Shadowing Practice: Pyruvate Pathways & Metabolism - Learn English Speaking with Video
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Welcome back to Dirty Biochemistry.
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In this lesson, we're going to discuss the pyruvate molecule
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and how it is the most important molecule in determining which end product and which reaction pathway we ultimately choose to take.
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This lesson is on pyruvate metabolism.
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As a brief refresher, in the last lesson we discussed glycolysis and gluconeogenesis.
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When you start with glucose and ultimately form pyruvate downstream, that is glycolysis, shown here in red.
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If instead you move in the reverse direction, starting with pyruvate and going up to glucose, that is gluconeogenesis, shown here in blue.
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Now that we have that brief refresher in mind, we need to talk about what we can actually do with pyruvate.
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Now, I want you to think about pyruvate as the jack of all trades.
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It is one of, if not the most important molecules in any of these biochemical pathways,
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because pyruvate can at any point in time change itself
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or transform itself through a chemical reaction into one of four different products.
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So in all of these next examples, where we're going to go through four different biochemical pathways,
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we're going to start with the reactant of pyruvate and ultimately be able to form four different end products.
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The first pathway that pyruvic can take is to turn itself into lactic acid, aka lactate.
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When it does this, we're talking about the pathway referred to as anaerobic glycolysis.
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Now the word anaerobic means in the absence of oxygen.
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Anaerobic.
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There is no oxygen.
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This is glycolysis occurring without the presence of oxygen.
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Now normally, oxygen is hugely important in the ability to conduct glycolysis.
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Recall that glycolysis and all metabolic pathways have one goal in mind,
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and that is to work in tandem to form cofactors and reactants
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that can be used with one another to ultimately send everything
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to the electron transport chain to generate a massive amount of ATP.
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Now I want to take a step back and think about the big picture here.
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We have several different pathways and you need to know several different pathways, which will all be covered in this lecture series.
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There's glycolysis, gluconeogenesis, the Krebs cycle, a .k .a the TCA cycle.
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There is different protein formation and fatty acid synthesis.
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But I want you to relax for a second and keep the big picture in mind.
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All of these different pathways are working in tandem to form molecules
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that will ultimately all be shunted into the electron transport chain where you generate the most massive amount of ATP.
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That is the job of biochemical reactions occurring in the body.
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So if we keep that in mind and remember
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that oxygen is the ultimate or final electron acceptor in the electron transport chain,
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it should come as no surprise to you that in the absence of oxygen,
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which is to say that the electron transport chain will simply not work, there's no point in going through regular glycolysis.
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In this case, we're going to shunt pyruvate through anaerobic glycolysis because there's no point in doing regular glycolysis,
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again, because without oxygen, you don't have the final electron acceptor in the electron transport chain, so it's just a wasted reaction.
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Now, with that in mind, it should make a little bit of sense why instead of going from glucose to pyruvate
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and then sending pyruvate to the TCA cycle, we're just going to convert pyruvate to lactic acid.
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And that's done in the anaerobic glycolysis pathway, which is going to be the first pyruvate pathway that we talk about today.
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So I know that that was a pretty extensive aside,
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but I really want you to keep the big picture in mind because when you get lost in these details,
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you lose focus of what the actual purpose of these reactions are in the body.
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So the conversion of pyruvate to lactic acid is what's termed anaerobic glycolysis.
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And the enzyme that does this reaction is called lactate dehydrogenase, or LDH for short.
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Now, this enzyme is active in certain conditions, and I've already told you that this is anaerobic glycolysis.
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So it should come as no surprise that the main condition in which LDH is active is in low oxygen states.
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Now, clinically, low oxygen states occur in things like infection, hypoxia, ischemia, and heart failure.
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So when you ultimately become an upper level student and you go into the hospital,
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you will not be surprised to learn that in states such as these, we obtain lactate levels when we test people's blood,
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because an elevated lactate is telling us that the patient does not have adequate oxygenation,
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and it cues us that there may be some underlying infection or some underlying hypoxic or ischemic event going on.
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Now, in certain tissues...
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This is the pathway that pyruvate will primarily go through.
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And those tissues are shown here.
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The testes, the lens, white blood cells, the cornea, the medulla of the kidney, and red blood cells.
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This is simply a laundry list that you need to memorize.
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But I have a mnemonic to make it a lot easier for you.
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So I want you to think lactate when you can't make respirations.
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So when you can't make respirations, which is to say that you don't have access to oxygen,
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you will undergo anaerobic glycolysis and shunt pyruvate into lactic acid.
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So the mnemonic here is think lactate when you can't make respirations.
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T for testes, L for lens, W for white blood cell, C for cornea, M for medulla of the kidney, and R for red blood cells.
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If you remember this mnemonic, you can remember all of the tissues where anaerobic glycolysis has a propensity to occur.
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Now, in closing really briefly, I want to mention that the cofactor in the reaction catalyzed by lactate dehydrogenase is vitamin B3.
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And in all of these situations, if there is a cofactor that's worth remembering, I'll include it briefly on the slide.
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But that is the first possible pathway for pyruvate.
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The next possible pathway for pyruvate is actually being able to be turned into alanine.
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This conversion is referred to as the alanine aminotransferase pathway.
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And the enzyme that converts pyruvate to alanine is ALT.
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The cofactor here is vitamin B6.
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Now you may be asking yourself, why would we want to turn pyruvate into alanine?
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And the reason is something called the Cahill cycle.
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So pyruvate is not able to jump between muscle and liver.
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It's simply unable to do it.
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So in order to recycle carbons between the muscle and the liver,
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we actually have to disguise pyruvate as alanine or glucose to be able to make this a possibility.
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So let's take a second and show you exactly what the Cahill cycle is and why it's such an advanced
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adaptation that is a really remarkable thing.
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So here on the left, you see a liver and here on the right, you see a muscle.
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Obviously, I'm simplifying these drawings to show you some biochemical pathways.
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So starting with pyruvate, you can turn pyruvate into alanine using the ALT enzyme that I've shown you on the previous slide.
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This conversion will also use up glutamate and spit off alpha -ketoglutarate.
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You need to memorize these are cofactors.
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So it's pyruvate plus glutamate goes to alanine plus alpha -ketoglutarate.
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Since pyruvate cannot jump between muscle and liver, alanine can.
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That is why we convert the pyruvate into alanine.
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Once you have the alanine, the alanine can go from the muscle into the liver.
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Sneaky little alanine.
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Alanine, once it's in the liver, can be converted back into pyruvate using alpha -ketoglutarate and spitting off a glutamate.
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So it's the same reaction in the muscle, just backwards.
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Once we have the pyruvate, we need to get the pyruvate back over into the muscle so that we can keep the cycle going.
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But I told you that pyruvate cannot jump from liver to muscle or from muscle to liver.
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So how do we accomplish this?
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Well, in the Cahill cycle, we actually hack the system and use gluconeogenesis, which you already learned about in the first lesson.
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So we go back up from pyruvate to glucose.
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And that's just gluconeogenesis, folks.
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Once we have the glucose, the glucose can jump from the liver to the muscle.
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And then once in the muscle, we use glycolysis to go down from glucose to pyruvate.
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Talk about an amazing system.
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Look how awesome that is.
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The red arrows shown on this slide on the left in the liver going from pyruvate up to glucose,
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that is just gluconeogenesis, which you've already learned about.
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And then on the right in the muscle, the red arrow going down from glucose to pyruvate, that's just glycolysis.
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And you already know that.
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So it's really the glucose and the alanine that's able to move between liver
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and muscle to bring pyruvate across from muscle to liver.
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And the whole reason that we do this is because pyruvate is a carbon molecule,
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and we need to move those carbon molecules around to make use of certain materials in the body.
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So this is the reason that we turn pyruvate into alanine.
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It's to make use of the Cahill cycle.
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Now, the Cahill cycle itself refers to everything you see here with red arrows.
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It's the constant conversion from pyruvate to alanine, from alanine back to pyruvate, from pyruvate to glucose, from glucose back to pyruvate.
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That cycle continues indefinitely while we regenerate glutamate and alpha -ketoglutarate on the side and use them as cofactors.
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This is the Cahill cycle.
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Now that's the reason that we would convert pyruvate to alanine.
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And to quickly summarize so that you don't get lost, from pyruvate to lactic acid is anaerobic glycolysis, which occurs in low oxygen states.
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From pyruvate to alanine, that is to shunt around and cycle.
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carbon molecules using ALT through the Cahill cycle.
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The next option for pyruvate is to be converted into oxaloacetate.
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And the enzyme that does this conversion is pyruvate carboxylase using a cofactor of biotin.
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Now we're not going to talk about this pathway too much,
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but the goal here is to use oxaloacetate as an available reactant for either gluconeogenesis and or the TCA cycle.
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Oxaloacetate can contribute to gluconeogenesis, but also the TCA cycle.
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Truth be told, this is really just a fail safe in case the body needs to generate an additional reactant to push
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it in either direction of gluconeogenesis or the TCA cycle.
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So pyruvate has a lot of jobs, and one of them is to use pyruvate carboxylase
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and biotin as a cofactor to generate oxaloacetate to simulate gluconeogenesis or the TCA cycle in certain situations.
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That's really all you need to know about that pathway from pyruvate.
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Not too much to know, but just something to keep in mind.
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The final and perhaps most important pathway for pyruvate is its ability to be converted into acetyl -CoA.
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The reason that this is so important is because acetyl -CoA is the chief reactant of the TCA cycle.
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So without the conversion of pyruvate to acetyl -CoA, we would never be able to complete TCA cycle.
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Now the enzyme that converts pyruvate to acetyl -CoA is pyruvate dehydrogenase.
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Not only should you memorize pyruvate dehydrogenase, but you also need to memorize the five cofactors, vitamin B1, vitamin B2, vitamin B3,
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vitamin B5, and lipoic acid.
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Please, please, please memorize this.
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It is extremely high yield.
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Now, I told you, acetyl -CoA is the chief reactant of the TCA cycle.
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So if you never convert pyruvate into acetyl -CoA, then you can never provide the reactant for the TCA cycle to spin the TCA cycle
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and generate the carbon dioxide necessary to carry out a series of reactions that in unison, across all reactions,
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will ultimately make use of different products to go to the electron transport chain and generate massive amounts of ATP.
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That's the big picture.
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The last thing that I want to point out is
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that you'll notice that in the reactions of going from pyruvate to oxaloacetate and from pyruvate to acetyl -CoA, these are irreversible reactions.
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They are one -sided arrows.
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But going from pyruvate to lactic acid or pyruvate to alanine are reversible reactions.
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And what you need to know about the differences here are
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that oxaloacetate and acetyl -CoA are formed from pyruvate in the mitochondria,
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whereas pyruvate to alanine and pyruvate to lactic acid are formed in the cytosol.
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Please memorize that because occasionally test writers have been known to ask you exactly where these reactions take place.
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I want to pause for a second
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and summarize the high yield points from this lesson
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because there was a lot of information and I don't want you to get lost in the details.
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Glycolysis, gluconeogenesis, different types of synthesis, whether it's fatty acids, ketones,
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or proteins, all of the chemical reactions in the body work together to generate an interactive set of reactants,
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products, and cofactors that can ultimately go to the electron transport chain and generate a massive amount of ATP for the body.
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We'll talk about the electron transport chain in another video in this series, but you should know right now
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that the job of the electron transport chain is like a gigantic machine
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that generates an enormous amount of energy for the body.
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So all of these reactions have to find some way to work together to form everything needed to make that a possibility.
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In low oxygen states where electron transport chain can simply not happen, pyruvate will go to lactic acid in low oxygen states such as infection,
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ischemia, hypoxia, and heart failure.
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LDH catalyzes that reaction.
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In other scenarios, pyruvate will turn into alanine through ALT.
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And the reason
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that we do this is to satisfy the Cahill cycle's ability
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to recycle carbon molecules from the liver to the muscle and vice versa.
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In some situations, pyruvate can be turned into oxaloacetate using pyruvate carboxylase.
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Oxaloacetate can stimulate gluconeogenesis, and it also has a secondary stimulating effect on the TCA cycle.
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And lastly, pyruvate can be turned into acetyl -CoA by pyruvate dehydrogenase with five important cofactors.
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Acetyl -CoA is the chief reactant in the TCA cycle, and without the ability to convert pyruvate into acetyl -CoA, it could never happen.
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Acetyl -CoA and oxaloacetate are formed in the mitochondria, whereas alanine and lactic acid are formed in the cytosol.
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That's it for this video.
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Rewatch it if you need to, but pyruvate metabolism is extremely important.
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Vocabulary and speaking notes for this lesson
This speaking lesson is built on the video “Pyruvate Pathways & Metabolism”. The speaker keeps coming back to these words: pyruvate, cycle, alanine, glycolysis, pathway. This video has 177 sentences and 2436 words to shadow. The speech runs for 15:09. The speaker talks at a natural 161 words per minute, close to everyday conversation. Only 74% of the words are among the 3,000 most common in English, so the vocabulary is demanding.
Key vocabulary in this video
15 words from the video worth learning, with pronunciation and meaning:
| Word | Pronunciation | Meaning |
|---|---|---|
| pathway noun | /ˈpæθˌweɪ/ | A footpath or other path or track. |
| muscle noun | /ˈmʌs.əl/ | A contractile form of tissue which animals use to effect movement. |
| oxygen noun | /ˈɑksɪd͡ʒən/ | The chemical element (symbol O) with an atomic number of 8 and relative atomic mass of 15.9994. It is a colorless and odorless gas. Sometimes called elemental… |
| glucose noun | /ˈɡluː.kəʊz/ | A simple monosaccharide (sugar) with a molecular formula of C₆H₁₂O₆; a principle source of energy for cellular metabolism. |
| acid noun | /ˈæsɪd/ | A sour substance. |
| electron noun | /ɪˈlɛk.tɹɑn/ | The subatomic particle having a negative charge and orbiting the nucleus; the flow of electrons in a conductor constitutes electricity. |
| convert verb | /kənˈvɝt/ | To transform or change (something) into another form, substance, state, or product. |
| generate verb | /ˈd͡ʒɛn.ə.ɹeɪt/ | To bring into being; give rise to. |
| molecule noun | /ˈmɑ.lɪ.kjul/ | The smallest particle of a specific element or compound that retains the chemical properties of that element or compound; two or more atoms held together by… |
| conversion noun | /kənˈvɝʒən/ | The act of converting something or someone. |
| vitamin noun | /ˈvɪt.ə.mɪn/ | Any of a specific group of organic compounds essential in small quantities for healthy human growth, metabolism, development, and body function. They are found… |
| enzyme noun | /ˈɛn.zaɪm/ | A biomolecule that catalyses a biological chemical reaction: either a globular protein with this function or an RNA molecule with this function. |
| lesson noun | /ˈlɛs.ən/ | A section of learning or teaching into which a wider learning content is divided. |
| occur verb | /əˈkɜː/ | To happen or take place. |
| alpha noun | /ˈæl.fə/ | The name of the first letter of the Greek alphabet (Α, α), followed by beta. In the Latin alphabet it is the predecessor to A. |
Phrasal verbs you will hear
| Word | Pronunciation | Meaning |
|---|---|---|
| go through verb | To travel from one end of something to the other. | |
| carry out verb | /ˈkæ.ɹi aʊt/ | To hold while moving it out. |
| point out verb | To identify among a group of similar subjects, or in a scene where the subject might not be readily seen or noticed, with a gesture of the body. | |
| step back verb | /stɛp ˈbæk/ | To stop what one is doing and evaluate the current situation. |
| use up verb | To consume, deplete, expend, or exhaust. |
דקדוק בסרטון הזה
המבנים שהדובר משתמש בהם הכי הרבה, עם המילים המדויקות מהסרטון:
| מבנה | בסרטון |
|---|---|
| סביל (Passive voice) be + past participle — הדגש הוא על מה שקורה, לא על מי שעושה את הפעולה | be covered · be shunted · is called |
| הווה מושלם (Present perfect) have/has + past participle — פעולה שקרתה בעבר ועדיין יש לה חשיבות או השפעה עכשיו | I've already told · I've shown · you've already learned |
| משפטי זיקה (Relative clauses) who / which + clause — מידע נוסף על אדם או דבר | pathways, which will · pathway, which is · respirations, which is |
Pronunciation to watch
The speaker uses 21 contractions and reduced forms, such as we're, don't, can't. Say them the short way, as you hear them.
- The “th” sounds: pathway /ˈpæθˌweɪ/, synthesis /ˈsɪnθəsɪs/
- The “sh” and “zh” sounds: conversion /kənˈvɝʒən/, infection /ɪnˈfɛkʃən/, tissue /ˈtɪʃ.(j)u/, occasionally /əˈkeɪʒənəli/, accomplish /əˈkɑm.plɪʃ/
- Long words — get the stress right: metabolism /məˈtæb.əˌlɪz.əm/, primarily /ˈpɹaɪ.mə.ɹə.li/, occasionally /əˈkeɪʒənəli/, interactive /ˌɪn.tɚˈæk.tɪv/, adaptation /ˌæd.æpˈteɪ.ʃən/
How to practise with this video
- Listen to the whole video once without speaking and note the words you do not know.
- Start at 0.75× speed, shadow it sentence by sentence, then go back to normal speed once it feels easy.
- Record yourself and compare with the original, paying attention to words like pathway, muscle, oxygen.
מהי טכניקת השאדואינג?
שאדואינג היא טכניקת למידת שפה מבוססת מדע שפותחה במקור להכשרת מתורגמנים מקצועיים ופופולרית על ידי הפוליגלוט ד"ר אלכסנדר ארגואלס. השיטה פשוטה אך עוצמתית: אתה מקשיב לאודיו באנגלית ילידית וחוזר עליו בקול רם מיד — כמו צל העוקב אחרי הדובר עם עיכוב של 1–2 שניות בלבד. בניגוד להאזנה פסיבית או תרגילי דקדוק, שאדואינג מכריח את המוח והשרירים בפה לעבד ולשחזר דפוסי דיבור אמיתיים בו זמנית. מחקרים מראים שזה משפר משמעותית את דיוק ההגייה, האינטונציה, הקצב, הדיבור המחובר, הבנת השמיעה ושטף הדיבור — מה שהופך אותו לאחת השיטות היעילות ביותר להכנה לIELTS Speaking ולתקשורת באנגלית בעולם האמיתי.