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cover of episode Exercise Physiology | Bioenergetics (Making ATP) (Part 2)

Exercise Physiology | Bioenergetics (Making ATP) (Part 2)

2025/3/2
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Dr. Matt and Dr. Mike's Medical Podcast

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Dr. Matthew Barton
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Dr. Mike Todorovic
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Dr. Mike Todorovic: 本集节目讨论了人体如何产生能量(ATP),这是运动生理学系列的第二部分。我们首先回顾了稳态的概念,然后深入探讨了生物能量学,即人体如何利用燃料产生能量。我们定义了一些关键术语,例如新陈代谢(包括合成代谢和分解代谢)、ATP、酶以及氧化和还原反应。我们还讨论了细胞的结构,特别是肌肉细胞(肌纤维或肌细胞)的结构,包括肌膜、肌浆和线粒体。 我们详细解释了人体产生ATP的三种主要途径:磷酸肌酸途径、糖酵解和氧化磷酸化。磷酸肌酸途径是最快的途径,但持续时间很短;糖酵解是一种无氧过程,将葡萄糖分解成丙酮酸,产生少量ATP和NADH;氧化磷酸化是一种需氧过程,在电子传递链中利用NADH和FADH2产生大量的ATP。我们还讨论了在氧气不足的情况下,丙酮酸如何转化为乳酸,以及乳酸如何被肝脏重新转化为葡萄糖。 此外,我们还讨论了碳水化合物、脂肪和蛋白质作为能量来源的作用,以及克雷布斯循环作为所有代谢途径中心枢纽的作用。所有这些代谢途径最终都会汇聚到克雷布斯循环中,无论是葡萄糖、脂肪酸还是氨基酸,都可以参与其中。最后,我们讨论了有氧呼吸的效率(约34%),其余能量以热量的形式散发,以及棕色脂肪组织在产热中的作用。 Dr. Matthew Barton: 我参与讨论了新陈代谢的概念,包括合成代谢(构建)和分解代谢(分解)两个过程。我解释了细胞的基本结构,特别是肌肉细胞的结构,包括肌膜、肌浆和线粒体等细胞器。 在讨论ATP的产生过程中,我解释了酶的作用,它们是如何降低反应的活化能并加速代谢过程的。我还解释了糖酵解是一个无氧过程,不需要氧气参与,但在氧气不足的情况下,丙酮酸会转化为乳酸,以再生NAD+并维持糖酵解的进行。 此外,我还解释了氧化磷酸化是一个需氧过程,它利用NADH和FADH2将电子传递给电子传递链,产生大量的ATP。氧气作为最终的电子受体,接受电子并与质子结合形成水。我还解释了克雷布斯循环是所有代谢途径的中心枢纽,脂肪酸和氨基酸也可以进入克雷布斯循环参与能量代谢。最后,我解释了棕色脂肪组织在产热中的作用,以及解偶联蛋白如何减少ATP的产生并增加热量的产生。

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This chapter begins by posing the question of where our bodies get energy during intense exercise. It introduces the concept of bioenergetics and the importance of understanding fuel sources for energy in exercising muscles.
  • Bioenergetics: Fuel for energy
  • Focus on exercising muscles
  • Fuel sources for energy

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Welcome everybody to another episode of Dr. Matt and Dr. Mike's medical podcast. You are listening to our series on exercise physiology. I'm your host, Dr. Mike Todorovic.

Your attractive host, joined by my basic partner, Dr. Matthew Barton. How are you, Matty? Why did the gabber overheat? Why did the gabber overheat? All the fans left. All the fans left. I don't get it. Oh, okay. So, why would you tell a joke that requires explanation to the majority of our audience?

Including yourself, by the sounds of it. Yeah, well, I thought you meant Gabba as in the neurotransmitter. Okay, so the Gabba is Woolloongabba, and Woolloongabba is a suburb that houses Brisbane, which is the city we live in, the biggest stadium for football. So Matt's basically saying, why does this football stadium, what was it? Overheat.

Because the fans left. That's the worst joke I've ever heard. You know, that out of all of them, that's, that's the shittiest one you've ever done. All the Australian listeners would love that. They're laughing. They're still laughing. They're laughing at how stupid it was. Uh,

All right, ladies and gentlemen, boys and girls, friends and family, we are talking about, we are on part two of exercise physiology. First part, we spoke about homeostasis. So define some terms, spoke about the internal environment, how we maintain it. Now we're starting to talk about the bioenergetic, so fuel for energy. So we're going to, again, define some important terms here. We're going to talk about, so for example, Matt,

Shoot, shoot. I'm not going to have any. Put me down. No quip here, no smart, you know, smart quip. I just want to say, have you, it's hard for me to say, have you ever, God, have you ever pushed through a tough workout before? I'm not going to say it.

Have you ever pushed through a tough workout before and thought, where am I getting all this energy from? Constantly. I do it all the time. As you're spouting two liters of ice cream in your mouth. So we're going to talk about the fuel sources we use for energy. In the context of exercising muscles, because this series is on exercise physiology more so than that, right? Thank you. Thank you so much for that, Matt. Yes, that's correct. Okay.

We need to define some things in the front end. Do you agree? Let's do it. Define the front end.

Well, the beginning of the podcast, I would say. So first thing is metabolism. Can you define metabolism for us? Yes, I can. Two parts to this word. Again, the Greeks come up with this term. Good on them. We'll start with the suffix part of the term. So this is the bollock part. Is that a British word? That's not Greek. That's British. Bollocks. Okay.

So it essentially means to throw or to stroke or to cast. Okay. So when you put the front end of it being better, that's to change. Essentially what we're meaning here is... Wait, now say it together. A change throw, a throw of change. Yeah. So that really helps the audience. No, it doesn't much. So this is basically how...

Chemicals, molecules are modified in the body to be either broken down or built back up to keep our cells functioning. Okay. And if you build it up, what's the term we use? Anabolism. Anabolism? Anabolic. So if you use the term anabolic-

Like an anabolic steroid. It would be a hormone that would allow you to create more complex structures in the body, usually in the context of proteins. Right. And so what about when you're breaking things down? Catabolism or catabolic.

Catter meaning down. Not Bob Catter. Again, only a strange joke. Yep. Queensland specifically as well. So metabolism is a combination of catabolism and anabolism together. What's been built up and what's been broken down. So in the context of today being energy metabolism, what we're talking about here is certain structures that

That are going to be becoming more complex. Yeah. If we look at carbohydrates, sugars, we want to store them. That would be a process of anabolism. Yeah. Like glycogen. Whereas if we are trying to break them down, we're breaking down glucose into...

What does it get broken into? CO2? Yep. And ATP? Yep. A bit of heat? Yep. Okay. That would be catabolism. All right. So we've got building up, we've got breaking down. I always think about anabolic steroids. Bodybuilders take that to build up, right? Get more muscly. So that's how I remember anabolism. So we've got our metabolism is a sum total of building things up, breaking things down. All right. Great.

Easy definition. This is all happening now. We're focusing on, because in the past we've spoken about this sort of topic, but in the liver predominantly, right? Because we're talking about body metabolism, taking proteins, fats, carbs, utilizing it for energy and how the liver being the major site for this. But we're talking muscles today. Also muscles. So when we talk, so we've done episodes for our audience on cells, right? Yeah.

So very quickly, Matt, and I emphasize very quickly in this, can you just tell us the, because I'm sure our audience already knows, the important components of a cell and what they're referred to in a muscle, skeletal muscle. Oh, okay.

So how the terminology changes to the muscle. Is that what you mean? Okay. All right. So cell, we're a multicellular organism, which means we've got many, not just one, like a bacteria. Humans, we have 30 trillion odd cells. Now, the basic structure of a cell, so we would isolate one and just look at it generically, it would have an outer covering, which we'd term a plasma membrane. That's kind of as a barrier, but also dictates what can go in and out.

plays an important role there, sometimes termed semi-permeable. Yep. Then we have the inside of the cell, which is usually referenced because it's easy to see, and that's the nucleus, which I think means nut, kernel. Yep. And now that holds all our genetic information. That's, in today's context, going to be important to make proteins. Yep. Okay? And then we have the cytoplasm, which is the fluid part of the cell. Okay.

And that contains the organelles. And for today, some of the most important organelles that's inside a muscle is a mitochondria. Yep.

lots of proteins because a muscle cell, which we now term a muscle fiber is jam packed with heaps and heaps of proteins. A couple of points. One, you made a good one that a muscle cell is also known as a muscle fiber. They're the same thing, which is also known as a myocyte. So they're all synonymous. Next thing is that you need to tell us the, what the plasma membrane is called in muscle. Cyclema. All right. So what is the, um,

Cytoplasm called in a muscle cell. Sarcoplasm. Sarcoplasm, okay. What does sarco refer to? I think it just means flesh or flesh-like. Yeah, I think in Greek potentially. And you've also got other organelles like the endoplasmic reticulum, which we call the sarcoplasmic reticulum. And that would be...

equivalent to the smooth endoplasmic reticulum in a generic cell. And it basically just is a storage pool for calcium. Right. All right. And you're right. It's skeletal muscle just filled with contractile filaments.

Makes sense. And mitochondria. And heaps of nuclei, right? Because we need to make more of those proteins. Because it's constantly being damaged and needs to be repaired. The more nuclei, the more proteins. Perfect. Okay. So we've set that scene. And with the mitochondria, there's two, in a skeletal muscle, there's two general locations. There's locations...

Just under the sarcolemma? What's the sarcolemma again? That's the plasma membrane. So that's going to be... Why do you need lots of energy produced in organelles just under the membrane? Ooh, why is that? Well, you'd need a lot of ATP for membrane-bound processes. Oh, okay. Okay, and then all the rest of the mitochondria is around the... What would you call it?

into myofibular, well, filaments, which is all the contractile proteins. So you're going to have lots of mitochondria there for the contractile elements of the proteins. Brilliant. And the reason why we brought this up is because we're going to talk about metabolic processes happening in the cytoplasm, or I should say the sarcoplasm, and the mitochondria. Now,

A couple of things I want to talk about. First of which is that when it comes to energy, we need to understand energy transfer and then how energy is produced. And ultimately the end energy source that we want to discuss is ATP. So what is that? Okay, so ATP is adenosine triphosphate and it's made up of three things basically. The three things are adenine,

and three linked phosphates. So it's created by combining adenosine diphosphate with an extra phosphate, an inorganic phosphate. So let me just talk about inorganic versus organic. If you hear the term organic, it means what? Carbon. Yeah, there's at least one carbon present in

Inorganic? No carbon. There's no carbon. Did you do organic and inorganic chemistry? I did both, yeah. Next question is, was I good at either of them? I never really got organic chemistry. I felt like it was, I think I didn't understand it, but I felt like you just wrote learning like chemical structures and orientation and really understood the formula behind it. I just thought. Electron states. Yeah. Just know that that's what it is and just memorize it.

Yep. I was the same. I was the same. I had to relearn it when I became a quote unquote adult in order to be able to teach it appropriately. So yeah,

When we look at ATP, the phosphate that binds to adenosine diphosphate. So you've got three phosphates, hence why it's called adenosine triphosphate. You snap one off, it gives you adenosine diphosphate, so two. And the phosphate bond is a high-energy bond. So when you snap it, energy is released that –

in the body can leverage to do stuff, basically. So that's, we ultimately want to take the energy that originates from our sun and

And put it into phosphate bonds. Not your sun, the one in the sky. That's right. Not my S-O-N, but my S-U-N. Right. And so we need to be able to transfer that energy. So effectively, sunlight is utilized by plants to grow. Photosynthesis? Say that again? Photosynthesis? One more time. Photosynthesis?

Photosynthesis. Very good. The plants will, through the process of photosynthesis, take sunlight and put the energy into the bonds of the plant material. Animals will eat the plants. We will eat both the animals and the plants and the energy continually gets transferred into our foodstuff. Ultimately, proteins, fats and carbohydrates, the three macronutrients that we ingest. The whole point why we eat is...

is pretty much to generate ATP, or at least in this regard, which is going to be an energy currency for cells. Yeah, we need to transfer that energy into phosphate bonds, and we'll talk about that in a second. Now, the three fuel sources like I just alluded to – proteins, fats, carbohydrates –

Proteins aren't a big contributor to muscle energy. Maybe 2% to 12% of muscle energy is due to proteins. But they're important for building the proteins in the muscles. Yeah, they're important for the contractile proteins, but also for enzymes, which we're going to talk about in one second, enzymes and structural components of the body.

In addition to that, we've got carbohydrates and fats. These are important fuel sources for muscles. People think that fat isn't for muscle, but it is. Carbohydrates, it's all in the name. It's carbons that are hydrated. So carbons with water. So carbon, hydrogen, and oxygen, right? That's all carbohydrates are. Carbons, hydrogen, oxygen. In actual fact-

Proteins, fats and carbs are simply made up of carbons, hydrogens and oxygens bound together. In different orders. In different orders and in different quantities. And the only difference here is that proteins, in addition to that, have nitrogen.

So if you were to add up, so if I were to take your body right now and I were to pull you apart atom by atom, which has been a dream of mine, pull you apart atom by atom and separate the atoms into piles, 95% of you will be carbon, hydrogen, oxygen, and nitrogen. Just those four elements. And that comes from the foods that we eat, right? Yeah.

Now, what we want to do is take the bonds in those foodstuffs, snap them and transfer those bonds through electrons ultimately to the mitochondria to produce a lot of ATP. Okay. That's what we're going to try and get to today if I don't, if I, you know, shut up for once and stop going on and on and on. But let's talk about, because we need a couple more definitions, right? Enzymes. What is an enzyme? Because they're important for metabolism. Okay.

Uh, enzymes, I guess, uh, like trying to think of an analogy here. Proteins. Like a, like a, yeah, yeah. I was trying to think they like a sheep dog. It's like a NOS. It's like NOS. If you watch the, uh, uh, Fast and the Furious movies, you can drive a fast car. Oh, okay. Or you can press the NOS button and it makes that car. Speeds it up. So the car's already going to be driving. It's going to get from A to B, but the NOS gets it from A to B faster. Okay. How's that?

Yeah, it's okay. I prefer the sheep-dog analogy where the dog is the enzyme. It can round them up quicker. The sheep may get to the pen or to the wherever they're going.

As a group, but it will probably take a long time. Okay. But the sheepdog will feed them up. And with that analogy, then you can, by changing the environment of the sheepdog, it can make it more efficient or less efficient. And this is also important when you bring drugs into it. If you want to inhibit an enzyme from working. I was going to say bring drugs into the country. Then you can throw like a...

T-bone to the sheepdog and it gets... I have to say, I'm now lost with your analogy. All right, can I intervene? Can I intervene? So let's just say you need a process in the body to happen, right? That process will happen if...

and enzyme simply makes it faster. So it's not like not having the enzyme stops the process. The enzyme just allows for... And some processes need to happen very quickly. So there are mutations in enzymes that make you very sick and you can die. It doesn't mean that that process won't happen, but it'll happen so slow that it's not maintaining homeostasis in the body. So enzymes are required for many of these processes. And if you think about making ATP, it has to be fast. So we must have enzymes...

at pretty much every step of these metabolic processes. Now, the way I like to think about it, and I think it's Sisyphus who Greek mythology maybe was forced to push a, this is just memory, a boulder uphill for eternity, right? So let's say you're Sisyphus. You have a boulder that you need to push up to the top of the hill. Now,

Once you get to the top of the hill, it rolls down the hill. So that's the reaction you're trying to demonstrate. Okay. You could interrupt the... That's fine. It's not like I wasn't telling a story. I'm so sorry for talking while you were interrupting. I do apologize for that. Actually, I meant to be more mindful of my interruptions. So carry on. Oh, very kind of you. Carry on, Syphosis. So you're pushing this boulder to the top of the hill. And like you eloquently interrupted...

Once it's at the top of the hill and you let go, it falls down the hill, that's the reaction. You're totally right. But to get it to the top of the hill requires energy and that's called the activation energy.

Enzymes help you overcome that activation energy. So I see you pushing that boulder up the hill. I go, here, Sisyphus, let's put some wheels under this boulder. It makes it so easy for you to push it up the hill. So you're still going to do it. It just makes it faster and more efficient. That's how I think about enzymes. So it lowers that activation energy. Okay. Are you cool with that? I'm cool with that. No interruptions that you wanted to add? No, I'll wait till you're finished. Okay. And so enzymes, as we said, are proteins. Proteins are...

They've got a quaternary structure. What's that? So they are a line of amino acids. So proteins are made up of amino acids. That's their monomer. That's their kind of... Basic form. Yep. Depending on the sequence of amino acids will determine how they all fold in a secondary, a tertiary, and then sometimes more than one...

kind of line of protein comes together and joins as a whole multiple peptides so um

The structure of this protein will determine its shape. Therefore, the shape will then determine its function. And so with enzymes, like you said, what they usually do in terms of chemical reaction is they can either snap two substrates together to create a product or they can do the opposite, put a product and snap it apart into two substrates. And so the way that they kind of do that is they have usually an active site, a

region of the protein where the substrates can go in and bind together to allow that process or the chemical reaction to happen. Now, why I'm telling you this is because they're proteins, therefore, if you change their structure, that

that can alter that active site, then therefore it may not work anymore. So if you change its structure, you change its function. Correct. And how can you change its structure? Well, two of the most common reasons that you could do this or the two common ways you could do this in an exercise in muscle context is...

It gets too hot in there. So take off all your clothes. So the muscle gets really hot because you're exercising so vigorously. Therefore, as the temperature rises, the enzyme, the protein starts to change its shape. Therefore, the active site may not be...

That's a good fit for the substrates. You could also argue before you say the second one, if that's, if it's okay, that as the temperature goes up, it might for a short period of time, make the enzyme more efficient and work faster. But then you can hit a threshold where then it's like, oh, it's like, you know, when you exercise and your muscles are cold, right?

You're like, I can't really do this very well. But when your muscles are warm, you're like, hey, I can do this a lot better, a lot faster than when it's too hot, you're fatigued and you can't do anything. Enzymes are similar in that sense. Okay, so temperature's one. What's the other environment? The other big one is pH. So the...

the abundance of hydrogen ions. Yeah. And so that can also alter the structure of the protein. A bit like we've spoken before, like if you think of an egg, the white of an egg, that's protein, and to change its structure causes denaturing. We see that commonly by putting the egg onto a hot plate. The clear part then goes white, that's denatured. Or if you put it into an acid like vinegar, it would also do the same thing.

Similarly, if you change the environment of your muscle,

to either become too acidic or the temperature goes out of range, then the enzyme will start changing its structure, therefore its function, and it may not operate as well as it should. And that's going to impact, like you said, all these enzymes which are involved in glycolysis and Krebs cycle. Every step of the way. And so now the reduced ATP is hampered. Brilliant. Brilliant. God, you're good. So good. Is that enough compliments? Another thing, just while we're on enzymes before we move on. Oh yeah. If,

If you are happy for me to do this, there are some cases where you can use enzymes as diagnostic investigations. Such as? Well... So, I mean, in the context of exercise physiology? No, in the context of disease. Oh, okay. So, if you were to, let's say, have a heart attack...

there would be certain enzymes within your muscle of your heart, in this case heart, but the skeletal muscle also have it, such as creatine kinase. So a kinase, well actually I'll take one step back. With enzymes, we usually name them with an A's at the end. Whenever you hear A's, it usually refers to enzymes. Now, when you hear kinases, it's usually referring to enzymes that snap on or snap off phosphate atoms.

Is ion? No. Phosphate molecules. Yep. So whenever you hear a kinase, it just, that's what it means. Now,

A common diagnostic marker for potential heart attack is what we call creatine kinase. It's not as common as troponin, but that can be also used, creatine kinase. And what it's basically saying that these enzymes should be located in the cytoplasm of muscle cells. But if they become damaged, the membrane, which we spoke about, breaks and all these enzymes spill out. They can spill out into the blood and you can measure it.

The doctor can measure it and say, well, for some reason you've got high levels of creatine kinase. That must mean you've got muscle injury somewhere. Usually it comes after a bout of chest pain. You'd be confident it's coming from the heart. You've all just done vigorous exercise. You can also get it from muscles. Yeah, cool.

All right, let's have a chat about these fuel sources again before we jump into how we can make the ATP from them. So I said that proteins aren't a great fuel source, but carbs and fats tend to be. So you can get from one gram of protein, you can get four kilocalories of energy from it. Same with carbohydrates, right? One gram of carbohydrates, you get four kilocalories. What's a kilocalorie? A thousand calories? Yeah. Yeah.

Yes, but I don't even want to – it depends on whether you've got a capital K or a lowercase k. Let's just at the moment, let's just –

Think about it as being synonymous with energy. Okay. Regardless of what it objectively means, let's just say that carbohydrates from one gram you can get four kilocalories, same with protein, but for fats you can get nine kilocalories. So the point I'm trying to get across here is that you can get more bang for your buck from fats for energy than you can for carbohydrates. Now...

And that's simply got to do with the amount of bonds available to break from the fats. When we have a look at carbohydrates, you've got your basic most simplest sugar because carbs are complex sugars. And the simplest sugar is, well, there's three, glucose, fructose and galactose. Fructose and galactose can ultimately turn into glucose. So glucose tends to be the fuel source we often refer to.

So we think about that. Now, that glucose can be used to make energy in the muscle or the muscle can decide to store it. Now, what's it store glucose as? In the body? Yeah. No, in the mind. You did speak about plants before, so we could be doing... Okay. Let's talk... In animals? In our muscle. Glycogen. Glycogen. So glucose is stored as glycogen. Now, people ask how come we can't just...

Keep the glucose as glucose and just keep it as glucose. Increase our glucose levels. I say glucose a lot now. And the reason why is because glucose loves water. And so wherever glucose accumulates, water will follow. If you have heaps of glucose stored in your cells, what do you think that might mean? Well, it's...

Yeah. It'll change the... Osmotic gradient. Correct. Water gets pulled into the cells, the cells swell, not a great thing, can burst, all those problems. So if we snap the glucose together like Lego blocks, it makes it less osmotic, osmotically influential and active and can be stored better. And muscle is a...

storage region for glycogen, liver storage region, and also kidneys a little bit. But again, today we're focusing on muscle at the moment. So if I want to store the glucose as glycogen, that's called glycogenesis. That makes sense. Genesis means the beginning of. And if I want to break the glycogen up to bring it back to glucose to use to make energy, that's called glycogenolysis. So the lysis is the splitting apart. Now, if we look at fats...

When you say the word fats, people think of a lot of things, right? Generally fats are lipid soluble substances. So anything that can dissolve in fats or not dissolve in water, basically lipid soluble. So when I think of that, I think fatty acids, right?

What else do you think of? Phospholipids. Yeah, phospholipids and? Cholesterol. Yeah, steroids. Steroids. Right, and cholesterol is the major steroid, exactly. But when we're thinking about energy like today, we're just thinking about fatty acids, right?

And triglycerides. Now, similar to glucose being stored as glycogen, fatty acids can be stored as triglycerides. And that is called lipogenesis. And then if we split the triglycerides up to release the fatty acids again, that's called lipolysis. Right? That's pretty simple. Yep. All right. Easy peasy. So-

We've now got an ad. And what about proteins? Are we forgetting that? Well, we're forgetting that because it's not an important energy source. You can have protein synthesis or you can have proteolysis, right? So you can split it apart. I will touch upon using amino acids for energy in a sec.

But another take-home point, which I alluded to earlier, but I'm going to say again because it's really important. Proteins, fats, and carbs are all made up of carbons, hydrogens, and oxygens. Proteins have an additional, which is nitrogen. But effectively, when you want to use proteins for energy, you've got to snap that nitrogen off and turn it into urea and pee it out. But effectively, carbons, hydrogens, oxygens. The reason why fat is important

lipid soluble not water soluble and glucose is water soluble not lipid soluble simply has to do with the ratio of carbons to oxygens the carbohydrates have a greater oxygen to carbon ratio and the fats have a greater carbon to oxygen ratio and that just changes its solubility effectively right

Now, what we want to do is the sunlight, like I said, through photosynthesis has turned that energy, has basically pushed into the bonds through anabolism, allowing the plant to grow, right? We now need to snap some of these bonds to release the energy and transfer them. So-

We need to talk about how this happens to make ATP. So first thing is that there's three major pathways to make ATP, right? There's the phosphocreatine pathway, sometimes called the phosphagen pathway. There's glycolysis and there's oxidative phosphorylation. Okay. Right? So the phosphocreatine pathway, what do you know about that? A limited amount.

I've heard creatine before. Yeah. I've heard that athletes take creatine. Do you know what an athlete is? I've heard that creatine is... You've heard a lot, but you haven't read much. Who's telling you all this? Creatine is involved in very short bursts of exercise. Yeah. Have you heard anything else? No.

No, I'll leave it there at this point. Okay. You're correct. So whoever told you that was absolutely spot on. So when you – okay.

Right now, we know we need heaps of ATP to do everything, right? It's the major energy currency. It's not the only energy currency, but it's the major one. And we therefore need huge amounts of it across the day. Did you also say at one point today- Did I? Why we don't just-

ATP as ATP? I was just going to say it. Okay. I was just going to ask you the question that if we need so much of it, why don't we just like, you know, I just said there's three major pathways we use to make it. Because right now, if you were to do a high energy, I mean, God forbid, if you were to do a burpee, a single burpee. Catherine Johnson plotting the path for America's first astronauts.

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You're using it, your stored ATP. Like the stored ATP is done within a second, right? That's how quickly you use your ATP. That's how quick I would finish a burpee too. Well, I think 12 minutes later, you've done your first burpee. But again, I'm not, this is, this is not the podcast for me to tease. Okay. Um,

My point is you use your ATP very quickly, which makes no sense because we need so much of it across the day, particularly for exercise. Why don't we just store heaps? And that was the question you asked me. Well, a couple of reasons. One, it's a highly reactive and energetic molecule.

So you don't want to have a lot of it. Okay. Because... It could cause destruction to the cell, damage to the cell. Yes. And also because the way it regulates water similar to glucose. If you had a lot of ATP, it's going to shift water balance throughout the body. Not a great thing as well. So what we've evolved to do is those three mechanisms, those three pathways to create ATP in high quantities on demand. Okay.

So the first, which is the fastest, like you said, most immediate, but we don't have a lot of it, is the phosphocreatine or the phosphagen pathway. And the way that it works is that

When you use that ATP super quick, there's energy in that phosphate bond of the third phosphate, right? Adenosine triphosphate. Snap that last phosphate off, you've liberated energy for the muscles to contract, but now you've got adenosine diphosphate, useless, not good to us for energy. We need to replenish by giving it another inorganic phosphate.

We do that because we have creatine in our body. You get it through the meat that you ingest or supplements that you ingest, and it holds on to spare phosphate. So when you've used that ATP, it can hand an ATP over to regenerate ADP back into ATP. So does that then mean technically the first line of fuel is just a little bit of ATP that you have there all the time?

Yeah, the first one to two seconds of exercise is your stored ATP. Then you rely on creatine for the next 13 seconds. Pretty much, yeah. Which is just snapping phosphates off to enter the ADP to make quickly back into ATP.

Is there an enzyme that drives that process of snapping? Well, what did you say was the enzyme that handed... You alluded to the enzyme that hands phosphate over. That's kinases. Again, it's creatine kinase. Creatine kinase. That's the one we spoke about with the heart attack. There you go. So that's, like you said, it lasts like 5 to 15 seconds. So think about you doing a 10-meter sprint. Okay.

Right? Five to 15 seconds. But for a normal person, 100 meter sprint, right? Or if you were to go into the gym and lift weights, it's one set worth of energy, right? Just there for the phosphocreatine. Then we've exhausted it. You're not going to replenish that system until you rest. Oh, okay. So you need rest to replenish the phosphocreatine system. But let's just say you don't want to rest. Barton, don't rest, baby. Correct. Right? So...

What Barton wants to do is he wants to keep going. He's got more sets in him and he's just going to keep going with those reps. He's just going to keep lifting. I like where this is going. So next thing you know, ambulance is called. Matt's unconscious on the floor, clutching his chest. Not a good place for Matt to be. So he now needs to recruit another energy system to make the ATP and that's going to be now I

I know that I'm saying it as though it's happening in a particular order. All three of these systems actually happen simultaneously. It's just to what degree each one is happening most predominantly. The demands that's placed on it. Yeah. But it's always happening all the time. Yeah, that's right. But now you're starting to recruit or I should say rely more heavily on the glycolytic pathway or glycolysis. Now this is where we take glucose, that delicious basic sugar molecule and

And we ultimately will turn glucose into pyruvate. Now, glucose as a chemical structure is C6H12O6. Six carbon, 12 hydrogen, six oxygen. So it's a six carbon molecule. So to get this for digestion, you've just eaten a boiled potato. All right. Boiled potato. Yeah. I don't know. Is this your pre-workout? So everyone else takes...

Potato chips? Well, you spoke about plants. You banged down on plants in sunlight for the last 20 minutes. And so I'm trying to think about how is the plant storing its excessive glucose? Well, not as glycogen, but as starch, right? Yeah, that's right. So as a potato, yep. So it's put it as a potato. We've then cooked it up, whether you want to mash it or fry it or boil it. Who cares? So you digest it. What would you do? All three is fine with me.

but I definitely wouldn't do it for a workout. Anyway, so you've ingested the potato, you've digested it, broken it down. Glucose is absorbed across the intestine and now it's in the blood. So in the blood, it's going everywhere in the body. The first thing you actually need for it to get into your muscle, general,

generally speaking, is insulin. Insulin will come from the pancreas in response to rising glucose levels. Now, as soon as you, with the addition of insulin, allow the glucose to go into the cell, it now will descend down the glycolysis pathway. Beautiful. Yeah. No, that was a good preface. So,

Ultimately, there's 10-odd steps in this glycolytic pathway. We've done that. We've done an episode on that. So we're not going to focus on it because it's the same within each part of the body. But what we do want to highlight here is that glucose will ultimately turn into something called pyruvate. And like I said before, glucose is a six-carbon molecule and it needs to be rearranged

In order to be able to, one, snap into two to provide two, three carbon molecules, which is pyruvate. So from one glucose, you make two pyruvate. But in that process, what we need to do in the rearrangement is allow for the hydrogen, because remember, glucose is carbons, hydrogens, oxygens, C6H12O6, and pull the hydrogens off. Mm-hmm.

In the process of pulling the hydrogens off, you take two things, electrons and protons. Okay. So on the periodic table, let's see how good you are from your basic chemistry. What element is hydrogen on the periodic table? First one. That's the first one. Very good. So you at least remember the very first. Helium second. Keep going. No, that's it. Okay.

How far do you reckon I can go? Probably to the end. Yeah, probably to the end. No, I can't go to the end. I think I can go to 30-something, maybe. My daughter could go to 36 when she was three, unless she can't remember the first five. Isn't that depressing? Anyway. So...

We want to pull off the hydrogens because we're pulling off the electrons and the protons. Now, hydrogen as the first element on the periodic table, all it is is a proton, so a positive charge, with an electron, a negative charge. So if I were to take this hydrogen, if I pulled the electron off, all I'm left with is the proton. Now, that's why when you write on a piece of paper H plus hydrogen with a positive charge, you can call that a hydrogen ion.

or hydronium, right? Or you can call it a proton. So they're synonymous, proton and hydrogen ion, right? Because I plucked the electron off. That's really important to understand here. So when you turn glucose to pyruvate, the very first part, because you need to rearrange the glucose molecule, you actually need to invest energy into it. Now, Matt, if I invest energy into a reaction, that's got a name, right?

What's the name when you invest energy into a reaction? Endogonic. Yes, endogonic. Or endothermic. Is that right? Yep, yep. So basically taking in energy or taking in heat, right? And the reason why is you've invested the energy to allow for the rearrangement and now we can reap the benefits of that investment. So you invest two ATP to do this, but we get back energy

We make 4 ATP. At the end of glycolysis. Yeah, by the time we hit pyruvate. What do we, if we invest two but reap four...

How many net ATP do we make? Two. Okay, brilliant. Now, the other, so that's how we make, so I just said we've done the phosphagen system. You now need some quick energy through glycolysis. That's how you do it. You make the two ATP through that process. But you also do another bit of an investment here because we take two carrier molecules called NAD and FAD.

Now, NAD is nicotinamide adenine dinucleotide and FAD is flavin adenine dinucleotide. Now, NAD is B3, FAD is B2. Vitamin B3. Vitamin B3 and vitamin B2 is FAD, right? So this is why you read if you go to take multivitamins and you say, are the B vitamins are good for energy? It's because they play a role in metabolism such as these two molecules, right?

What they do is they carry molecules to pluck off the hydrogen, right? Now, effectively, we've rearranged glucose. We've reaped the benefit of two net ATP, but we're also now plucking hydrogens off. NAD will exist in its oxidized form. Now, we need to define this. We need to define this, right? So there's two terms that we need to talk about, oxidized or oxidation and reduction, right?

Oxidation, I remember my lecturer when I was an undergraduate, so this was 43 years ago, saying that, it wasn't 43 years ago. Thanks for correcting me. Everyone thinks that I'm very old. Well, I'm not very old. But anyway, 20 years ago, saying that Leo, right? L-E-O. So who's your favorite actor of all time, male or female? I never thought of that. It's Leonardo DiCaprio because I've seen the poster that you got in your bedroom. So L-E-O, Leo. So just think of Leonardo DiCaprio.

In Romeo and Juliet or Titanic? Hey, okay. Which one's better? Have you seen both? Yeah. Did you just bite your thumb at me, sir? I did bite my thumb at you, sir. Did you bite your thumb at me, sir? I did bite my thumb at you, sir. That's Romeo and Juliet, by the way. Lovely. With the petrol station. Yeah. And what about your favourite scene from Titanic? Is it where he's turning into an icicle while she's hogging the entire giant door that they could both fit on?

but decides not to let him on? Or is it the part where he holds her by the waist at the bow of the boat? Yeah, I think that. Is that because you always picture you and I? Yes. All right. Forming something similar. Yeah, yeah. At least it's not the one where he draws her naked and you... All right, so I can't remember. Oh, yeah, Leo, right? So loss of electrons is oxidation. So when a molecule loses these electrons, it's oxidized, right? Yeah.

Okay. That's called oxidation. So it doesn't have to do with oxygen necessarily. Great question. No, it doesn't. But oxygen is an electron acceptor. Okay. So loss of electrons is oxidation. Funnily enough, doesn't have anything to do with oxygen. Okay.

but oxygen is good at oxidizing things because it steals electrons. Okay. Right? That's an important, what would you call it, a reactant? Yeah, it's a final electron acceptor in this whole process, which is very important. But it's just interesting because presumably process oxidation was named because of the presence of oxygen. Yeah. I'm guessing, right? Yeah, because it can oxidize. Yeah. Yeah. Like you would say that...

Oxygen oxidizes a red blood cell. It's what you call an oxidizing agent. Yeah. Yeah. But let's not confuse people. Leo, loss of electrons, oxidation.

The gain of electrons is reduction, right? And this oxidation reduction coupling is important for NAD and FAD. So NAD exists in its oxidized form. So it's lost an electron. So it's NAD+, right? Because the negatives disappeared. So you're left with a positive, NAD+. Now what NAD plus does is it...

It goes to this glycolysis and it goes, all right, waiting for this rearrangement to occur so I can best steal some hydrogen. What NAD Plus does is it steals two hydrogen from this process. Remember, glucose is C6H12O6. There's 12 hydrogen it can steal. It steals two.

Now, when it steals the two, what it does is it steals a complete hydrogen. So that means the proton and the electron. So now it becomes NADH plus. And then it takes with the second hydrogen, just the electron from it. So it neutralizes itself. So it becomes NADH. So now it's in its reduced form because it's gained an electron, right? Yeah.

and then it releases a proton or a free hydrogen ion into the solution. Now, when I say that to you, Matt, where does your brain go when I say this process released hydrogen ions into the solution? Well, then the solution technically become more acidic.

Yeah, and that's what can happen when you undergo a lot of rapid glycolysis in muscle tissue, the pH goes down, right? It becomes more acidic because the hydrogen ion concentration goes up. Now, you've got NADH holding on to electrons and protons. That's important because in the third phase of making ATP, oxidative phosphorylation,

This is where NADH is required. But now we just spoke about glycolysis. We've produced two ATP net and produced two NADH. Brilliant. And two molecules of pyruvate. Perfect. Two molecules of three carbon pyruvate. All right. Let me stop you there just for one second. Yes, sir. You're going to go on to Krebs, I'm guessing. Yes.

Yes. Okay, but let me just stop you there. Please. Let's say at this point in time, we haven't required technically oxygen to partake in any of these processes. That's true. So the term we could use here is anaerobic. So you're saying glycolysis is an anaerobic form of ATP production? Technically speaking. Definitively, yeah. Yeah.

So if we... However the NADH needs oxygen to do its... Yeah, later on. Yes. But if I was to be exercising quite vigorously and I wasn't... So this is a dream. Yeah, that's right. And I wasn't able to deliver enough oxygen to my exercising muscle. That's not surprising. Can I do anything with peruvian oxygen?

to kind of go somewhere else instead of going into the mitochondria to go into Krebs and electron transport chain. So effectively what you're saying is because, so glycolysis doesn't require oxygen, right? So glycolysis,

Even if you don't have enough oxygen, you'll still undergo glycolysis to make that two ATP and the two NADH. Which I may say in 60% of your cells in your body, this is exactly what happens. Correcto. The red blood cells don't have mitochondria, so they will only generate their ATP through exactly that. Yes. Now, it's a fast way of making ATP, but you don't make a lot, right? Yeah. So-

Generally speaking, we don't want to do this forever. Like if you're going to run a marathon for, what would take you seven to eight hours? You don't want to be happy with that. Me too. I don't think I'd ever finish. You wouldn't just want to rely on glycolysis. Now, when we do this without oxygen, that's all good, but we are making the NADH, right? And

And that NADH needs to go somewhere. So technically we'll start building up in the cytoplasm. Yeah, it's going to build up. But ultimately what it wants to do is jump into the mitochondria and hand the mitochondria the electrons and protons it's stolen to make heaps of ATP. But to do that, that requires oxygen, which we'll talk about shortly. But just so we know, like you said, it needs oxygen to do it. But you said if we don't have enough oxygen...

that NADH accumulates. Now, if the NADH accumulates, it means that, remember, we started with NAD+. It stole the protons and electrons to make NADH. If we can't hand that electrons and protons off at the mitochondria, it can't regenerate NAD+. And we need...

more and more NAD plus for that glycolysis to happen to make the two ATP. So effectively without oxygen, you ultimately, you won't be able to make that two ATP. However, like you said, the pyruvate can go, don't worry about it. It's all good. I'll act like the electron transport chain. I'll steal the protons and electrons from you, NADH to regenerate you back into NAD plus. So you can keep undergoing glycolysis.

But what happens when the pyruvate steals electrons and protons, it turns into lactate, right? And so when people think about, oh, you know, I've just created all this lactic acid in my muscle, that's a bit of a misnomer because you probably haven't created all this lactic acid. You've created lactate. But if you look at lactate, it's, uh, it's, it's, uh,

pyruvate accepts protons so it can buffer. It basically helps to buffer out the solution. So it can make it less acidic effectively to create lactate. But what does that lactate do? When we create that lactate, one, it allows for glycolysis to happen. But where does that lactate go? Does it just accumulate and then that's it? Well, I don't think the muscle has, if we're talking about the exercise and muscle here, I don't think the muscle per se has the ability to

Reconfigure? Reconfigure lactate into something useful. Yeah. So what it can do is drop off lactate into the blood. Yep. And then lactate can be taken back to the liver, which is, you know, the body's selfish, selfless organ. Yeah. And remakes the lactate into glucose for you. And that's an important...

ongoing fuel source. Yeah, and you can measure somebody's blood lactate during exercise, right? That's what people do, looking at lactate thresholds and things like that. And also, because we spoke about oxygen levels, and this is anaerobic, if you were to be in a pathological situation where you weren't delivering enough oxygen to your cells, they would be doing this as well. So lactate is suggestive of things like

sepsis or heart failure because you're not delivering enough oxygen to the cells and then they have to undergo anaerobic respiration because they're not getting enough oxygen. Brilliant, brilliant, yeah. So I think that was a good point to highlight. So we've now spoken about phosphagen system and glycolysis. We now need to move on and talk about when there is enough oxygen present and oxidative phosphorylation. So now we're going from the two anaerobic pathways to the one aerobic pathway.

pathway, oxidative phosphorylation. So this will begin, well, we've already made NADH2 from glycolysis, but the pyruvate, the two three carbon molecules, the two pyruvate that we've made from one glucose needs to jump into the mitochondria and turn into acetyl-CoA.

Now, when it does that, it actually makes more NADH. Okay. Just that first process. Yep. Now, because we're turning two pyruvate into two acetyl-CoA, we make two NADH. So there's another investment. So let's take that investment away as well. So we've just made four NADH, two from glycolysis, two from pyruvate to acetyl-CoA.

The acetyl-CoA undergoes the Krebs cycle, also known as the citric acid cycle, also known as the tricarboxylic acid cycle. So it's got three major names. And effectively, when pyruvate turns into acetyl-CoA, it goes from two three-carbon molecules to two two-carbon molecules. It's just lost carbon. Where does that carbon go? I'm guessing exhaust fume. Oh, okay.

And what's the human exhaust fume? Carbon dioxide. Carbon dioxide. Exactly right. And this is why. So think about it. Proteins, fats, and carbs made up of carbons, hydrogens, and oxygens. NAD and FAD continually pluck off the hydrogens, leaving carbons and oxygens. So through this process of metabolism, we are just continually left with carbon dioxide, the fuel source of metabolism. I think that's beautiful, right? Where does the CoA come from?

The CoA is added through another B enzyme. So there's another B vitamin that comes into play to help add the CoA. And it just, CoA, you usually, and this is a bit of an oversimplification, anytime you need to shuttle one of these metabolic molecules, you need a CoA. Okay. Right? So the shuttling of the acetyl CoA

It needed the co-a for the shuttling movement. Okay. Just makes it easier to move across places, generally speaking. So...

The acetyl-CoA undergoes the Krebs cycle. Now, this is a cycle in which it goes from being too carbon, it adds carbons back and so forth. But at the end of the day, it produces just one cycle of the Krebs cycle, one GTP molecule. Okay, so that's kind of equivalent to one ATP molecule? Yes, exactly right. So it creates one GTP molecule, three NADH molecules. Okay.

And one FADH2. Now, I haven't spoken about FAD at all. So I said that in glycolysis, we use NAD plus to make NADH. And in the citric acid cycle, we take FAD, which is still its oxidized form, and it steals two hydrogens, just like NAD did,

But this time it still is two complete hydrogens. So it turns from FAD into FADH2. Right, okay. So it doesn't release a proton into the solution like NAD did. But still, it's carrying electrons and protons, right? So...

The whole point of this, of the Krebs cycle, yeah, we produce a little bit of ATP in the form of GTP, just another type of ATP. Think of it as synonymous with ATP. But we're now carrying electrons and protons, two from glycolysis, two from pyruvate to acetyl-CoA,

Because one glucose gives us two rounds of the citric acid cycle, that's six NADH and two FADH2. Right. We've got a bunch now. So effectively we've got, what's that? We've got 10 NADH and two FADH2 being carried to the electron transport chain. What it does at the electron transport chain is it dumps off the electrons and the protons. Okay.

And what will happen is the electrons will excite proteins embedded in one of the membranes of the mitochondria. Now, the mitochondria is different to other cells, right? Because the mitochondria was a bacterial cell. So can you just tell people a little bit about the structure of the mitochondria? Well, the mitochondria, unlike our cells,

cell membrane, which is a bilayer, like a plasma bilayer. It's actually got two membranes associated with it. So an outer membrane and an inner membrane. Doesn't a bilayer mean two membranes? Yeah, but it's just kind of incorporated into... So

So the phospholipid bilayer is a single membrane. Single membrane, but it's just got two sides to it. Yeah, okay. Whereas a mitochondria has got two membranes. Right, so it's got four sides to it. Four sides. But let's just say two membranes. Yeah, that's right. So it's an outer one and an inner one, and then the inside of the mitochondria is what we refer to as a matrix.

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Thank you.

Right. The, what would you call...

the space between the two membranes. Oh, yeah. So if you've got an adult membrane and then another membrane within that, you've got a space between the two. I would call that the intermembrane space. Okay. That's important to note because that's where all the protons are going to go. Okay. But embedded in the inner layer are all these structures. Most of them are proteins, but I think there's one lipid there, right? Yeah. Biotichrome Q.

Is that right? Coenzyme Q. Yeah, coenzyme Q, which I think is more so towards the intermembrane space, but yes. I think that one plays an important role potentially with statin medications. Oh, okay. Because that's where statins may interact with them and then that's how some people get muscle soreness or muscle breakdown. Oh, interesting. So these coenzymes are...

mostly proteins, but there are, as I just said, a lipid. And they also, some of them have an association with metals like iron and sulfur, I think. And that helps with the electron. Right, right. So really what these, I actually didn't answer what you want me to do. So the thought here was, if you look at a bacteria cell, bacteria generally will have,

Two membranes and... Like a mitochondria. Yeah, and like it will also have a wall. Oh, so it has cell membranes and a cell wall. Yeah, and so sometimes you can distinguish between...

gram-negative bacteria and a gram-positive bacteria. Because of the presence of a wall? The type of the wall. I mean, a gram-positive bacteria usually has a larger wall, whereas the gram-negative is smaller. But they still have the membrane associated with it. So the thought here is that this once operated as a

independent bacteria. But at one point in animal evolution, this was incorporated into the cell and they kind of worked through a symbiotic relationship that bacteria would produce energy for the cell and the cell would give it what it needed. Yeah, perfect. And I think you're right, when we're both single-celled organisms, we sort of merged together and grew and evolved. So

What we've done is the NADH and FADH2 will dump off the protons and the electrons to the inner membrane where these proteins are embedded and passes the electrons to the cytochrome proteins. And because electrons are really, well, they are excitable, what would you call an electron? A subatomic particle. Yeah, yeah. Electrons like to...

interact with things, right? And so when you hand an electron to a protein, it excites that protein. It can't hold it for very long because it will damage it, but it excites it. And so when you hand the electrons off to the first protein in the chain, it excites it. And it excites it so much that it allows for the protons to be pumped up into that intermembrane space between the outer and inner membrane. And

And then that cytochrome goes, oh, I've had enough of this electron, passes it off to the next, right? Like hot potato. So as it passes these electrons off, the proteins get excited, keep pumping protons into the intermembrane space. We've now developed a proton gradient. We've got huge amounts of protons in the intermembrane space. Because of diffusion, it wants to go back down its concentration gradient and it does it through a channel that's associated with an ATP synthase. So basically like a...

like an aqueduct or like a, uh, yeah. Like, so you've pumped, uh,

Water up a hill into a dam. Yes. And then you've released it down its gradient to drive a turbine. Yes, perfect. And that turbine that the protons are spinning, and they literally spin it. If you look down at an electron microscope, you see that as the protons move down their gradient, it spins a turbine that makes ATP, and it makes huge amounts. So effectively, for every NADH,

you create 2.5 ATP. Okay. For every FADH2, you create 1.5 ATP. So we could do the... Can we do the maths quickly here? From the start to finish? Yeah, very simple. Okay, so...

Glycolysis, we made two net ATP and two NADH. So the two NADH, if you times that by 2.5, because it makes 2.5 ATP, and add two ATP to it, you get seven ATP for glycolysis. So keep that, seven ATP. You turn pyruvate to acetyl-CoA, that made two ATP, times 2.5, that makes five ATP, right? So seven plus five is 12 ATP so far.

Then in the Krebs cycle, we've made two GTP. So that's 14. We made six NADH times 2.5. That's 15. Right. So what's that already? That's 31. Yeah. Right. Uh,

Then FADH plus, I'd put two, sorry to say. Yeah, FADH2 times, so we made two of those, times 1.5, that's three. We end up making between 32 to 34-ish ATP molecules. Total, yeah. Right? Per glucose molecule. Per one glucose molecule. Now, here's the thing, but we need oxygen for this whole thing to happen because...

So for example, if you and I were playing hot potato, right? This potato is super hot. Let's say that you and I were the, I was the second last person to catch a potato, but you're the last person. So all these people are passing the potatoes. It's bloody hot. So I throw it to you. You've got no one to pass it to. So either you burn the crap out of your hands, right? So damage yourself. Or you've got to find someone to pass that potato to.

So luckily there's a bin next to you and you pass the potato, throw the potato into the bin, right? Now that bin in this case is oxygen. It's a bit harsh on oxygen calling it a bin. It's rubbish. So the oxygen is the final electron acceptor. It takes the electron and electrons and

And that makes it O negative, right? Because you've just taken a negative electron. But luckily there's heaps of positive protons that it can also bind to. That's coming from the dam, so to speak. Exactly. So now when you mix negative oxygen, negative O with positive H, you get...

Neutral water. Lovely. Beautiful. Isn't that perfect outcome? So we make water from this whole product. And that's only if the oxygen is available. So if that oxygen isn't available in sufficient quantities, like you said earlier, it all backs up. The NADH accumulates. And what that means is it's a negative regulator. So here we're going to start talking about negative regulators, right? So if you've got too much NADH, it's going to back the whole thing up. Yes. It's inhibitory, right? Yeah.

But that's in the case of not enough oxygen. So what you said we did was the pyruvate took the NADH, regenerated more NAD plus and made lactate. That's like a pressure valve really. Perfect. Just to allow you to still make enough ATP to...

But this is obviously demonstrating it's a much more efficient way of producing ATP. Yeah, you make heaps more, right? Now, if, so let's just say, let's just say you do exercise, right? And you're taking, you've got all this fuel, you're making ATP, you've used your phosphagen system, you've used glycolysis and you've used aerobic respiration. We've only spoken about

in this process, right? Oh, yeah. But we said there's fats and even to an extent proteins. So the great thing is...

The Krebs cycle is the center point, the linchpin of all of metabolism. All roads lead to Rome. Beautiful. That's right. All roads lead to Rome. All metabolic pathways lead to Krebs cycle. So not only does glucose jump into the Krebs cycle, but you can take fatty acids from triglycerides and throw it into the Krebs cycle. Well, the triglyceride breaks into two parts, doesn't it?

So you break into the fatty acids, but also the glycerol. The glycerol portion will feed back into glycolysis and the fatty acids will go into acetyl-CoA. Perfect, yes. So the process of, you know, we said earlier when you break down triglycerides, it's called lipolysis, right? Now, like you said, when you release the fatty acids...

The fatty acids can turn into acetyl-CoA. That's called beta-oxidation, that process, and it's an extensive step-by-step process. But effectively, certain length fatty acids can turn into acetyl-CoA and jump into the Krebs cycle. And like I said, the glycerol, which is the backbone of triglycerides, jumps into glycolysis. So that's great. So it's perfect how it jumps in. Proteins can break into amino acids. They

They can effectively jump in as a Ciro Coe. They can jump into multiple steps of the Krebs cycle and they can even jump into...

to some degree, glycolysis. So amino acids can jump in at multiple steps as well. So the great thing is that the Krebs cycle is the center point in which all nutrient types can jump in. Beautiful. To supplement whatever needs to happen. Now, if you had enough ATP, let's just say you produced, you'd done your exercise, you'd produced all the energy you needed and then you rested, right? Yeah.

your body will accumulate more ATP than it needs, more NADH and FADH2 than it needs, and it will have generated heaps of acid because of the hydrogen ions that have spilt over, right? All of these things are negative regulators for everything we've spoken about. All those enzymes that...

The following step took her. Yeah. Yeah. So they all feedback negatively, which makes sense. Like a lot of homeostasis is the end product negatively. So like last episode, we spoke about homeostasis. The end product will negatively regulate upstream. Total makes total sense. And the opposite is that if you have a lot of ADP,

it says I need energy so that positively regulates upstream if you have a lot of NAD plus positively regulates upstream if your pH is higher it positively regulates upstream so

So the flip side is also correct. So these are some major regulators as well. Now, I've got an interesting fact here and I want to see what you think, right? So you can calculate the efficiency of aerobic respiration at making ATP, right? So meaning of if I were to take a certain amount of glucose, right?

the total possible energy that can be made from that glucose, how much of it actually turns into ATP? Do you have any idea? How to measure it? No, just as a percentage. Like of the total possible amount of energy that can be made from a glucose molecule. The fuel source? Yep. Glucose specifically. So if you look at...

The amount of possible calories. So if you look at petrol. Oh, here we go. This isn't a fuel source that you're utilizing, I hope. No, but it underscores, I think, what you're trying to say here. So if you use petrol, which is a hydrocarbon. Okay, yeah. But it's utilizing. Still don't use it. It's utilizing. So in your engine, in your car, you're utilizing it to generate work. Yes. Okay. But it's generated in a exothermic or exergonic means. Yep.

but in a combustion. So it's kind of like an explosion, but all happens in one go. There's a lot of heat there. So I think it loses a lot of energy through heat. Petrols are something like 23%. I can,

Please correct me. I'm not going to correct you. I have no idea. Listeners, correct me. I think diesel is slightly more efficient. Yeah. But then when we go to... When you say efficient, you're saying that... You get a bit more energy. When you burn it, you're using... You end up using 23% of the total possible energy... Correct. ...to push the car, to move the car. Yeah, that's right. All the rest will go in heat and light and I guess...

non-used sources and then that's the exhaust fumes and so forth. Okay, so I'm doing it. I love this. The only thing that's different, I'll just say in the human body is we don't do combustion style chemical processes because you'd blow your cells apart. So we do our exergonic

Very stepwise. So this is why we've got 10 steps to glycolysis. That's right. That's right. It's not just like, boom. That's right. Exactly. Okay. That's a good point. So that's my original question. I would be guessing 60% or something. 60? Yeah. A lot lower.

So it's 34% of the total possible ATP that you could get. You only get 34% from a glucose molecule through aerobic respiration, right? So that's going through aerobic respiration. The other 66% is heat. Wow. Right? So this is why your muscles very quickly get hot when it's making ATP and being used.

And hence why that heat needs to dissipate through the bloodstream. And while your blood vessels dilate, you get very red because you're making three times as, no, sorry, twice as much heat as your energy, utilizable energy from the muscles. Isn't that cool? It is cool.

That's all I've got because in future episodes, we're actually going to go through more of the specifics, hormone regulation, metabolism, going through the specifics of the pathway. Just one thing with heat, just to underscore just one kind of interesting principle there is when we go back to the electron transport chain, so the final stage of generating ATP,

And you spoke about the series of proteins that they do the hot potato with electrons. There is parts of, I mean, it's not that common in adults anymore, but in children, babies, they have a type of fat protein

called a brown fat. You've heard of this? I have, yeah. I believe in the book that you and I both wrote, there's a chapter about brown fat. Yeah, we do go through the different types of fats in the body. So the white fat mixed brown and then the locations subcutaneously or visceral and how they do different things. But with brown fat, you probably heard that this has a role in thermogenesis. Yes. So it does...

supply temperature regulation for the baby because it's its ability to regulate its own temperatures or at this stage right so what's this good to the mitochondria sorry the the proteins yeah so the proteins what it does is it will actually uncouple one of those hot potato processes oh okay and so it kind of stops it continuing on and

And so you'll still have its ability to kind of move things along, but instead of driving the turbine, it kind of stops. It reduces the efficiency for ATP, but increases the heat. The heat. Oh, that's very interesting. And so this also occurs with some animals that hibernate, and this is how they keep warm during the winter months. So do you know if they accumulate more oxidative stresses?

Oxidative free radicals? Not sure. So the point I'm asking for our dear listener is that because the electrons are so reactive that if you don't have a good terminal acceptor like oxygen, it might be taken by other molecules. It can include oxygen but other molecules and it can create reactive oxygen species. Yeah, and this would be the –

Yeah, this is where you talk about antioxidants, right? Yeah. On account of those. Yeah, that's right. And this is where like vitamin A comes in to help reduce these oxidative stresses that are produced in this instance and so forth. But if you've got uncoupling happening of the mitochondria, it can lead to an increased reactive oxygen species. Yeah. Interesting to know that. Well, this is one of the theories in- Aging? Aging.

Both aging but neurodegenerative diseases. So I remember when I was doing my PhD in Parkinson's disease, you know, this is 15, no, yeah, 15 years ago I suppose. Jeez. They were talking about

how there are proteins that are associated with the mitochondria, which effectively uncouples it and you accumulate reactive oxygen species. And because the neurons are very susceptible to reactive oxygen species, that it, and often reactive oxygen species can lead to like a cascading event where it

disrupts one, makes it a reactive oxygen species, disrupts the next, makes it a reactive oxygen species and continues to sort of snowball. Snowball, exactly. And that's what they thought. And so I think that that may play a role in Parkinson's and Alzheimer's and certain neurodegenerative diseases. That was just a little aside for people. But that, Matt, was bioenergetics.

within exercise physiology. We will be doing more parts. The next episode we're going to be doing is exercise metabolism, which is going into more detail. Can you believe it? More detail of what we've just spoken about. And we'll also be looking at the hormonal regulation of metabolism as well within the context of exercise physiology. So Matthew, thank you for that, my friend. Can the dear listener please give us a five-star review, leave a positive comment,

send us an email at admin at drmattdermike.com.au. You can go to our website and send us an email through our website, drmattdermike.com.au. You can follow me on social media, drmiketorovic, D-R-M-I-K-E-T-O-D-O-R-O-V-I-C, on all good and bad, most of them social media platforms.

And yeah, we're going to be releasing a book towards the end of this year. And as we approach its release, we will start to increase the hype and we'll talk more about it. And we might even give you some taste of some of the chapters and so forth, but watch this space. And when we do release the book, please buy it. We'd really like that. And Michael sign up for you. I will, I will sign up for you. That won't.

Because you still need to learn. We'll have to do a world tour. Oh, that's true. We do have to do a world tour. And we actually have a lot of emails to catch up on. So we need to do a Q&A. We'll do that next week. All right. Thanks, Matt.

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