 Here everybody, Dr. O. So it's kind of done talking about what happens to pyruvate if there isn't enough oxygen, but now what about if there is, which is most of the time. So as you're going to see, this is called, you see the transformation step, I like to call it the intermediate step. This is where you take those two three-carbon pyruvates that were just created from glucose during glycolysis, and you convert them into two two-carbon acetyl-CoA. So a couple of things. Number one, if we're going from a three-carbon structure to a two-carbon structure we're going to lose carbon. Well, this is going to be where our first carbon dioxide is lost. You're going to see that glucose started with six carbons. When you fully oxidize glucose, you're going to get rid of all six carbons in the form of carbon dioxide. So you're exhaling the carbons that were in the food you ate or the food that is stored in your body, right? So that's the first thing. Then we have acetyl-CoA. So CoA comes from a B vitamin called pantothenic acid. You can't see it here, but CoA is massive, right? The acetyl group is this little tiny thing. CoA is this huge structure, but CoA is going to be this carrier, and it's going to play several of the roles. But so during the conversion of pyruvate to acetyl-CoA, there are zero ATP produced. So you're not actually making any ATP. But during this plot process, you're going to produce two NADHs. And you see here on the screen, one, but remember, since we split glucose in half, we're going to go through this process twice. So during the intermediate step, you're going to end up with two acetyl-CoA, and you're going to end up with two NADHs. And NADH, when we cash them in at our cashier, are going to be worth a total of six ATP, or three per NADH. All right. So that's going to be where acetyl-CoA comes from. I like to call acetyl-CoA the keystone of your metabolism. If you're burning glucose refuel as you can see here, fat for fuel, alcohol for fuel, or most proteins for fuel, they will actually be converted to acetyl-CoA first. Now once we have acetyl-CoA, it can enter our Krebs cycle, the most important part of this video. But once it's there, your body doesn't know. It's like, oh, this is acetyl-CoA that came from alcohol, this acetyl-CoA came from fat. It does not know, right? It doesn't know all the same thing when you get there. And that's probably why just to make, you know, clinically, if you're not consuming too many calories, right, or if you're a hard training athlete, the quality and source of your energy doesn't appear to matter that much, right? We get in the trouble if we consume more fructose than we need, or if we consume more carbohydrates than we need, for example. But if you're burning that fuel, like Michael Phelps, when they said he was eating 12,000 calories a day and most of it was kind of junk food, well, if you're fully metabolizing all the food you're eating, it's probably not as big of a deal. Because as long as it's being used, that it's not going into these processes where it's synthesizing things that you don't want around, like body fat, excess triglyceride in your blood, cholesterol, et cetera. All right. So now this acetyl-CoA has been, you know, this has occurred inside the mitochondria. So we have in us, in eukaryotes, it's already been brought into the mitochondria, which there was a price to pay for that, that we talked about in other videos, if this would just be happening in the cytoplasm of bacteria. But now we have the Krebs cycle. So you see acetyl-CoA at the top. And I'm not big. I like this image here because I don't care about the chemical structures. I know you might take some classes where they ask you to memorize them. I like to just primarily talk about some things that make it clinically significant. So here we see acetyl-CoA enters the Krebs cycle. Other names for it, the citric acid cycle, which is citrate there at the beginning. It's also going to be called the tricarboxylic acid cycle because that citrate has three carboxylic acids, not a big deal, or the TCA cycle. But I will call it the Krebs cycle or the Krebs citric acid cycle. So acetyl-CoA fuses with the oxaloacetate to make citrate. So the reason it's called a cycle is because the last step, the production of oxaloacetate, is needed for the first step. So it just goes on and on. As long as we have a constant supply of acetyl-CoA and we have enough oxaloacetate, then the Krebs cycle is just going to keep churning along. As far as clinical significance here, there are lots of B vitamins play big roles here. So if you're thiamine deficient, that would impact the ability of the Krebs cycle to work. Inflammation, too much free radical damage, that can hamper that conversion of citrate to isocitrate. There's little things like that all around the place. We'll actually talk about that more in another video about ketones as to why a higher protein diet makes it hard to produce ketones. But let's just go through the Krebs cycle and then I'll talk about what all the red words on the outside of the image mean. So as you run to the citric acid cycle, remember, you're doing it twice. So all the things you see on the screen here, it would have to be doubled. So you're going to make two ATP. See at the bottom there, you actually make two GTP and they're needed to make ATP. But we just say two ATP, that's fine. So you only see one being produced, but it's going to happen twice. So you make two ATP. But so those are the dollars that we can actually spend. But I like to use the analogy of casino chips. You're going to get a lot of money in casino chips during the Krebs cycle. You're going to produce a total of six NADHs, which are each worth three ATP. And you're also going to produce two FADH2s, which are worth two ATP. So during this step, we only made two ATP. What is that? 18, so we have enough energy now. We have enough stored electrons to make 22 more. 18 ATP from your six NADHs and four from those FADH2s. So critically important step, you don't make a lot of energy now, but when we go to the next step, the electron transport system, electron transport chain, you're going to have lots of chips to cash into the cashier there. All right, but what reason I picked this image to show you is because it doesn't just make energy. Your Krebs cycle is, I like to call it a metabolic hub. It can be used to catabolically break down fuel. And we've already said, whether you're carbs, lipids, proteins, or alcohol, you're going to end up in this cycle. So it can break down whatever you throw at it. So it's a great part of your metabolism. But the Krebs cycle also produces all sorts of things that can build stuff as well. So it is also anabolic, it also synthesizes things. So you see there, citrate can be used to make fat. So if you have a whole bunch of extra energy, then you see how, no matter where the energy came from, your body can generate fatty acids out of it. Some amino acids down here at the bottom, though, heme. So if you need to make more heme, to make more hemoglobin, to make more red blood cells, this could jump right off of the Krebs cycle and go ahead and do that. So those are kind of some of the best examples there, but just keep that in mind. I like to call this the metabolic hub, not just this catabolic metabolism center, because it does generate lots of very, very important things. So we'll come back and talk about the Krebs cycle again when we look at your ketosis and ketone production. But I just wanted you to see here that this is, so protein is a bit unique, whether alcohol, fat, and carbs are all going to become acetyl-CoA first. But if you look at the amino acids, if you're going to be burning protein for fuel, then you're going to, they can hop on in lots of different places. So I don't want you to be confused by that, but isn't just protein leads to acetyl-CoA. But as you can see here, aspartic acid can hop in and actually create oxaloacetate. Glutamine can actually lead to the creation of alpha-oketoglutarate there. So it's a little bit messy. Protein for fuel is a little bit messy because the amino acids and protein chains jump in in all sorts of places, but in the end, it still does use the Krebs cycle. All right, so that's the Krebs cycle where we generate a little bit of energy, but a whole lot of now fully loaded electron transporters are ready to go to our cashier. After this step, so we've done glycolysis, intermediate step, and now the Krebs cycle. We have, we've only made four ATP, maximum, but we now have 10 NADHs, the two from glycolysis, two from that intermediate step where we made acetyl-CoA and six here, and we now have two FADH2s. So if you add that up, we've only made four ATP, we now are going to cash in 34 ATPs worth of fuel, which will be the next video, the electron transport system. I hope this helps. Have a wonderful day. Be blessed.