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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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Vocabolario e note di pronuncia per questa lezione
Questa lezione di conversazione si basa sul video “Pyruvate Pathways & Metabolism”. Le parole che ritornano più spesso: pyruvate, cycle, alanine, glycolysis, pathway. Questo video contiene 177 frasi e 2436 parole da ripetere con lo shadowing. Il parlato dura 15:09. Chi parla ha un ritmo naturale di circa 161 parole al minuto, vicino a una conversazione quotidiana. Solo il 74% delle parole rientra nelle 3.000 più comuni dell’inglese, quindi il lessico è impegnativo.
Vocaboli chiave di questo video
15 parole del video che vale la pena imparare, con pronuncia e significato:
| Parola | Pronuncia | Significato |
|---|---|---|
| pathway sostantivo | /ˈpæθˌweɪ/ | via |
| muscle sostantivo | /ˈmʌs.əl/ | muscolo |
| oxygen sostantivo | /ˈɑksɪd͡ʒən/ | ossigeno |
| glucose sostantivo | /ˈɡluː.kəʊz/ | glucosio |
| acid sostantivo | /ˈæsɪd/ | acido |
| electron sostantivo | /ɪˈlɛk.tɹɑn/ | elettrone |
| convert verbo | /kənˈvɝt/ | convertire |
| generate verbo | /ˈd͡ʒɛn.ə.ɹeɪt/ | generare |
| molecule sostantivo | /ˈmɑ.lɪ.kjul/ | molecola |
| conversion sostantivo | /kənˈvɝʒən/ | conversione |
| vitamin sostantivo | /ˈvɪt.ə.mɪn/ | vitamina |
| enzyme sostantivo | /ˈɛn.zaɪm/ | enzima |
| lesson sostantivo | /ˈlɛs.ən/ | lezione |
| occur verbo | /əˈkɜː/ | verificarsi |
| alpha sostantivo | /ˈæl.fə/ | alfa |
I phrasal verb che sentirai
| Parola | Pronuncia | Significato |
|---|---|---|
| go through verbo | attraversare | |
| carry out verbo | /ˈkæ.ɹi aʊt/ | compiere, realizzare |
| point out verbo | additare |
La grammatica di questo video
Le strutture che chi parla usa di più, con le parole esatte del video:
| Struttura | Nel video |
|---|---|
| Forma passiva be + participio passato — conta ciò che accade, non chi lo fa | be covered · be shunted · is called |
| Present perfect have/has + participio passato — un’azione passata che conta ancora adesso | I've already told · I've shown · you've already learned |
| Frasi relative who / which + frase — un’informazione in più su una persona o una cosa | pathways, which will · pathway, which is · respirations, which is |
Pronuncia a cui fare attenzione
Chi parla usa 21 contrazioni e forme ridotte, come we're, don't, can't. Pronunciale nella forma breve, così come le senti.
- I suoni “th”: pathway /ˈpæθˌweɪ/, synthesis /ˈsɪnθəsɪs/
- I suoni “sh” e “zh”: conversion /kənˈvɝʒən/, infection /ɪnˈfɛkʃən/, tissue /ˈtɪʃ.(j)u/, occasionally /əˈkeɪʒənəli/, accomplish /əˈkɑm.plɪʃ/
- Parole lunghe — attenzione all’accento: metabolism /məˈtæb.əˌlɪz.əm/, primarily /ˈpɹaɪ.mə.ɹə.li/, occasionally /əˈkeɪʒənəli/, interactive /ˌɪn.tɚˈæk.tɪv/, adaptation /ˌæd.æpˈteɪ.ʃən/
I suoni difficili per chi parla italiano:
- /h/ — va soffiata, non è muta: whereas /(h)wɛɹˈæz/, hugely /ˈhjuːd͡ʒli/, dehydrogenase /diːˌhaɪdˈɹɒdʒəneɪz/, hypoxia /haɪˈpɔk.si.ə/
- Consonante finale — senza aggiungere una vocale dopo: glucose /ˈɡluː.kəʊz/, acid /ˈæsɪd/, convert /kənˈvɝt/, generate /ˈd͡ʒɛn.ə.ɹeɪt/, slide /ˈslaɪ̯d/
- /æ/ — più aperta della “e”: pathway /ˈpæθˌweɪ/, acid /ˈæsɪd/, alpha /ˈæl.fə/, arrow /ˈæɹəʊ/, whereas /(h)wɛɹˈæz/
Come esercitarsi con questo video
- Ascolta tutto il video una volta senza parlare e annota le parole che non conosci.
- Inizia a velocità 0,75×, fai shadowing frase per frase e torna alla velocità normale quando diventa facile.
- Registrati e confronta con l’originale, facendo attenzione a parole come pathway, muscle, oxygen.
Cos'è la tecnica dello Shadowing?
Shadowing è una tecnica di apprendimento delle lingue supportata da studi scientifici, originariamente sviluppata per la formazione dei traduttori professionisti e resa popolare dal poliglotta Dr. Alexander Arguelles. Il metodo è semplice ma potente: ascolti un audio in inglese di madrelingua e lo ripeti immediatamente ad alta voce — come un'ombra che segue il parlante con un ritardo di solo 1–2 secondi. A differenza dell'ascolto passivo o degli esercizi di grammatica, lo shadowing costringe il tuo cervello e i muscoli della bocca a elaborare e riprodurre simultaneamente i modelli di discorso reale. La ricerca dimostra che migliora significativamente la precisione della pronuncia, l'intonazione, il ritmo, il discorso connesso, la comprensione dell'ascolto e la fluidità del parlato — rendendolo uno dei metodi più efficaci per la preparazione alla prova di speaking dell'IELTS e per la comunicazione reale in inglese.