Кто забирает глюкозу первым: печень, мышцы или мозг? GLUT и глюкокиназа

Explains how glucose uptake differs among liver, muscles, brain, and pancreas via GLUT transporters and kinases.

Key Takeaways

Glucose uptake depends on specific GLUT transporters and phosphorylation by kinases.
Brain and red blood cells require continuous glucose supply for survival.
Liver and muscle tissues balance glucose use for energy and storage.
Pancreatic beta cells link glucose metabolism to insulin secretion.
Insulin controls glucose uptake in muscle and fat by regulating GLUT4.

What the video covers

Glucose cannot pass cell membranes without specific protein transporters called GLUTs.
Glucose uptake occurs via facilitated diffusion through GLUT transporters without ATP consumption.
Once inside, glucose is phosphorylated by kinases (hexokinase or glucokinase) to glucose-6-phosphate to prevent it from leaving the cell.
Different tissues express different GLUT isoforms: brain and erythrocytes use GLUT1 and GLUT3, liver and pancreas use GLUT2, muscles and adipose tissue use GLUT4.
Brain and erythrocytes rely solely on glucose for energy and require constant glucose uptake regardless of blood glucose levels.
Liver and muscles can use glucose for energy or store it as glycogen, showing more flexible glucose metabolism.
Pancreatic beta cells use glucose metabolism to generate energy that triggers insulin secretion, regulating blood glucose.
GLUT and kinase enzyme kinetics, including Michaelis constants, determine glucose uptake efficiency in tissues.
Insulin regulates glucose uptake in muscle and adipose tissue by promoting GLUT4 insertion into the cell membrane.
Mutations in glucokinase can cause MODY diabetes by altering glucose sensing in pancreatic beta cells.

Chapters

Why can't glucose pass through the cell membrane on its own?

Glucose is water-soluble and the cell membrane is a phospholipid bilayer, so glucose requires specific protein transporters called GLUTs to enter cells.

What is the role of kinases in glucose metabolism inside cells?

Kinases phosphorylate glucose to glucose-6-phosphate, anchoring it inside the cell and enabling its use in metabolic pathways.

How does insulin affect glucose uptake in muscle and adipose tissue?

Insulin promotes the insertion of GLUT4 transporters into the membranes of muscle and fat cells, increasing glucose uptake.

Full Transcript — Download SRT & Markdown

Speaker A

Hello everyone, friends. You are on a channel dedicated to physiology and biochemistry. And today we will talk about how different cells in our tissues take up glucose, what they do with it, and what determines glucose uptake by different cells. Let's get started.

Speaker A

First, we will talk about why tissues take up glucose differently at the same blood glucose level. We will discuss the structure and function of transporters that move glucose across the cell membrane. We will also talk about the enzymes involved in the further metabolism of glucose. And, well, we will essentially break down some concepts of enzyme and transporter kinetics.

Speaker A

To begin with, let's talk about how glucose enters the cell at all and what the first action is that happens to it in a cell of absolutely any tissue.

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Let's start with the fact that glucose itself cannot pass through the cell membrane. Glucose is a water-soluble molecule. The cell membrane consists of a phospholipid bilayer, and there is a bit of a mismatch, because glucose cannot just simply enter the cell.

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That is precisely why glucose needs a special transporter to be transported into the cell. And for glucose in our body, special protein transporters have been created, which have the quite logical name GLUT. These transporters vary in their properties, and we will talk about that today.

Speaker A

But for yourself, you can remember that a GLUT molecule is a molecule that acts as a gateway for glucose, right? If there is no GLUT molecule, then, effectively, glucose will not enter the cell. Okay. What happens next?

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And, by the way, this path of glucose transport into the cell is considered facilitated diffusion.

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Why exactly is that? Because no ATP energy is consumed in this process, and glucose transport occurs with the help of this special transporter protein, right?

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So it is not quite simple diffusion, because there is a helper, and therefore it is called facilitated diffusion.

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And why can glucose pass specifically through this transporter? Well, because since the transporter itself consists of amino acids, it's a protein molecule, it actually provides a passage for this non-fat-soluble molecule through the cell membrane.

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What happens next? Next, glucose must enter into some chemical reactions. And in our body, there is a huge number of pathways through which we can use this glucose. These include glucose oxidation and energy production, glycogen synthesis, and so on.

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And the thing is, in order to start absolutely any metabolic pathway for using glucose in the cell, first, we need to ensure that the glucose does not leave the cell.

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Why does such a danger arise, so to speak, that glucose could leave the cell again? The thing is, GLUT molecules, that protein carrier, those gates, they are like doors that don't close completely, like in the subway or in walkways, they push both ways, right?

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Meaning, if we walk in one direction, we can open the door, and it opens just the same way in the other direction, so to speak. Man, I hope I explained that clearly.

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Well, basically, glucose can leave just as easily as it entered, and nothing will change. And so, the body needs to anchor this glucose inside the cell, so that it can definitely be used in some metabolic pathways.

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What actually happens? An enzyme works with glucose, attaching an anchor to it in the form of a phosphate residue. And we get glucose-6-phosphate.

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And this glucose-6-phosphate is a molecule that the cell can work with and use this glucose in any metabolic pathways. To do this, various kinases are at work. A kinase is, in principle, an enzyme that attaches a phosphate residue to a substrate.

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And in our body, again, there are different kinases that work with glucose in different ways. There is hexokinase, there is glucokinase.

Speaker A

And we will talk about the differences today. But the goal of this slide is to make it clear that for a cell to use glucose, we need to perform two actions. First, get the glucose into the cell using a GLUT molecule. Second, anchor this glucose and obtain glucose-6-phosphate.

Speaker A

And then this glucose-6-phosphate will be used. Let's move on.

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Now let's look at this big and at first glance very scary picture, but we will gradually break everything down. Here you see the brain, erythrocytes, liver, pancreas, and muscles. I would have liked to depict adipose tissue too, but, to be honest, I just forgot to draw it when I made this diagram.

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But the actions will all be similar to muscle tissue, so it's not a problem. So, what do we see? I depicted glucose as little candies. And notice that before entering absolutely any cell of any organ, glucose enters through the GLUT gates.

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And you see different GLUT molecules here in different tissues. In the brain, it is GLUT1. In erythrocytes, it is GLUT1 and GLUT3. Well, more precisely, in the brain it is also GLUT1 and GLUT3. In the liver, it is GLUT2. In the pancreas, it is GLUT2.

Speaker A

And in the muscles, it is GLUT4. But all of these are glucose transporters, those same gates through which glucose can enter. Okay. What happens next?

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Once a piece of candy or glucose has entered an organ, right, into a cell, an enzyme starts working on it, and we get glucose-6-phosphate. Yes, please follow along; you can see this on my diagram.

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And moving forward, after we have obtained glucose-6-phosphate, we actually start doing something with this glucose. So, what can we do with glucose? If we are talking about the brain and red blood cells, the main metabolic pathway that gets activated is glycolysis and the production of energy from glucose.

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If we talk about the liver, things are a bit different here, because glucose can be used by the liver both to produce energy, since hepatocytes also need it, and for glycogen synthesis. This is a special storage polysaccharide in which a large number of glucose molecules are kept.

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I have depicted it here as a jar filled with candies. If we talk about the pancreas, it is very important to note that the pancreas, naturally, 100% also needs to receive energy, and we will get energy from glucose in the pancreas.

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But it is also very important that specifically in the beta cells of the pancreas, the energy released after glucose oxidation will signal the beta cells to secrete insulin. And this is a very important point.

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That is, the production of energy by beta cells will trigger the release of insulin. And insulin, as you surely know, helps lower blood glucose levels. Therefore, we certainly shouldn't mess around too much here, because if we suddenly produce a large amount of energy in the beta cells when our blood glucose level is low, we could end up in hypoglycemia.

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Well, we will talk about that as well. As for the muscles, glucose entering the muscles is also mainly used for energy production. However, muscle glycogen synthesis can also occur in the muscles. But still, one way or another, the main pathway is energy production.

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Now, speaking of adipose tissue, which, similar to muscles, contains the GLUT4 molecule, glucose is also used in adipose tissue—excuse me, in adipose tissue—to produce energy.

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And in adipose tissue, we can also synthesize fats from glucose. So, notice that if we divide these organs into two camps, the red blood cells and the brain are quite simple.

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So, the only path, really, that they will use glucose for is obtaining energy. And without this glucose, these organs, in fact, will not be able to survive.

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Therefore, glucose must enter the brain and erythrocytes continuously, constantly, regardless of whether we have eaten or not. That is, the flow of glucose into these cells must be maintained on a constant, continuous basis, regardless of the blood glucose level we observe.

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If we are talking about the liver and muscles, the situation here is twofold. We can obtain energy from glucose, or we can store glucose as glycogen, keeping it in reserve, right?

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So, in a sense, the liver and muscles are organs that are, well, you know, very narcissistic and sometimes think only

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muscles and liver, there are two main ways to use glucose: obtaining energy and storing glycogen. If we are talking about adipose tissue, yes, it can also use glucose for different purposes.

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Obtaining energy and synthesizing fat, right? So, this is also, in a way, storing substrate for later use. Well, if we are talking about the pancreas, then, I repeat, it is for obtaining energy and as a signal to synthesize

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insulin. And now let's talk about how all these mentioned cells can take up glucose differently and use it in different ways, right? This is very important, this aspect of regulation in our body. Ah, okay. And we need to

Speaker A

introduce some rather complex concepts that you are bound to cover in biochemistry. They are extremely important. These are the Michaelis constant and Vmax. And what are these concepts even applied to? These concepts are applied to carrier proteins and enzymes. And surely you

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will touch upon this topic in enzyme kinetics. What is Vmax? It is the maximum rate of enzyme activity when all enzyme molecules are occupied, or carriers, if we are talking about a carrier. So, in essence, the maximum rate is the state of the enzyme where

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it is working at its maximum and can convert the maximum amount of substrate to produce the maximum amount of product. In reality, the rate of enzyme activity is actually very, very difficult to evaluate. And it is mainly evaluated either by the decrease in the

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amount of substrate or by the increase in the amount of product. That is, the more substrate we process and the more product we obtain per unit of time, the higher the rate. Well, I think the concept here is quite logical. When we

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talk about the Michaelis constant, it is a rather complex concept. Please note that the Michaelis constant does not reflect the rate, but the concentration of glucose—in our case, the substrate—at which the rate of the enzyme or transporter is half of

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its maximum. It sounds quite complicated. Let's use an analogy. Suppose I am some kind of enzyme, and I really love sweets. Actually, that's true, but that's not the point. So, let's imagine two people, which represent two different enzymes. One of

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them is me, who loves sweets very much. The second enzyme is the type that says : "Well, I don't really like sweets, and I will only eat them if, I don't know, there's a huge amount of them and

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no other food, then maybe I'll eat a cookie." If we take the first enzyme, specifically me, who loves sweets very much, I will start consuming sweets as soon as they appear in my house. If even one cookie flies into my house, it

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will be consumed. That means my Michaelis constant will be very low. The concentration of cookies at which the rate of my eating them equals half the maximum will be very low. Perhaps you are very confused by this concept

Speaker A

of "half the maximum"; you might ask why not just use Vmax, but for the Michaelis constant, exactly half the maximum velocity is used. But what is the main point? The point is that the Michaelis constant is an indicator that

Speaker A

reflects the affinity. of an enzyme or transporter for a substrate. If my Michaelis constant is very low, it means I will consume cookies as soon as they appear in my house. Even if it's just one cookie, I'll eat it right away

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. If there is an enzyme sitting next to me that doesn't really like cookies, the consumption of these cookies by this non-sweet-loving enzyme will only begin when there are a great many of them. The concentration of glucose will

Speaker A

be very, very high. And this will indicate a high Michaelis constant. And a high Michaelis constant indicates a sort of low affinity of the enzyme or transporter for the substrate. For now, just understand these concepts; later, we will break down which organs have

Speaker A

which Michaelis constants. So, yes, let's look at the graph. What do we see on the graph? We see a representation of a low Michaelis constant and a high Michaelis constant. Here in blue, yes, we can directly observe that at very

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low glucose concentrations the Michaelis constant, the rate, no, not the rate, to be precise, the Michaelis constant, I misspoke. Let's wipe, let's wipe that moment. Look at the graph, at the blue curve. Ah, yes. So we see that

Speaker A

the Michaelis constant of this blue enzyme is very low, meaning half the maximum velocity, yes, the segment where the Michaelis constant is marked, is reached at the lowest possible glucose concentration. Meaning this is an enzyme that loves glucose very much

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and possesses a very high affinity for this substrate. And right next to it, we see an orange dashed graph where the Michaelis constant is quite high. That is, for this enzyme, half the maximum velocity will develop only when there

Speaker A

is a lot, a lot of glucose, right? Well , in particular, this is 10 mmol/L. In this way, yes. Therefore, when we see such graphs, what can we say? That the affinity of an enzyme that has a low

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Michaelis constant for its substrate is very high. And the affinity of an enzyme that has a high Michaelis constant for its substrate, on the contrary, is quite low. Okay, let's move on. And now let's get to the most

Speaker A

interesting part. Let's look at why we were actually delving into this enzyme kinetics in the first place. Let's start with the liver. I remind you that the liver is a dual-purpose organ. It can both obtain energy from glucose and

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store this glucose for later use. That is, theoretically, if we give the liver glucose, it can quickly oxidize some of it and store some of it away, so to speak. And doing this is maximally disadvantageous when we already have a

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low concentration of glucose in the blood. For example, we wake up in the morning on an empty stomach, haven't eaten anything yet, and our blood glucose level is within the normal range. And imagine if at this moment the liver was like: "Hmm, I think I'll

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synthesize some glycogen, take all the glucose out of the blood so my human falls into hypoglycemia, and store this glucose for later." Well, we wouldn't have survived, obviously. So, how has the organism actually, well, not adapted to this, but how is it set up?

Speaker A

The GLUT2 transporter works in the liver. So we will now always evaluate the enzyme kinetics of the transporter through which glucose enters the cell, through which glucose enters the cell, and the kinetics of the enzyme that anchors this glucose. Yes, remember we

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looked at the fact that we have two steps: letting glucose into the cell and phosphorylating it so that it gets anchored. And if we look at the Michaelis constants for GLUT2 and the enzyme glucokinase that works in the

Speaker A

liver, we will see they are quite high. Note that the Michaelis constant for GLUT2 ranges from 17 to 20 mmol/L. This means the liver only begins to reach half of its maximum glucose uptake capacity when we enter hyperglycemia.

Speaker A

And this makes sense, because the liver is an organ that can both generate energy and store glucose for later use.

Speaker A

Yes. And, of course, the body thinks: " Hmm, since you can store glucose as a reserve and synthesize glycogen from it , it means no matter how much I give you, it will never be enough." You can synthesize a huge amount of this

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glycogen there. And, accordingly, it is logical that the liver starts to absorb and phosphorylate glucose only when there is a lot of it. For example, after a meal, when we reach a certain level of postprandial hyperglycemia. Of course, this does not at all mean that

Speaker A

at lower blood glucose values, say 10 or 12, it does not work. No, it works, but slowly. Yes, because usually the level of postprandial hyperglycemia, that is, the rise in glucose after a meal, can be around 8–10 while the

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body begins to utilize that glucose, so to speak. Therefore, do not look at the fact that the Michaelis constants are between 17 and 20. It simply means that the glucose concentration at which GLUT2 develops half of its maximum

Speaker A

velocity is 17–20. Accordingly, if the glucose level is lower, GLUT2 works slower. And I will emphasize once again , this is logical because the liver can store glucose as a reserve. That is why we do not allow the liver and the

Speaker A

liver's GLUT2 to capture glucose constantly, otherwise we would simply fall into a hypoglycemic coma if we woke up in the morning and hadn't eaten , and the liver decided: "I think I'll grab all the glucose from the blood." I

Speaker A

hope that's clear. And the next enzyme, the next step that happens in the liver , is phosphorylation, or anchoring the glucose so that we can use it for something at all. And here, the enzyme glucokinase is at work. The enzyme

Speaker A

glucokinase works in the liver and in the pancreas. And glucokinase also has a relatively high Michaelis constant of up to 7–8 mmol/L. This means, once again, half of the maximum velocity of this enzyme is reached when the blood

Speaker A

glucose level is 7–8 mmol/L. Again, this does not mean it doesn't work at lower concentrations, but still. Once again, why is this done? So that the enzyme uses glucose inside hepatocytes only when there is a relatively high amount of it in the blood, right? That

Speaker A

is, essentially, when we wake up in the morning on an empty stomach, GLUT2 will practically not work. And neither will glucokinase. Well, not that it won't work at all, but their reaction rate will be as low as possible so that we

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don't fall into hypoglycemia. And here on the graph, you can see the Michaelis constants for GLUT2 and glucokinase.

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Yes, note that they are quite high. Okay, let's move on and look at the pancreas. Specifically, we are interested in the pancreatic beta cell, which works, uh, which produces insulin . In the pancreas, if you open textbooks, they mostly state that

Speaker A

pancreatic cells, the beta cells, function precisely by using GLUT2. Let's stick with this strategy for now, and I will add a small correction later regarding how it actually works in humans. Essentially, the mechanism for processing glucose in the pancreas is

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very similar to what happens in the liver, right? That is, conditionally we have GLUT2, and among the enzymes we have glucokinase, both of which have relatively high Michaelis constants.

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Again, why is this done? This is done so that the beta cell can receive a large amount of energy and trigger insulin production only when the glycemic level is relatively high. Yes, if the beta cell were to receive

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glucose, let's say, with the help of other transporters that work at lower glucose concentrations, then we would again drift into a state of hypoglycemia. Therefore, for glucokinase, the Michaelis constant will be relatively high in comparison to other enzymes that we will analyze a

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little later. And here I would immediately like to tell you an interesting thing. This is a connection to pathophysiology, because we have two conditions in which the function of glucokinase is somewhat impaired. Yes, it happens that due to various genetic

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characteristics, the enzyme may not work the same way as in a healthy person. And now, let's think about this together. What do you think a decrease in the Michaelis constant of the glucokinase enzyme would lead to? Stop and think, okay? That is, when we lower

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the Michaelis constant, it means that the enzyme will reach half of its maximum reaction velocity at a lower glucose concentration. Now answer the question: what does this lead to—the development of hyperglycemia or hypoglycemia? Think about it. The correct answer is hypoglycemia, right?

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That is, if for some reason—primarily genetic—glucokinase has a lower Michaelis constant, it means that it will reach half of its maximum velocity at low glucose concentrations. And this will lead to the fact that energy will be synthesized inside the beta cell,

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insulin will be produced, and we will fall into hypoglycemia. And hyperinsulinism may be linked to this very condition, right? That is, this is a specific pathological state where, due to glucokinase being highly reactive and having a low Michaelis

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constant, a large amount of insulin is produced, and, consequently, the person develops hypoglycemia. Such a condition does exist, yes, as a separate pathology. Now for the opposite situation, when glucokinase, conversely , has a higher Michaelis constant. Yes, let's think about this again. If it is

Speaker A

a higher Michaelis constant, it means glucokinase will reach half of its maximum velocity at higher glucose levels. And what will this lead to? The development of hypoglycemia or hyperglycemia? Well, the correct answer here is: hyperglycemia. And it is

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precisely this type of glucokinase mutation, where it has a higher Michaelis constant, that is associated with certain types of genetically determined diabetes, specifically MODY diabetes. And it is characteristic of such people that they are in a state of

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hyperglycemia, unlike a healthy person. I hope I explained that clearly, yes? This is precisely the topic in biochemistry that has a clear parallel with various clinical manifestations.

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Okay, we've sorted out the beta cell. Moving on. Let's now talk about muscles and fat. Things are quite interesting here because in muscles and fat, we have the GLUT transporter working. What is its peculiarity? Its peculiarity is that in a resting state, this

Speaker A

transporter is not in the cell membrane , but inside vesicles. Please look, I drew this specifically in the muscles, right? That is, the cell has a special vesicle which contains these GLUT4 transporters. In certain situations— we will discuss which situations now—

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when something affects the cell, these vesicles embed into the membrane, GLUT4 embeds into the membrane, and glucose enters the cell. And then glucose is processed by the enzyme hexokinase. Not glucokinase, but specifically hexokinase. I will tell you about the

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differences now. And why is that? The thing is, muscles and fat, yes, of course, they must receive glucose to produce energy, but muscles and fat are also organs that can store this glucose either as glycogen, if we are talking

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about muscle tissue, or as triacylglycerols, if we are talking about fat. But actually, by the way, triacylglycerols can also be synthesized in muscles. Well, all right . So, these are also organs that know how to store glucose for future use.

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Therefore, how did nature, or evolution , come up with this? Evolution designed it so that GLUTs, these gateways that let glucose into the cell, only appear in the membrane when they are needed.

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If we take a muscle, when is that needed? It is needed at the moment of muscle contraction. That is exactly why , during muscle contraction, a pathway inside the myocyte is activated that transports GLUT4 molecules to the membrane. That is precisely why muscles

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are such good glucose absorbers. The second factor that, let's say, inserts GLUT4 molecules into the membrane is insulin. By binding to muscle cells and fat cells, insulin also activates the insertion of GLUT4 molecules into the membrane so that the cell can absorb

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glucose. And then, the phosphorylation of this glucose takes place. In both muscle and adipose tissue, the enzyme hexokinase is at work. Hexokinase is an enzyme that has a fairly low Michaelis constant, working at a very low glucose concentration, reaching half its

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maximum velocity. There we go. But nevertheless, if we take GLUT4 specifically, the Michaelis constant for GLUT4 is about 4-5 mmol/L. Meaning it is not as high as, for example, the GLUT2 molecule, where the Michaelis constant is around 17 mmol/L. So that

Speaker A

is how the story goes here. In other words, the Michaelis constant for GLUT4 is somewhat lower than it is for the liver. And in both muscle and adipose tissue, the enzyme hexokinase is at work, which also has a fairly low

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Michaelis constant. This, by the way, explains the fact that people suffering from diabetes (where there is either absolute or relative insulin deficiency ) find that physical activity helps them lower blood glucose levels, precisely because muscle contractions activate the insertion of GLUT4

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molecules into the cell membrane. Okay, moving on. Now let's talk about the brain and red blood cells. We have already mentioned that the brain and red blood cells are organs that absolutely need glucose constantly, always, in any state—on an empty

Speaker A

stomach, after lunch, it doesn't matter at all. Therefore, in brain cells and red blood cells, GLUT1 and GLUT3 transporters are at work. And these are transporters that have a very low Michaelis constant. These are the very transporters that have a high affinity

Speaker A

for glucose molecules and begin transporting them immediately, regardless of their concentration. Right. And if we look at the enzymes that work in the brain and red blood cells, it is the enzyme hexokinase, which also has a low Michaelis constant

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. And why is it designed that way? Yes, it's designed this way because the brain and red blood cells are cells that do not store glucose for later.

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They use it here and now to sustain their life functions. That is why we need to ensure a continuous supply and metabolism of glucose. Yes. So, we don't bother with raising the Michaelis constant here, which would make cells

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absorb glucose only when there is a lot of it. The situation here is the opposite. We need everything to always work at maximum capacity. Even on an empty stomach, even when you haven't eaten all day and your glucose level is

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within the normal range or closer to the lower limit. There. Actually, this is the main difference, yes, between the brain, red blood cells, the liver, and the pancreas, yes. I will repeat once again: if we are talking about the

Speaker A

liver and the pancreas, glucose uptake by these cells will mainly occur only when there is something to store this glucose from, yes, and there is a need to produce insulin at higher values.

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The brain and red blood cells will absorb and metabolize glucose even at its minimum concentrations. And I didn't mention an important correction regarding the pancreas. I completely forgot. If we look at textbook data, Severin's in particular, he writes that

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the pancreas has GLUT2 molecules in its membrane. But according to modern research data, conducted directly on humans, the main transporter in the pancreas is actually GLUT1, right?

Speaker A

Therefore, when answering on an exam, pay attention to GLUT2, but you can also note that you are aware of modern data. But this does not spoil the picture in any way, because even if we assume that GLUT1 transporters are

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present in the pancreas, okay, they will absorb glucose even at low concentrations, but due to the fact that glucokinase itself has a relatively high Michaelis constant, right? That is, it will metabolize glucose only when its concentration reaches, well, quite high values. There

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. I hope I explained it clearly. Oh, and let's look at this comparative graph of Michaelis constants for GLUT1, GLUT3, GLUT4, and GLUT2. Yes. And what do we see? GLUT1 and GLUT3 have the highest Michaelis constants. This means

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that they will reach half of their maximum operating speed at low glucose concentrations. And this is justified, because these transporters are found in red blood cells, in brain cells, and in placenta cells, by the way. And these are the tissues that need a constant,

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continuous supply of glucose. And they use it only to obtain energy. If we look at the GLUT4 molecule, which is depicted in green, the Michaelis constant is somewhat lower. And GLUT4 is located in adipose tissue and in muscle cells, right? Ah, and here the

Speaker A

Michaelis constant is lower because, once again, um, yes, it's lower because these are cells that can store glucose for later. That's why we only provide glucose when there is a certain surplus of it, so they don't take all the

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glucose out of the bloodstream. And the highest Michaelis constant is found in the GLUT2 molecule, which is located in the liver and, according to older data, in the pancreas. And again, biologically, this is to ensure that we allow the liver and pancreas to

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metabolize glucose only when there is plenty of it, so that we don't drift into some kind of hypoglycemia. There.

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Okay. Well, here are some numbers. If we look at the liver, the GLUT2 molecule is at work. The Michaelis constant is quite high, 17-20. The enzyme glucokinase also has a relatively high Michaelis constant. If we are talking about a pancreatic beta

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cell, the textbook says it's GLUT2, but modern data suggests it's actually GLUT1. The Michaelis constant for GLUT1 is very low, but because glucokinase with a relatively high Michaelis constant is at work, the beta cells will still metabolize glucose only at,

Speaker A

well, let's say, higher levels. But again, if you are answering an exam, stick to the main line interpreted in textbooks, but you can show off your knowledge by mentioning that you are aware of the new data. If we talk about

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muscles and fat, GLUT4, the Michaelis constant is around five, which is already, well, a borderline value compared to GLUT2 and GLUT1. And hexokinase is at work in muscles and fat. This is an enzyme with a fairly low Michaelis constant. Well, if we

Speaker A

talk about the brain and erythrocytes, GLUT1 and GLUT3 transporters are at work with a very low Michaelis constant because glucose is vitally necessary at all times. And the enzyme hexokinase also has a fairly low Michaelis constant. Therefore, if we compare two

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main states, for example, fasting and after a meal, who takes the glucose? When fasting, it is mainly the brain and erythrocytes. Why? Today we figured out why. Because the Michaelis constant for GLUT1 and GLUT3 molecules and for hexokinase enzymes is quite low. It is

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precisely this that ensures a constant influx of glucose into these cells. The brain and erythrocytes will always be in first place, both when fasting and after a meal. But note that after a meal, the liver actively joins in due

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to glucokinase and the activity of GLUT2 molecules, which transport glucose into the cell. And also muscles and fat, which are somewhere, somewhere in the middle, will also receive glucose only if insulin acts on them or , in the case of muscles, if a muscle

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contraction occurs. That's such an interesting story. And we have analyzed two points related to glucokinase pathology. These are MODY diabetes and congenital hyperinsulinism. I won't repeat myself, okay? The difference here lies in what mutation occurred in the glucokinase, making it have a

Speaker A

higher Michaelis constant or, conversely, a lower Michaelis constant. There is also a pathological condition known as GLUT1 deficiency syndrome.

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Honestly, I don't remember the eponym for this syndrome. But what is the essence of it? In the brain, GLUT1 is extremely important because it is a glucose transporter. And in a state where there is not enough GLUT1, the

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brain accordingly does not receive a sufficient amount of glucose. This can affect development and provoke the development of various seizures, epilepsy, and so on. The main manifestation is, of course, intractable epilepsy, intractable seizure attacks. In this case, the

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brain works mainly on ketone bodies, because there is no way to oxidize glucose normally, since it simply cannot enter the cell. And yes, for these conditions, specific keto diet protocols are even used, but that is a completely different story. So, let's

Speaker A

summarize. Glucose uptake by tissue is determined by three things. These are the Michaelis constant of the transporter, the Michaelis constant of the enzyme, and in some cases, insulin.

Speaker A

If we are talking about the brain and red blood cells, the transporters and enzymes have a very low Michaelis constant and work quite quickly. And if we are talking about organs like the pancreas and liver, because glucokinase has a lower—or rather, a higher—

Speaker A

Michaelis constant, and because the GLUT molecule has a higher Michaelis constant, glucose uptake by these tissues will occur as the blood glucose concentration rises. Now, if we are talking about muscle tissue and adipose tissue, everything here is tied either

Speaker A

to the action of insulin or to the action of muscle contraction. Friends, I hope this video was interesting for you and will help you understand biochemistry and answer questions on the exam. Be sure to subscribe and see you in the next video.

Topics:glucose uptakeGLUT transportersglucokinasehexokinaseglucose metabolisminsulin secretionliver glucosemuscle glucosebrain glucosefacilitated diffusion

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