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01.11 Regulation and Integration

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Overview

 

  1. Overview of Regulation and Integration
    1. Key metabolic pathways
    2. Key organs that carry out different metabolic pathways
    3. Hormones as metabolic regulators
  2. Five key metabolic pathways, focusing on glucose & fat metabolism
    1. Glycolysis
    2. Gluconeogenesis
    3. Glycogen synthesis & breakdown
    4. Fatty acid breakdown & synthesis
    5. Kreb’s Cycle / Electron Transport Chain (ETC) / Oxidative Phosphorylation
  3. Five organs that carry out various metabolic pathways
    1. The liver is the “master of metabolism”
      1. Glycolysis
      2. Gluconeogenesis
      3. Glycogen synthesis & breakdown
      4. Fatty acid breakdown & synthesis & triglyceride formation
      5. Ketone body synthesis
      6. Conversion of lactate back to glucose
      7. Amino acid metabolism
      8. Toxin elimination, e.g. urea
    2. The brain is a big energy user
      1. Glucose –> AcetylCoA
      2. Ketones –> AcetylCoA
    3. Muscles use multiple fuel sources & create lactate
      1. Glucose (from blood stream & glycogen)
      2. Ketones
      3. Fatty acids
      4. Lactate goes to the liver to get “recycled”
      5. Breaking down muscle protein is a last resort
    4. Adipose tissue (aka fat cells) serve as storage
      1. Glucose –> AcetylCoA
      2. AcetylCoA –> Fatty acids
      3. Fatty acids –> Triglycerides = FAT
    5. The kidneys are somewhat similiar to the liver
      1. Amino acid metabolism
      2. Toxin elimination, e.g. urea
      3. Ion balance
  4. Hormones are regulators
    1. Molecular “messengers” that tell the body what to do
      1. Protein-based, e.g. insulin
      2. Small organic molecule, e.g. adrenaline (aka epinephrine)
    2. Insulin is the main storage hormone–it stores energy
      1. Increases glycogen synthesis (glycogenesis)
      2. Decreases glycogen breakdown (glycogenolysis)
      3. Increases fatty acid synthesis
      4. Decreases fatty acid breakdown (beta-oxidation)
    3. Adrenaline is the fight or flight hormone–it creates energy
      1. Decreases glycogen synthesis (glycogenesis)
      2. Increases glycogen breakdown (glycogenolysis)
      3. Decreases fatty acid synthesis
      4. Increases fatty acid breakdown (beta-oxidation)
  5. Summary
    1. Five key metabolic pathways focus on glucose & fat breakdown & storage
    2. Five key organs carry out different metabolic pathways
      1. The liver is the “master of metabolism”
    3. Hormones
      1. Insulin = storage hormone; storing glucose & fatty acids for use at a later time
      2. Adrenaline = fight or flight hormone; releasing glucose & fatty acids to be burned for energy

Video Transcript

So today we’re going to talk about the regulation and integration of metabolic pathways. And this is a really big picture perspective here. I’m going to actually kind of switch the order…we’ll first talk more about integration and then at the end, we’ll talk about regulation. Key metabolic pathways, I mean, all of your metabolic pathways are important. So I’m going to try and break it down to what I would consider the key ones. But of course, I’m really just giving you just a small snapshot of all the metabolic pathways. We’re also going to talk about the most important organs for carrying out these different metabolic pathways. And in the end, I’m going to give you two examples of hormones that help to regulate these processes.

Key metabolic pathways: Glycolysis–that’s the splitting of glucose; gluconeogenesis–that is going to be the making of new glucose, glycogen–is how we store glucose…so we synthesize glycogen and that’s storing glucose or we can break down that glycogen in order to generate some little glucose molecules that we can use for quick energy. And similarly, there can be a fatty acid breakdown and also fatty acid synthesis. You’ll see that these are broken down into the glucose category and the fat category: these are the two main ways that we get energy, and that’s why they’re so important. And then how we get energy is that these both can generate acetyl-CoA, and that’s what enters into the Krebs cycle…the carbons come out as carbon dioxide. And we get some high energy molecules from the Krebs cycle…those high energy molecules deliver electrons to the electron transport chain, and in turn, we’re able to generate some ATP through that process. This is what I would consider the key pathways, but gosh, there’s so much more to it. Like for example, lactate is something that can come from glucose metabolism. Also, things like ketones can come from fat metabolism. Both of those are really important. And you’ll notice I also have kind of skipped out on talking about any amino acid pathways….amino acids are also so important, but, one of the sort of main things to think about here is when you actually metabolize amino acids, you make ammonia and the ammonia–we need to get rid of that. That’s toxic and we can create urea. I bring these up because I’m going to touch on them as we go through some of the different pathways.

These are key organs–and of course, all your organs are important–but I would say these are the key metabolic ones. Pretty interesting. You know, your brain is only about 2% of your body, but it uses 20% of the energy. So massive energy use in our brains. The liver–this guy is going to be that master of metabolism. And we’ll talk about why that is. Muscles also super important–they store glycogen but they also use lots of energy, and obviously they’re the things that we need to get us around in the world. And adipose tissue–so this is about storage, and so we’ll talk about that. How we store calories is in fat in our adipose tissue. And then lastly, I’m going to put kidneys in here because kidneys are also super important.

What I’ve done is I’ve tried to meld together the different pathways and put them into categories here. So we’ve got brain liver, kidney, adipose (which is your fat) and then muscles. And then I tried to put in all the different pathways that take place in each of these organs. Now you’ll see here that here’s our master, right? The liver is so key. I put it in the middle here. It does pretty much all of the different pathways. Everything happens in your liver. And I almost think of it like…it’s kind of like the liver’s got a finger in all of the other organs because it sort of knows what’s going on since it does the metabolism itself. It has a feeling for what’s happening in all of these other organs, because it’s got molecules in common with those. And so it just gets a sense for what’s happening in the whole body.

Again, we can break things down. Here’s your glucose metabolism, here’s your fat metabolism. Also, fats here gets stored as triacylglycerols…remember that if you’ve got a glycerol backbone here with three carbons, fatty acids could come off of that. So these are your fatty acids and together–this whole thing is called a triacylglycerol. So that’s something that the liver can do. Liver can also make ketones. So acetyl-CoA can get turned into little molecules that have ketone groups in them. That’s what a ketone is. And these guys will end up going out into your bloodstream and they go all throughout the body and can get used for energy. And then similarly, lactate–we’ll talk about that when we get to muscles. But the liver is important for converting the lactate back over to glucose so that it can generate more energy. Similarly, amino acids….generating that ammonia that can happen. And then we generate urea. That is also something that happens in the kidney over here. So again, the liver– master of all metabolism. It knows what’s going on in the rest of the body.

Here’s your brain and glycolysis. So using glucose and also using ketones…two things that the brain is very good at. And this is kind of an important area that’s getting more press these days because it is good if your brain can use ketones. You want to have both of those sources of energy in your brain. Muscles, muscles too can use ketones. But likewise, they also do a lot of glycolysis to generate energy, but you can also store glucose and glycogen in your muscles. Fatty acids can be broken down in your muscles…that can happen for energy. And similarly, a fast way of getting energy is to turn glucose over into lactate, but then that lactate gets recycled by coming into the liver…that’s something called the Cori cycle–for regenerating lactate into glucose. Likewise, even amino acids…you can have some of that metabolism in your muscles.

Let’s just pop over here to kidneys. Kidneys can do glycolysis, they can generate some ketones, and they also do have some of that amino acid metabolism. The main thing that the kidney is known for is helping to balance your electrolytes. So you want your potassium and your other, your divalent, your magnesium, so on. You need to have these guys be balanced and your kidney helps with that.

And then last thing…adipose. Remember this is your fat and this is how we store calories. Now fat cells do glycolysis…so that’s one of the ways that they get energy. But what they’re really mainly known for is to generate fatty acids. And then those fatty acids are going to get linked to that glycerol to make a triacylglyceride. That’s how we can get fat cells accumulating in our body is if we end up with too much fatty acids synthesis happening

Alright, lastly we’re going to focus on two hormones. Now you’ve got about 50 or so hormones in your body, and they all act like signals. So they’re signals…they basically are saying, “hey, turn something on” or “turn something off”. So the two examples I have here–insulin is a peptide hormone, and so it’s got about 51 amino acids. So it’s a little protein and it’s actually connected by some disulfide bonds. That’s what the yellow parts are here. So that’s kind of small compared to a regular protein, but it is bigger than say something like adrenaline. This adrenaline has got maybe nine carbons in it or something. So it’s quite a bit smaller than insulin is. So it’s just sort of more like a, an organic molecule. And these two (insulin & adrenalin) have opposing effects on some of these pathways that we’ve been talking about.

Here we can see up arrows, so that’s like turning a pathway on…and a down arrow is like turning a pathway off. And so if we look at what insulin does, we think of insulin as being a storage hormone. And so we’re storing the fuels that can be used for energy. Insulin is going to increase your glycogenesis. So glycogen…that’s how we store glucose. And then that word genesis…so that’s going to be make, so we are going to make more glycogen, which means we’re going to store more glucose that way. We’re going to turn off the glycogenolysis. So lysis means split, and so that is how we take…so if you remember what glycogen looks like–kind of a funny little shape like this, but each of these branches has lots of little glucose molecules. When we say split, we’re talking about splitting a glucose off of the glycogen. That does not happen when you have high levels of insulin, you end up going more into that storage mode. Similarly, fatty acid synthesis…that turns on because you’ve got extra calories and you need to store them somewhere. So you create fatty acids. And then those fatty acids go on to create some triglycerides. Then beta-oxidation is going to be down.

Now, if we come over here to adrenaline, we’re going to see that this is our fight or flight hormone. And so this uses energy. We need energy to do the fight or flight. And so we’re going to have to take those fuels out of storage…so we’re going to turn off the storage of the glucoses. We’re going to turn on the lysis of those glucoses off of the glycogen. And similarly, we’re going to turn down fatty acids synthesis. You don’t want to be storing your energy if you’re trying to run away from a tiger. And similarly, we’re going to turn on beta-oxidation. So that means we’re going to take those fats and turn those fats into energy. So that’s what adrenaline does for us in contrast to what insulin does.

So in conclusion, we talked about some of the key metabolic pathways. We talked about how we could have breakdown of metabolites and we can have synthesis of new ones, how energy storage is super important. We want to generate energy for our bodies, but if our bodies are consuming more than we need, then we need to be able to store the extra. Now that ends up being a problem…if we are always eating too much, and that’s one of the things that leads to obesity. And similarly, we talked about the different roles that organs play in respect to these different metabolic pathways. But I do want to remind you that the liver is the master of metabolism. And then the last thing talk about…we talked about hormones and I only gave you two examples here. We looked at insulin and adrenaline and we talked about how they serve as signals…on/off signals for the different pathways and how they work in contrast to each other…in opposition to each other. One helps you store energy, and the other one helps you release energy to carry out the things that your body needs.

Alright. We love you guys! Go out and be your best self today. And as always happy nursing!

 

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