anyone to get confused and think that these gray ones are the same on both sides. Okay. Moving on. Succinate will be turned into fumarate and we are going to generate our, one and only FADH₂. We only produce 1 in citric acid or per turn of the citric acid cycle, it's right here and from here, fumarate will be converted into malate and then malate will be reduced, into oxaloacetate. Oh and just to be again sorry, just to be super, super clear, it's only succinate that is, symmetric and can have that random orientation in the enzyme's active site just because these, you know, look the same as succinate, you know, in terms of color scheme, don't think that their orientation is randomized too. So anyway, we end by regenerating oxaloacetate, produce our final NADH, and we are ready for another acetyl CoA to enter our cycle. Now, really important thing I want to point out while we're still looking at this image. Let's go ahead and number all the steps, right? So here's 1, 2, 3, 4, 5, 6, 7, and 8. Okay. Steps 1, 3, and 4 are the major drivers of this process because they have a negative delta g. These reactions here, 8, 7, 6, and 5, these can be reversed actually pretty easily and we're going to talk about that, at the end this, exam review. We're gonna talk a little bit more about that. But these reactions are readily reversible, as is reaction number 2. And the reason for that is because their delta Gs are close to 0. So, reactions 1, 3, and 4 are the reason this process is driven this way, consistently. They are the drivers of this cycle. And again last note, about labeled about labeled carbons. Basically what I'm saying is if we put in our labeled carbons here, right? Let's say that our black carbons are are labeled. That's what the black carbons mean, right? Let's, you know, just pretend for a moment that, those are labeled like with, you know, carbon 14 or something like that. And they go through the cycle. What I mean by, the note that only half the labeled carbons come off due to the randomization of succinate's orientation is, you know, basically what we were talking about down here. This in terms of, this oxaloacetate after our radiolabeled carbons go in, either one of these could be our carbon 14, right? We're either gonna have our carbon14 and we won't know which. We won't know which is which. But either way, only these white carbons are going to be the ones that come off in the following cycle. So, you know, depending on which orientation we have, this one or this one or rather regardless of which orientation we have, only one of those carbon 14s will come off in the next turn of the cycle. Meaning 다 that if we put in one batch of, radio labeled carbons, for example like 1 mole, only half will come off the first time. And the next time, only a quarter will come off. Next time, only an eighth will come off. Don't worry, we're going to revisit this concept again in case you're not totally 100% clear on it right now. But the point is just where is all of this stuff positioned in terms of what's happening at that reaction with succinate. Alright. Now,

Here’s what students ask on this topic:

What are the main products of the citric acid cycle?

The main products of the citric acid cycle per turn are 3 NADH, 1 FADH₂, and 1 GTP or ATP. Additionally, 2 molecules of CO₂ are released. These products are crucial for cellular respiration, as NADH and FADH₂ carry electrons to the electron transport chain, where they help generate ATP. The GTP or ATP produced can be used directly by the cell for energy. Remember, since glycolysis produces 2 acetyl CoA molecules from one glucose molecule, the cycle runs twice per glucose, doubling these numbers.

Why is succinate considered symmetric in the citric acid cycle?

Succinate is considered symmetric because it has a mirror plane running through its center, meaning each half of the molecule is a mirror image of the other. This symmetry leads to random orientation in the enzyme's active site during the citric acid cycle. As a result, the specific carbon atoms from succinate can end up in different positions in subsequent reactions, making it difficult to track individual carbon atoms through the cycle.

Which steps in the citric acid cycle have a negative delta G and drive the process?

Steps 1, 3, and 4 in the citric acid cycle have a negative delta G, making them the major drivers of the process. These steps are:

• Step 1: Acetyl CoA combines with oxaloacetate to form citrate.
• Step 3: Isocitrate is converted to α-ketoglutarate, releasing CO₂ and producing NADH.
• Step 4: α-Ketoglutarate is converted to succinyl CoA, releasing another CO₂ and producing NADH.

These reactions are energetically favorable and ensure the cycle proceeds in a consistent direction.

How does the citric acid cycle regenerate oxaloacetate?

The citric acid cycle regenerates oxaloacetate through a series of reactions starting from succinate. Succinate is converted to fumarate, which is then converted to malate. Finally, malate is oxidized to regenerate oxaloacetate. This regeneration is crucial because oxaloacetate is needed to combine with acetyl CoA to start another turn of the cycle, ensuring continuous energy production.

What is the significance of NADH and FADH₂ produced in the citric acid cycle?

NADH and FADH₂ produced in the citric acid cycle are essential for cellular respiration. They carry high-energy electrons to the electron transport chain in the mitochondria. Here, the electrons are used to create a proton gradient across the mitochondrial membrane, which drives the synthesis of ATP through oxidative phosphorylation. This process is the primary way cells generate ATP, the energy currency of the cell.