01.04 Carbohydrate Metabolism

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Outline

Overview

  1. Big Picture Overview
    1. This is an overview to help you see how the main carbohydrate metabolic pathways relate to one another
  2. Carbohydrates are sugars
    1. Monosaccharides: glucose & fructose are different in how they are metabolized
    2. Disaccharides: sucrose & lactose are basically glucose or fructose, so the metabolism of these two sugars is what we will focus on
    3. Glucose is the most important of them all
      1. Used by cells throughout the body
      2. Blood levels kept within tight range around 100 mg/dL
  3. Glucose Pathways
    1. The pentose phosphate pathway creates NADPH & ribose for DNA & RNA
    2. Glycogenesis & glycogenolysis are glycogen synthesis & breakdown, respectively and are how excess glucose is stored & released when blood glucose levels get low
    3. Gluconeogenesis is “glucose-new-make” and is how glucose is made from small molecules like lactate, certain amino acids & the glycerol backbone of triglycerides (stored fats)
    4. Gycolysis
      1. The 6-carbon glucose molecule is split into two 3-carbon molecules: DHAP & GAP
      2. 2 ATPs are invested, 4 ATPs are produced by glycolysis, for a net synthesis of 2 ATPs
      3. Pyruvate is converted to acetylCoA, an important “two-carbon chunk”
      4. AcetylCoA can enter Krebs/ETC to create many more ATPs or it can be used to synthesize fatty acids which are usually stored in fat cells
      5. Pyruvate can also be used to make ATP & lactate in working muscles
      6. The lactate can be converted back into pyruvate, and then through a process similar to the reverse of glycolysis, new glucose molecules can be made (i.e. gluconeogenesis)
  4. Fructose
    1. Fructose is primarily processed by the liver, like alcohol
    2. It can be used to replenish glycogen stores
    3. If energy is not needed and glycogen stores are full (like after a meal) the fructose gets converted to fat.
    4. If this happens to much, the fat can accumulate on the liver and cause fatty liver disease.
  5. In summary
    1. Glucose is central to carbohydrate metabolism
    2. The pentose phosphate pathway uses glucose to make NADPH & ribose
    3. Glucose is stored as glycogen and is released when blood levels get low
    4. Glucose is made via gluconeogenesis from small non-carbohydrate molecules
    5. Glucose is “split” and then “burned” via glycolysis, the Kreb’s cycle & the ETC to make cellular energy, ATP
    6. Fructose is metabolized by the liver
    7. Excess glucose & fructose are converted to fatty acids via acetylCoA

Transcript

Hey there. What we’re going to talk about today is an overview of carbohydrate metabolism. This one is a biggie. We’re going to focus on glucose and glycogen. We’ll talk about gluconeogenesis and fructose and actually quite a bit more. The focus is going to be more, I would say, wordy than it is chemistry. So we’re just going to try to mostly familiarize you with the different words surrounding carbohydrate metabolism. First we’re going to start with a refresher on carbohydrates and then we’ll go into glucose metabolism, and that’s really where a lot of complexity is. And then we’ll touch on fructose metabolism at the end.

Here’s a reminder…these are monosaccharides. They have single ring structures. Glucose and fructose are two of the most common examples. And what you’ll notice here is that with glucose, we’ve got C-6, H-12, O-6, and fructose has the exact same formula, C-6, H-12, O-6. They’ve got the same carbons, hydrogens, oxygens, but they’ve got different shapes…they’ve got things in different places. You see here, there’s an OH coming down below and then there’s also one up above. Whereas in this case–glucose–there is no CH2OH here, just the OH down below. That’s what allows it to be a six membered ring instead of five. Both of them do have this CH2OH up here. So while they have the same formula, they behave very, very differently in our bodies.

Glucose is incredibly important. It is so important that our bodies make it. There are cells in our body that have an absolute requirement for glucose. And so this guy here, you know, super key, super important. Fructose, we just love fructose because it’s sweet. That’s why we like it. And it is in fruit and it is natural, but it doesn’t get processed in the same way that glucose does. We’ll talk about that at the end of the presentation here.

Now I want to point out something let’s look, count these carbons up. So this is what we call the 1- carbon. So carbon-1, carbon-2, carbon-3, carbon-4, carbon-5, carbon-6. Okay. So here at carbon-4, notice that this OH is going down; we have this down direction for it. Now we’re going to turn and look at some disaccharides. So these are sugars that have two rings in them, two rings stuck together. Lactose is a galactose and a glucose stuck together. This has that same shape as the glucose, right? Carbon-1, carbon-2, carbon-3, carbon-4, carbon-5, carbon-6. But notice how, in this case here at carbon for the OH goes up. That’s the only difference between a galactose and glucose. There are enzymes called epimerase that will come around and change this. So this (galactose) is the epimer of glucose and an epimerase will change this direction and put it downward. That happens very readily, so for all intents and purposes, the galactose is just a glucose. So lactose just gets processed like glucose.

Now the story is different over here with sucrose. This is table sugar, right? Table sugar is sucrose, and it is a glucose bound to a fructose. That’s why table sugar is so sweet is because we have that fructose piece in it. And it ends up that pretty much anything that’s natural that’s sweet–with probably the only exception would being like Stevia sweetened stuff–but just anything in nature that has to do with fruit or honey or maple syrup, even high fructose corn syrup, it’s going to be some combination of glucose and fructose. Sometimes they’re stuck together like this. Sometimes they’re just apart, i.e. a glucose and fructose floating around. But there’s always some combination of glucose and fructose that makes things sweet. There are enzymes that will come through and cleave this bond really easily. So the fact that they’re glued together, isn’t really a big deal.

Let’s take a look at glucose metabolism. What I’ve drawn here…we’ve got these six blobs. Those stand for the six carbons of glucose and glucose can go in so many different directions, as seen on the next slide. We’ll look at glycolysis and I have a lot more information to share with you about that. But let’s look over here…pentose phosphate pathway, PPP. What this guy does is it is a way to make ribose from the glucose. If you remember, ribose look like this…a little guy like that, and he’s got an OH that comes off the top. There it’s five carbons. So one, two, three, four, five carbons on it. And that’s what goes into DNA and RNA. The missing carbon, right? We started with six here and we went down to five. That’s because there’s a CO2 that gets made over here. And then the other thing that’s important about the pentose phosphate pathway is this is how we get NADPH. Remember this H–it gets hooked onto things like, in particular, taking acetylCoA, adding H’s to it will help build up a fatty acid. It’s called reductive biosynthesis, and I’ve touched on that in some other videos. It’s a good thing to know, and it is a little bit different than NADH, which we’ll talk about a little bit later in this video. Okay. So that’s, pentose phosphate pathway.

Let’s come over this way. Glycogenesis. This is how we make glycogen. Glycogen is a bunch of glucose’s all linked together, and it gets to a branch point and then the glucoses continue on like that. And this is the way we store glucose. As we get all the way out to the ends here, we’ve got these little glucose molecules, and there’s lots and lots of these ends that are in the glycogen. They can get eaten up easily…little enzymes will come and eat back all of those little glucose’s that are there. That’s what gives us fast fuel. Glycogen is the way we store glucose and we do it in our livers and in our muscles. And it’s for fast energy.

Now, if we look at the other side…it’s called glycogenolysis. I want you to be familiar with these two words: Genesis–you can kind of think of the Bible Book of Genesis…making of the earth. That would be “make”. That’s the idea of make, but over here, ‘olysis’ or just ‘lysis’, that means split. Split is what ‘lysis’ means. So if we’re going to split all those guys off that’s glycogenolysis. If we’re going to make it, that that’s like genesis.

And then down here in this corner–oh, I love this one so much. This is gluconeogenesis: glucose, neo means new, and then here we are with make. So this is how we make glucose and we can make it from lactate and we can make it from certain amino acids. We can make it from glycerol. You may not be too familiar with where these things come from. The amino acids would come from things that we eat; we can also make certain amino acids. Lactate would come from doing anaerobic metabolism off of the glucose, and so that’s another direction that we could go in. We’ll talk about that later.

Here we would go from the pyruvate we have over here that can turn into lactate, and that’s another fast way of getting energy glycerol. If we think about a triglycerol, also called a triglyceride…the backbone here is three carbons, one, two, three. So the glycerol backbone, with fatty acid chains coming off of it. Two of these three carbon molecules can come together to make a six carbon molecule, ta da, you’ve got glucose. So these are all ways that you can make new glucose.

Let’s look at glycolysis and I wrote it this way, glyco-lysis. This means glucose split. Here’s our six carbon sugar, the six carbon glucose, the key part. I’m not going into chemical detail on this–we could do that in another video, or you can go look in your biochemistry textbook. There’s really complex chemistry that needs to take place here, and I’m not showing that. The main split thing that happens, this is dihydroxyacetone phosphate (DHAP) over here and this is glyceraldehyde phosphate (GAP). The six carbons get converted into two, three carbon chunks. And it’s the GAP side that keeps going on down to create pyruvate. Now this part up here requires ATP. So two ATPs need to come into this, and four ATPs come out of this. In addition, an NAD is going to come out of this. This means that the net ATP is going to be two ATP. Since you had to invest two here, but you got four out in the end. That’s how we ended up with a net of two.

What happens to that pyruvate once it gets made? So many different directions that it can go in: it can be used to create acetylCoA, which is something that we talk about in the Krebs cycle video. And then that can be used to create CO2 and ATP. That’s basically the combustion reaction of taking that glucose that you ate and burning it and making CO2 and water out of it. And in the process generating energy. If your body doesn’t need energy, the glucose can get converted to this acetylCoA, and then it can get built up, using that NADPH, into fatty acids. Those fatty acids can go on to do a variety of things, but one of which is to just get stored as fat. That’s how eating sugar or glucose can increase your fat levels…because anything that you don’t need for energy will just get stored as fat.

Similarly, I mentioned how pyruvate can get converted to lactate. This happens in muscles when muscles are working really hard, then that process happens and generates some ATP. And similarly, the pyruvate can go on to create more glucose. So the lactate could get converted back to pyruvate. And then that actually goes into gluconeogenesis.

Let’s just touch for a moment on fructose metabolism. Unlike glucose, fructose is primarily metabolized in the liver. Glucose is metabolized by cells all throughout the body, but that is not the case for fructose. Interesting thing, fructose. It’s almost like it’s metabolized more like alcohol would be, like ethanol. And that is, it gets processed by the liver and it can get converted into glycogen. The fructose gets converted into glucose, and then it can get converted into glycogen. If you’ve been out exercising a lot and your glycogen stores are low, then you go have a Gatorade, that’s got sucrose in it (that is fructose), then you’re going to replenish your glycogen stores. That’s a healthy direction. But one of the problems that we have is that when we eat fructose, and again, this fructose is attached to glucose in the sugar that we eat…let’s say you had a big meal and then you had some dessert. At that point, your glycogen stores are full. Your body doesn’t need the energy. So that dessert just goes straight into fat stores. A problem for people these days…starting to be more and more of a problem…is that that this fat often doesn’t leave the liver and it ends up staying there and it causes non alcoholic fatty liver disease. NAFLD is what that’s called, and it’s not good because it ends up with this fat that accumulates around on the liver and that leads to metabolic syndrome. Some serious stuff that’s associated with fructose metabolism.

Let’s summarize. We covered a lot of things here. We’ve got glucose…pentose phosphate pathway was one possibility for it. Energy is another direction it could go. Or it gets stored as fat. Or it can be stored in glycogen. So glycogen…glycogenesis is about the creation of glycogen. Glycogenolysis is about the breakdown in the glycogen. And then gluconeogenesis…that’s the one where the body’s going to make new glucose; and it’s going to do that from lactate, certain amino acids, and that glycerol backbone from triglycerides. And then lastly, fructose…different from glucose because it’s primarily metabolized by the liver, but it too can also get turned into fat and lead to problems. Alright, here we are. We love you guys! Go out and be your best self today and as always happy nursing!