Krebs Cycle: Carbon Oxidation and ATP Generation

The Krebs cycle, or citric acid cycle, oxidizes pyruvate into acetyl CoA, generating NADH, FADH2, CO2, and ATP.

### Cellular Respiration: Preparatory Steps and the Krebs Cycle
* 🔋 After glycolysis, the two molecules of pyruvate produced are each converted to acetyl CoA in the preparatory step, releasing **two molecules of CO2** and generating **two NADH molecules**.
* 🔄 The Krebs cycle, also known as the citric acid cycle, occurs in the mitochondria and **requires oxygen**. It begins with the combination of acetyl CoA (2 carbons) with oxaloacetate (4 carbons) to form **citrate (6 carbons)**.
* 📊 For each turn of the Krebs cycle, there is a **net production of 3 NADH, 1 FADH2, 1 ATP (or GTP), and 2 CO2**. Since there are **two acetyl CoA molecules per glucose molecule**, these numbers are **doubled**.
* 🔴 "At this point, all of the carbons of glucose have been completely oxidized into CO2 because the **first two were oxidized at the prep step**."
* 🔵 The total ATP production from glycolysis and the Krebs cycle at this stage is **4 ATP (2 from glycolysis, 2 from the Krebs cycle)**, along with **10 NADH and 2 FADH2 molecules**.
* 🔗 ATP production in glycolysis and the Krebs cycle is termed "**substrate-level phosphorylation**," where a phosphate group is transferred directly from a molecule to ADP to form ATP.
* 🔗 The final stage of cellular respiration, the electron transport chain, will utilize the **NADH and FADH2** generated in previous steps to produce the **majority of ATP** through **oxidative phosphorylation**.
* 🔜 The next step in cellular respiration, the electron transport chain, will further utilize the **NADH and FADH2 molecules** to produce the **majority of ATP** through **oxidative phosphorylation**.

Let's pick up where we left off. So at the end of glucose, what we had as far as our carbon-containing compound, we have two molecules of pyruvate. Each of these is a three-carbon compound. Now, before we can move to the next step, which we're going to talk about just a minute, then the next major step. It's called the Krebs cycle, or another name for the same cycle is the citric acid cycle. But before we can do that, pyruvate cannot directly enter into the Krebs cycle, so it has to go through what you might call a preparatory reaction or prep step. And let's talk about this step. So we see here, here is one molecule of pyruvate. So this is going to occur for both molecules of pyruvate. And what has to happen is pyruvate, one of the carbons of pyruvate actually becomes oxidized so that

you're only left with a two-carbon compound, which is called acetyl or acetyl CoA. So the acetyl group is this portion here, which has the two carbons. Notice that one of the carbons, so pyruvate has three carbons, one of those carbons is the first instance we see of a carbon dioxide being released. So this carbon dioxide molecule, this carbon here [pointing to carbon in carbon dioxide] originally was one of the six carbons of glucose. And now we only have four carbons left. So in other words, for the two molecules of pyruvate, we get two molecules of CO2, one CO2 for each pyruvate, and therefore we have two acetyl CoAs. Okay. Kawase and so we only have a total of four of our original carbons from glucose. Now, I've mentioned already several times Kohei is short for Coenzyme, I remember when we talked about Inzunza, we said

many times enzymes need helpers, and so this particular is an enzyme helper or for the enzyme in the first step of the Krebs cycle. So it's necessary to carry this little group into the Krebs cycle. Now, the other thing I want to point out to you is we have the generation of two more molecules of our electron carrier in 88. So these are more electrons that are from the original glucose molecule. As we slowly break down those bonds of glucose, these Inamed molecules are accepting electrons to become an idea. So in the prep step, we need to keep track. We have two more molecules, and we get the first oxidation of carbon into carbon dioxide. So now we're going to carry back our acetyl COAS, we're going to follow them into the Krebs cycle, which is the main step that we want to discuss here. OK, get this, where we can see the whole thing, this circular process is what is known as the credit cycle or the citric

acid cycle. And so there's a lot going on. So let me point out to you what's important for us to understand. OK, first of all, this portion here is our acetyl CoA. This is where it enters into the cycle in this portion right here. So remember, for one molecule of glucose, we have two of these acetyl groups. I'm going to put a two right here. So in other words, we're going to follow this process two times, right. One for each acetyl group so we can multiply everything by two that we see being generated from one turn of this process. Now, remember that the acetyl groups each only have two carbons, so we have two of those, so we have four total carbons left from our original glucose molecule. The prep step, we saw that there were two carbons that were oxidized into carbon dioxide. So we need to see at the end of the Krebs cycle.

what do we get from these acetyl groups that are entering into the cycle? Okay, so what I want you to see is these two carbons from the acetyl group are actually being combined with this molecule right here called oxaloacetate. Notice that oxaloacetate has four carbons. Add to that the two carbons from an acetyl group and we get the first molecule here of the combined acetyl and oxaloacetate is called citrate, so four plus two is six. So we see that citrate has, in fact, six carbons. And now we're going to follow this through the cycle and count up what's what's happening to these carbons and what are we generating? Okay, well, first of all, we see here's a generation of an NADH molecule. In addition, we have the oxidation of one carbon into carbon dioxide. And the next step, we see the generation of another NADH and another carbon.

dioxide. Well, at that point, we only started with two carbons, right? The acetyl group or the acetyl group only had two carbons. And therefore, at this point, both of those carbons have been oxidized into carbon dioxide. Now, the rest of the process, the whole point is really regenerating the oxaloacetate that we sort of hitched a ride on to at the beginning of the process. There's a few other things I want to point out for you, though. We have the generation of it shows here GTP, so depending on the cell type, it may produce GTP or ATP for our purposes. We're going to count this as ATP just to keep it all in the same type of molecule, our energy currency to keep it the same. And this is the first time that we see this molecule called FADH2. This is similar to NADH. This is another electron carrier. OK. And we

finally, we have the generation of another molecule of NADH, another electron carrier. Remember, where are these electrons coming from that are being carried by NADH and FADH2? These originated right in the bonds of glucose. So as it is slowly being broken down, those electrons are being transferred to these electron carriers. So if we tally up all of that, OK, from one trip around the cycle, then we see there's three molecules of NADH, there's one molecule of FADH2, two molecules of CO2, and there's one molecule of ATP. But that's for one trip around the cycle. We have two acetyl groups, so that means two trips around the cycle. So we have to multiply everything by two because we're looking at it for an entire glucose molecule. So what do we get out of the cycle for one glucose? We get six NADH, two FADH2, four molecules of CO2, and two ATP. At this point,

all of the carbons of glucose have been completely oxidized into CO2 because the first two were oxidized at the prep step. That left us four, and all four of those now have been oxidized to CO2. Now, at this point, we need to tally up what we have at this point before we enter the electron transport chain. OK, so let's move and get us a fresh sheet here. So how many ATP have we generated? Well, we had two from Glycolysis, and two from the Krebs cycle, so we have a total of four ATP at this point. What about NADH? Well, we had two from glycolysis, we had two from the prep step, and then we have six from the Krebs Cycle, so we have a total of 10 NADH electron carriers. What about FADH2? The only place that was generated was in the Krebs cycle. We got two of those. Now, the final step in cellular respiration is

going to be the electron transport chain. And what we're interested in, at that point is what's happening to the electrons that these electron carriers are dropping off into the electron transport chain. So I want you to hold those. And in the electron transport chain, we'll see what happens and how those are used to generate ATP. But I want to mention a couple of other things before we move on, and that is the Krebs cycle is now occurring in the mitochondria and it does require oxygen. So without the presence of oxygen, the Krebs cycle does not occur. Finally, I want to visit with you for a minute about the way in which ATP is generated. From both glycolysis and the Krebs cycle, this is called substrate level phosphorylation and remember, an enzyme has a substrate and what this means is an enzyme is literally taking a phosphate. OK, from a molecule and it is bonding that or adding that phosphate on

to an ADP to produce ATP. So this means it's a direct transfer from one molecule to the next, mediated by an enzyme. That's how the ATP is generated in both glycolysis and the Krebs cycle. That's a very different process than the way that ATP is going to be generated in the electron transport chain. And the electron transport chain. It's called oxidative phosphorylation, and when we talk about that. I'll explain to you what that means, but I want to point out to you this big word phosphorylation, that essentially means adding a phosphate to a molecule. OK, so what are we interested in? Well, we're interested in adding a phosphate to ADP to get the high energy ATP. So substrate level phosphorylation means it's coming directly. It's being taken from one molecule and added on to the next. You'll see as we talk about the electronic transport chain that the way in which that ATP is

Krebs Cycle

Natalie Russell

Pyruvate, a three-carbon compound, undergoes a preparatory reaction to form acetyl CoA and release carbon dioxide.

This results in the production of two acetyl CoA molecules and two electron carrier molecules.

The acetyl CoA then enters the Krebs cycle to continue the process of glucose breakdown.

The acetyl CoA enters the cycle, with two acetyl groups for one glucose molecule, leading to a total of four carbons.

As the acetyl groups combine with oxaloacetate, citrate, a six-carbon molecule, is formed.

The cycle results in the generation of NADH molecules and the oxidation of carbons into carbon dioxide.

The acetyl group is oxidized into carbon dioxide, while the process focuses on regenerating oxaloacetate.

It produces ATP, GTP (or ATP), FADH2, and NADH as electron carriers by transferring electrons from the glucose bonds.

One glucose molecule results in the production of six NADH, two FADH2, four CO2 molecules, and two ATP through the cycle.

The Oxidation of Glucose and ATP Generation in Cellular Respiration

Glucose is completely oxidized to CO2 in the prep step, glycolysis, and the Krebs cycle.

Before the electron transport chain, 4 ATP and 10 NADH are produced.

The Krebs cycle takes place in the mitochondria and requires oxygen, while ATP generation from glycolysis and the Krebs cycle is called substrate-level phosphorylation.

ATP Generation: Substrate Level Phosphorylation vs Oxidative Phosphorylation

Substrate level phosphorylation is a direct transfer of a phosphate group from a molecule to ADP, mediated by an enzyme, occurring in glycolysis and the Krebs cycle.

In contrast, oxidative phosphorylation, which takes place in the electron transport chain, involves a different process of ATP generation and is known as oxidative phosphorylation.

This process adds a phosphate to ADP to produce high-energy ATP in a manner that is distinct from substrate level phosphorylation.