Tissue specific metabolism and the metabolic states
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- At9:45the speaker stated that triglycerides are broken down into glycerol and fatty acids and are eventually used to make more glucose. I thought fatty acids cannot contribute to glucose production unlike amino acids and carbohydrates. They contribute to acetyl CoA production instead. Am I missing something here?(12 votes)
- Only the odd-chain fatty acids can be oxidized to yield propionyl-CoA, a precursor for succinyl-CoA, which can be converted to pyruvate and enter into gluconeogenesis to make glucose. Even-chain fatty acids like Palmitic acid can only yield Acetyl-coA.(14 votes)
- I am confused I thought it was mentioned that Fats don't contribute to creation of glucose in a past video. But here at8:59he says that Fatty Acids are converted into glucose? WHAT?(7 votes)
- I can't see most of what you're writing. can you use a bolder writing tool? thanks.(6 votes)
- I think the speaker could use vocabulary such as "and undergo gluconeogenesis" or "anaerobic respiration" to connect concepts from other videos(5 votes)
- This video was originally designed for nurses. Level of scrutiny is much higher when his audience is studying for the mcat lol(2 votes)
- Having watched the oxidation videos leading to this point I believe this drawing is perfect. It gives you the big picture idea without going into the level of detail that was used in earlier videos. This helps tie in the small details to the big picture process.(2 votes)
- Can the brain use ketone bodies? I thought the idea was that ketone bodies are used in the fasted state the allow the brain to use the glucose that is present in the body. In other words, the production of ketone bodies sustains most of the body's cells other than RBCs and the brain, which (exclusively?) use glucose. Now that I type this out, I think that RBCs must use glucose because they do not have any mitochondria and must do glycolysis, but what can we say for the brain? Can ketones cross the blood-brain barrier?(2 votes)
- In extreme post-absorptive states, as in starvation, the brain can partially use ketones as a fuel source (~up to 2/3s of its metabolism). Under normal conditions, it solely uses glucose, with ketones being an emergency backup. On a side note, triglycerides are unable to cross the BBB.(1 vote)
- How can the liver break down fatty acids in the post absorptive state when all of the fatty acid is packaged into VLDL and sent to adipose tissues?(1 vote)
- During the post absorptive (fasting) state, the adipose tissues will convert triacylglycerols to fatty acids (and glycerol) and ship them off to muscle tissue and the liver through the blood with the help of serum albumin as a result of decreased insulin and increased epinephrine levels. The liver receives the fatty acids and that is what provides the necessary carbon skeletons and energy required for gluconeogenesis in the liver.(2 votes)
- How does the Alpha-keto acid helps in the making of glucose?(1 vote)
- At10:23, I think it should be worth noting that the glycogen converted to glucose in the muscle cell cannot enter the blood. Lactate and pyruvate (via glycolysis), however, can.(1 vote)
- in the absorption state you didn't talk about lipids what happens to absorbed lipids in the liver and adipose tissue? and what happens to other substances (atoms) like Calcium or Potassium?(1 vote)
- [Voiceover] When I look at this image, I'm not exactly sure what I see. Am I looking at a diagram that shows all the metabolic pathways in the human body, or am I looking at a map of the subway in New York City? Now, in order to describe how the body balances the storing and utilization of energy through different nutrients in all the tissues of the body, I'm gonna just go ahead and get rid of this diagram. And I'm gonna bring up one that's a little bit more simple. Now, this isn't exactly an anatomically correct diagram, but it'll work to describe how these different tissues function metabolically. First, let me bring in some metabolic intermediates. And, I don't want you to get overwhelmed by all of these intermediates, as there are quite a few of them, 'cause we're gonna be going through each one of them individually in order to make sense of this entire diagram. Now the first metabolic state I'm gonna talk about is the Absorptive State. Well, the Absorptive State is a series of metabolic reactions that your body does when food is in plenty, you have food in your intestines, and you're absorbing that food, and so you don't need to utilize all this energy. Instead, you want to store it, so you can use it later. So what is this series of metabolic reactions look like in the Liver? So imagine the Carbohydrates are broken down in the intestines, and you're absorbing the di- and monosaccharides like glucose. So glucose is then transported to the Liver, and it can have one or two, kinda go in one or two pathways. The first pathway is that it can be stored as glycogen. I circled and filled in glycogen here to remind you that this is the storage form of Carbohydrates. The other way glucose can go, is to be converted into Triglycerides, which are the storage form of Fat. Now in order to do so, the glucose must first be converted into glycerol, as well as Fatty Acids. And the process of converting glucose into Fatty Acids involves going through Pyruvate and Acetyl CoA, to form the Fatty Acid known as Palmitate, which is the only Fatty Acid that the body can synthesize on its own. And then these glycerol and Fatty Acids can be combined to form Triglycerides. Now in the Liver, we don't store Triglycerides. It's stored mostly in Adipose tissues, and Triglycerides can't be transported in the blood. So these Triglycerides have to be converted into very low-density lipoprotein, or VLDL, which can then be exported out of the Liver, and into the blood. Next we have the Amino Acids that are contained in Protein, so the meat we ate in our cheeseburger is broken down into Proteins that are then broken down to their component Amino Acids, and these Amino Acids are taken up by the Liver. The Liver will break them down into Keto Acids. And these Alpha-keto Acids, when we break them down they're gonna give off ammonia, which is then excreted as waste, in the form of Urea. So these, the energy that was in the Amino Acids is now in our Alpha-keto Acids. Now where can this go? And it can also go one of two ways. If we want to store the energy that's in these Keto Acids, we're gonna convert them to Fatty Acids, and those Fatty Acids can then be converted into Tryglycerides, and those Tryglycerides would be once again exported into the blood, and then later, we'll store them in the Adipose tissue. But if the Liver needs energy during this Absorptive State, these Keto Acids can also be broken down into Acetyl CoA, and that Acetyl CoA can go through the kreb cycle and electron transport chain, to produce ATP, or usable energy. Now let's move on to Adipose tissue. So Adipose is Fat, and Fat can kinda be thought of as just a vast, a warehouse of energy storage. So when we eat, the carbohydrates are broken down, and the glucose is transported in our blood to Adipose tissue, and it's taken up. And in the Absorptive State, this glucose in Adipose tissue is gonna be turned into Triglycerides, but first, similar to the Liver, it needs to be converted to glycerol, and Fatty Acids, and then the glycerol and Fatty Acids are going to be converted into Triglycerides. However, this isn't the only thing that's happening in the Adipose tissue during the Absorptive State, remember we exported those very low-density lipoproteins from the Liver, well those are now gonna come down through the blood, and they're gonna enter the Adipose tissue and be turned into Fatty Acids, and these Fatty Acids can then be combined with glycerol to form Triglycerides. And similar to above where I circled and filled in glycogen, Triglycerides are now circled and filled in because this is now the storage form of our Fats, and it's stored in the Adipose tissue. So let's move on to the Muscle. What's going on in the Muscle? Well, once again, just like in the Liver and in Adipose tissue, glucose is taken up by the Muscle cell during the Absorptive State, and glucose can now have one of two pathways. Similar to the Liver, we can convert it to it's storage form in glycogen, but also, the Muscle may need energy, even though, in general our body is storing energy in our storage forms, it sometimes, during the Absorptive State, it still needs to utilize some of this energy that we've eaten, so that glucose can be converted to Pyruvate, and through cellular respiration, we can create ATP, and the Muscle will have usable energy. And in the Absorptive State, Muscle also takes up the Amino Acids from Proteins that we eat, and these Amino Acids are just stored as Protein in our Muscle. Now let's talk about the Brain. So, in the Liver, Fat and Muscle cells, the primary actions of the metabolic pathways during the Absorptive State was to store energy. To store energy as glycogen, Triglycerides, and Protein. But in the Brain, we don't store energy, the brain consumes a vast amount of energy. So during this Absorptive State, even though generally, the body is tending to store energy, the Brain is just gonna use it. So the glucose from the blood is taken up, and it's converted to Pyruvate, and just like in the Muscle we talked about, it goes through cellular respiration to produce ATP, so that the Brain can continue to do work. So as you look at all of these metabolic pathways during the Absorptive State, it makes sense that, when the body has abundant energy, because it's just eaten that we're gonna store that energy. But what happens when we haven't eaten in a while? When our body needs to take the energy that's stored in glycogen and Triglycerides and Protein, and use it? Well, that's what happens in the Post Absorptive State. So, for a moment here I'm gonna just remove the Absorptive State from our diagram. So now our body has absorbed all of its nutrients from the gut, see there's no longer any Fat, Protein or Carbohydrates here, and we've stored it in its respective storage forms, in the Liver we've stored Carbohydrates as glycogen, and in the Fat tissue we've stored Fats as Triglycerides, and in the Muscle we've stored Protein. So say a little time has gone by, and now the body needs to utilize its energy, but it can't just use Protein or glycogen or Triglycerides, it has to first break those nutrients down into more usable forms of energy. And the series of metabolic reactions that occur are known as the Post Absorptive State. In general, during the Absorptive State, we're building up and storing energy. In the Post Absorptive State, we're gonna be breaking down that, those molecules and releasing the energy. So, in general a lot of these reactions are just going to be going in the opposite direction, but not all of them, so let's go through them here. And once again, we're gonna start in the Liver. Now, in the Liver, glycogen is going to be broken down into glucose, and glucose can then be exported out of the Liver into the blood, and be used for energy all over the body. Now, the Amino Acids are actually still going to be taken up by the Liver. And just like during the Absorptive State, the Amino Acids are gonna be converted to Keto Acids and give off ammonia, which will produce Urea as a waste product. Now remember in the Absorptive State, the Keto Acids were turned into Fatty Acids to make Triglycerides. Well now in the Post Absorptive State, we're gonna use these directly to make glucose, and that glucose can be exported to be used by other parts of the body. But the Liver still requires energy of its own, so in part, these Keto Acids are still gonna be broken down into Acetyl CoA, to produce ATP. So what about glycerol and Fatty Acids? Remember in the Absorptive State, we were combining them into Triglycerides. But this is a storage nutrient, and in the Post Absorptive State we want to create more usable energy. So these are actually going to be also converted into glucose. Now there's one other important step in the Liver that's happening. Now these Fatty Acids can also undergo a second reaction, they can be broken down to form Ketones. Now, Ketones are an important metabolic intermediate, because they're one of the very few types of energy that can be used by the Brain. Now that we have a good idea of what's going on in the Liver in the Absorptive State, what's going on in Adipose? Well I mentioned earlier that Adipose is the storehouse of energy, and that energy is stored in the form of Triglycerides. Now, in the Post-Absorptive State, we want to use this energy, but we can't just use a Triglyceride, we have to break it down. So the Triglycerides are broken down, into glycerol, and Fatty Acids, and they can just be exported into the blood and are brought to the Liver to help make more glucose. Now, let's move on to Muscle. In Muscle, we have Proteins, and the Protein is gonna be broken down into its Amino Acids. And these Amino Acids are gonna be exported into the blood, and just like the glycerol and the Fatty Acids in Adipose tissue, these Amino Acids are also gonna make their way to the Liver, so that they can be converted to Alpha-keto Acids, and then converted into glucose, which is a more usable form of energy. But Muscles also contain some glycogen. And the glycogen is stored in Muscle, so that they'll have a little bit more direct access to energy. So in the Post Absorptive State, this glycogen is gonna be converted into glucose, and that glucose can be converted into Pyruvate, which can then go on to create Acetyl CoA, and produce energy through the electron transport chain. And this is all happening within the Muscle cell. But, I don't have it drawn in here, but these series of reactions right here, in order to produce this ATP for energy, it requires oxygen. But what happens if the Muscle cell is low on oxygen? Well luckily glucose can also be broken down into another product, and that's lactate. And when it's broken it down into lactate, we produce ATP, but we don't need the oxygen like we do during cellular respiration. Now you may be asking, "Well if you don't need "the oxygen, and you can still get the ATP, "why doesn't glucose always be broken down "into lactate and produce ATP?" And there's two reasons for this. This process here isn't as efficient, it doesn't produce as many molecules of ATP as would be produced if we went through cellular respiration. And also, this lactate is an acid, and it disturbs the pH-balance of the blood. So lastly, let's move back to the Brain. Now I said in the, during the Absorptive State, that the Brain just always uses energy. And that's true. Once again, we're just taking, the Brain is taking glucose from the blood, converting it into Pyruvate and going through cellular respiration to produce ATP. But also remember, the ketones from the Liver are also used by the Brain for energy in the Post Absorptive State. Now that we've gone through the Post Absorptive State and you see how the different tissues are breaking down and using energy, let's just bring back in the absorptive metabolic pathways, so you can get an idea of all the different types of metabolic reactions that are going on depending on whether your body is trying to store nutrients or utilize the nutrients.