JN

Lecture 12: Cellular Respiration 1

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Hi everyone.

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Welcome to your online lecture for today where we're going to be continuing our discussion of metabolism to include the heterotrophs like yourself.

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We're going to focus on cellular respiration and we're going to do this in two parts.

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And what we're really focusing on is how it is that cells in heterotrophs, like you have to harvest the chemical energy out of organic molecules that autotrophs, like plants and other photosynthetic things, actually produce for us to use.

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Technically, they're producing them for themselves, but we take advantage of the fact because we need some carbon sources, usually in the form of sugars and fats and sometimes amino acids to be able to metabolize so that we can get an electrons that can do work for us.

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Now, many of the carbohydrates that we take in unfortunately end up getting converted into fat here, which is the joke of the Beatrice the Biologist cartoon, because the fat cells think that we should keep it all 'cause we might need it all someday.

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And that's kind of the unfortunate consequence of how much we consume and how we don't use all of it for cellular respiration in this particular lecture, because it's kind of heavy and it's it's content that tends to confuse people and feels like a lot of steps and a lot of moving parts and a lot of things that you need to to memorize, which is better if you actually understand it.

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I tried to keep it light by introducing some of my favorite characters from one of the oldest, longest running sitcoms in history, namely The Simpsons, in particular, Homer Simpson, partly because Homer Simpson loves the sugary treat, particularly Donuts.

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And then as we see after we talk about cellular respiration, we think about fermentation.

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Fermentation is another process by which we can harvest chemical energy in the short term, and that's a means by which one of Homer Simpson's other favorite digestible items is produced.

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Beer is made by fermentation.

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And so Homer just seems like a really great subject for studying cellular respiration.

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And I'm a child of the 80s and the 90s and Simpsons, we're very popular, have been for many decades now.

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And so when we think about cellular respiration, what we're really talking about is the chemical opposite of photosynthesis, breaking down the organic molecules, sugars, namely in the form of glucose and converting the stored energy in glucose into something that we can use, which is our cellular energy currency or ATP.

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Now that being said, the chemical pathway is the reverse of photosynthesis.

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The biochemical pathway is very different.

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It happens in a completely different organelle with lots of different enzymes and substrates.

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And so make sure you recognize that even though the chemical reaction seems a little misleading, it seems like the same thing backwards and forwards.

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It is a little different in the processes by which both of those pathways happen.

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Photosynthesis and cellular respiration are complementary to each other, but the ways that we've evolved to be able to do them are different.

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So we're going to think about taking in organic molecules like sugar requiring oxygen as an electron acceptor.

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That gets reduced ultimately in the process after we've oxidized the sugar molecule down into waste products that are unusable for us, namely carbon dioxide and water, but also producing energy as a byproduct.

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And we're going to see the energy that we get out of the sugar molecule directly is going to be electrons.

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Electrons will do the work for us of producing ATP molecules that we're going to use for lots of cellular processes to maintain our energy budget.

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And so photosynthesis, as we've already talked about in cellular respiration, really are the processes that are providing any energy for our lives.

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Because remember what I told you, staying alive takes work.

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And so in our ecosystems across the planet, energy first and foremost comes from the sun.

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There's all kinds of solar energy hitting the planet, most of which we can't even actually use.

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Plants are able to harvest about 1% of the energy that's actually hitting the surface of the planet.

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And by plants, I'm including all the other photosynthetic things on the planet as well, which is actually overwhelmingly represented by the top 200 meters of all of the world's oceans, much more so than any terrestrial environment.

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And so photosynthesis, as we learned, is where solar energy is captured by pigments and chloroplasts that excite those pigments to donate electrons that are generally stripped away from water molecules and bring in carbon dioxide gas and use those electrons to link carbon molecules together and build larger structures in the form of sugar.

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And so the products of this process are going to be carbohydrates and oxygen, molecular oxygen as waste, which is super useful for us because molecular oxygen is one of the reactants that we need in order to do cellular respiration.

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So we take in sugar as a reactant.

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We use oxygen in order to combust this sugar.

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In reality, oxygen becomes the ultimate electron receptor that is going to be reduced in the whole process.

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And we end up releasing carbon dioxide and water as waste.

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And carbon dioxide is easy to get rid of because it's a gas that is happy to get out of our cells and we're water based organisms anyway, so water as a waste product doesn't really hurt us too much.

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We require lots and lots of mitochondria to be able to do this.

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We're going to see this is the organelle of choice that is for completing cellular respiration.

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We'll also see a small part of it happens in the cytoplasm, but largely the bulk of it occurs in these specialized organelles that have evolved from alpha proteobacteria that were ingested billions of years ago and maintained in this, in this context inside of eukaryotic cells.

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And as any energetic metabolic process includes, some of this energy that we do is going to be lost to the form of heat because nothing is totally efficient when it comes to metabolizing organic molecules.

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And so our cells are meant to use the mitochondria, chloroplasts or the use the cytosol, the and, and mitochondria and the enzymes that are present in those to basically combust sugars.

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Now, it's not burning sugar in the sense of, you know, you put it on a stove and you melt it in a pot.

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It's not exactly like that, but it is still a combustion process where oxygen is actually used to break apart glucose molecules.

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Now the chemical reaction, as I mentioned, is a little bit misleading.

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Once you see the biochemical process and the the the whole sum of steps for how this works, it starts to make a lot more sense why oxygen is involved.

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It's because it is one of the most electronegatively stingy things that is very readily abundant in our cells and is going to be the ultimate guy at the end of the whole process that catches our tired electrons after we've used them to do a bunch of work.

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And where do those electrons come from, Right?

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They come from that sugar molecule.

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They're hidden in the bonds between the carbons and between the carbons and hydrogens.

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And we're going to break apart that molecule and we're going to use those electrons to do work for us.

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OK.

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So keep in mind this particular reaction, glucose combusted with oxygen.

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Black arrow, black arrow, black arrow, big black box of stuff that happens in the middle gives us multiple molecules of carbon dioxide which have been separated from each other.

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They were initially stuck together in that glucose molecule and a couple of molecules of water.

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And so this is the opposite of photosynthesis, right?

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Where you're using carbon dioxide and you're stripping electrons out of water in order to build sugar and oxygen.

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And in this case, instead of utilizing ATP, we're going to produce ATP because this is a process where it's going to be exergonic.

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You're going to break that molecule apart and release the energy stored in it, or use the release energy to create another form of energy, transforming it to something else, which is ATP.

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Remember that in photosynthesis, the opposite is endergonic.

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In order to build something much more complex and larger than the sum of the parts, it requires an investment of energy, which is why photosystem 2 has to make ATP first before the Calvin cycle can proceed.

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Requires work when you're decreasing entropy, making less chaos in a system.

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And so oxygen's involvement in this comes from its strong electronegativity.

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That's really electrons stingy and it's actually going to help sort of vacuum electrons all the way through the part of this process that's making the bulk of the ATP in our mitochondria.

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Remember that electrons are excitable, but as they do work, they tend to get tired, they tend to get worn out, they get jumped up to that high energy state.

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It gets them to do work and then they sort of get tired and they either have to be collected by something and used in a bond or they have to be re excited in order to do that work again.

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Remember we don't lose or or dispose of electrons.

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We always catch and recycle them.

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They always end up in some molecule.

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And that's because electrons are super reactive and we don't want them to end up in the wrong place.

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Like oxygen alone, right?

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Oxygen alone, hanging out with some electrons is bad.

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It's very, very interactive.

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That's what we call reactive oxygen, and we know it's really damaging to our DNA and our proteins.

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So what we do is try to guarantee that if we hand off electrons to oxygen at the end, we also give it some protons to neutralize it into actual water, which is harmless for us.

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But the process of utilizing the electrons that are stored in the bonds of glucose and getting them to do work is imagining that as they get tired, they're sort of free falling down an energy hill, right?

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And so here we've got our friend Lisa Simpson and her friend Ralph Wiggum.

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And Ralph is rolling down a hill, right?

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So he's got real high potential energy as he's starting at the top of the hill, and that transfers into kinetic energy.

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And then as he gets to the bottom of the hill, most of the energy is gone.

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And so electrons experience this as they move through the part of the pathway that they're involved in through their work, which ultimately results in the production of ATP.

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And so remember, it's this process of sort of falling down a hill as they run out of energy.

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And so we can use the chemical bonds that are present in glucose and convert them into chemical bonds that are present in ATP, which we actually use in our cells.

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Something to remember as an aside before we continue thinking about cellular respiration.

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Cellular respiration is not the same thing as anatomical or physiological respiration, as UN breathing in and out.

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Not the exact same thing.

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And all organisms are gonna respire in some way.

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Anybody doing cellular respiration, even plants, do cellular respiration.

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They have to metabolize sugars for their own processes of growth and building things and responding to their environment.

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And they don't have lungs, but they're still doing cellular respiration.

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When we think about respiration in terms of us as air breathers, that's often what we're talking about, is lung breathing.

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This is cellular respiration.

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And so this is a little different.

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This is where we think about using oxygen for an actual process, a metabolic process.

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When we think of breathing respiration, that's where we're exchanging gases through our lungs.

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We bring in oxygen, re release CO2.

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That process is supporting cellular respiration on the cell level.

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OK, But actual breathing respiration and cellular respiration are two different processes that we're talking about.

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That eventually breathing respiration actually feeds into cellular respiration.

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As you're bringing in oxygen from your external environment, you use it in cellular respiration.

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As you produce CO2 waste in cellular respiration, you release it to the environment by actually breathing.

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So later we're going to talk about the respiratory system and the circulatory system, and we will address breathing respiration later.

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Just remember to keep those two things straight for now.

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And so cells are going to capture energy from electrons that are stripped out of organic molecules that go through a series of steps to do work and are ultimately going to hand it be handed off to oxygen at the end.

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And so glucose is the one that loses its hydrogen atoms because that's where the electrons are being stored.

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And it's going to become oxidized.

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And so by losing its electrons, remember, it's going to be oxidized.

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If it gained electrons like carbon dioxide does in photosynthesis, that's making it reduced.

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OK, So here we're stripping the the hydrogen atoms.

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Here is glucose, C6H12O6.

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Notice it's going to have its hydrogen atoms stripped, and look what it becomes.

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It becomes carbon dioxide.

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Where do those hydrogen atoms go?

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Well, the only place to add them is on to the oxygen that it's starting with in the reactants.

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And you'll notice that's what happens.

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We end up adding the hydrogen atoms to the oxygen atoms to produce water, and so oxygen is going to gain those hydrogen atoms.

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It's getting the electrons, which means that it's becoming reduced to convert it into actual water.

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Remember always that inside of a hydrogen atom is one proton and one electron, and they're attracted to each other, and that is the simplest atom.

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And so we hide electrons in hydrogen atoms because they're neutral and they're safe and they're not reactive and they don't change the pH of a solution.

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So we hide them together.

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And what we do is we move these HS around in reactions, and the electrons are hidden in those hydrogen atoms, but they're neutral and happy and satisfied and not reactive.

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And so you're going to watch anywhere the HS go.

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That's the thing that's being reduced to form a new product.

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OK.

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And so this gain of hydrogen atoms on oxygen causes it to form a new molecule.

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And oxygen is being reduced in this process as expected, because it's the electronegatively stingy one, right?

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So we're going to make sure we follow those.

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So the steps of cellular respiration occur in three large parts.

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We're going to break this particular lecture into two parts.

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We're going to discuss the 1st 2 main parts of cellular respiration.

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And then in the next small lecture, we're going to discuss the last part where there's a big payout of ATP production.

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And we're going to talk very briefly about the process of fermentation, which is an offshoot of cellular respiration.

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When conditions make it so that you can't compete the complete cellular respiration successfully, it's sort of a shorter way of maintaining your energy budget temporarily.

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And so cellular respiration is combined of a series of reactions that ultimately produces ATP from an electron transport chain at the end.

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And I want you, as we talk about this, to think about the similarities that we may have seen in the thylakoid membranes in chloroplasts.

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And you'll look for very similar mechanistic commonalities between the two, OK?

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It'll also make the differences pretty clear as well.

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So cellular expiration has four steps, the first of which is called glycolysis.

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And so that prefix glyco means sugar and lysis or to lysed something is to break it down, OK.

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And so we've got a six carbon ring of glucose and we're going to break it down into two, three carbon molecules called pyruvate, OK?

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This is a great overview slide.

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This is something that as we add the parts to it, you should consider drawing it out so that in your motor memory you can recall these individual steps, what they're called, what they're producing, and then where everything is inside of the cell, 'cause you'll notice that this first part actually happens in the cytoplasm.

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So it's not in the mitochondria yet, it happens out in the cytoplasm where we break it down into pyruvate.

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And the next step is gonna be pyruvate processing.

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We need to break that down.

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One more step 'cause remember, the goal is to take these glucose molecules and break them apart, right, And steal the electrons that are holding the atoms together.

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It's like taking a necklace with beads on it, getting rid of all the beads and taking the string, right?

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It's taking the connections out.

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And remember, every bond that we break is gonna have two electrons.

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Every bond you break, every electron you take, it's going to have two electrons and a bond.

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OK.

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And so we're going to think about pyruvate processing next.

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That's the three carbon, dude.

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That glucose is going to be broken down into two of those.

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Pyruvate is then going to travel into the mitochondria through a transporter and there it's going to be modified or oxidized, which means we're going to steal some more electrons from it, break one more bond, and we're going to convert it into A2 carbon thing called acetyl COA.

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Acetyl COA is then going to be fed into a cycle called the citric acid cycle, which kind of resembles the Calvin cycle a bit in the way that it's run mostly different intermediates.

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Couple of intermediates are the same and it's going to be oxidized further down.

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The whole goal is to take the six carbon ring and break it apart into individual carbon dioxide molecules.

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And everything that comes out of these three separate subparts is going to end up going to the last main part.

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I guess it's actually really 4 reactions, 4, four major steps.

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Those are going to end up going to an electron transport chain and doing a process called oxidative phosphorylation.

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OK.

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So oxidation is stealing electrons and phosphorylation is adding phosphates to things.

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And so it would make sense that and we're adding phosphates to things.

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We're making a product ATP that has phosphates on it.

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OK.

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And so we're going to think about each step of this and what we glean from each step and where do they go to drive this process at the end, all the while remembering that this is happening inside of your cells right now.

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So First things first, sugar breaking.

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We have our friend Homer here eating a doughnut appropriate that he's about to do some glycolysis with it in his mitochondria.

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So remember that prefix glyco means sugar and lysis means breaking.

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And so that's what we're going to do.

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We're going to take sugar molecule and we're going to break it apart in half, OK.

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And so a lot of this begins in your digestive tract.

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We're going to learn a little later when we talk about nutrition and digestion that the breakdown of carbohydrates tends to start in your mouth.

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But as it goes through your stomach and into your intestinal tract, that's where a lot of those sugars are going to be absorbed into your cells.

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And then your cells are going to transport those sugar molecules in to the cytoplasm and start breaking them down.

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OK.

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And there's a series of about 10 reactions.

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I want you to understand what's happening here in a broad overview.

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I don't want you to memorize any structures.

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I do want you to think about what's consumed and what's produced.

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But if we sort of walk through stepwise and then maybe we watch sort of a summary video of what happens, it'll become clear these particular pathways are going to come across your desk again.

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If you take biochemistry later, you're really going to talk about these a lot.

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Probably also if you take anatomy and Physiology and then later maybe in cell bio, if you learn, if you take cell bio, you might learn this again.

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But it becomes important later to understand how this process works so that you can think backwards about what happens when this process goes wrong.

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What happens when you're not able to breakdown sugars?

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What happens if you have a mutation in one of the enzymes in these pathways?

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And so it's having a good strong foundation for all the parts of cellular respiration is really important.

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And the more you work on it in this class, the better you're going to feel about it later.

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OK, so sugar breakdown, we're going to see that we have three or two, two main phases for being able to breakdown sugar.

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And this is going to happen in the cytoplasm.

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The first is using a little bit of energy to modify glucose and make it unstable and then start breaking apart, and then take some of those resources back to make additional energy.

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When you see these numbers, it seems kind of weird, but when you see the actual pathway, you'll understand.

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In most businesses, you gotta invest a little money to make a little money, right?

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And the same thing is true of glycolysis.

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You have to invest a little bit of ATP in an energy investment phase to modify glucose to make it unstable, and then take a bunch of phosphates back again and make some additional ATP that you didn't even start with.

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So you're investing 2 and you're making four, which means you're netting 2 that you didn't have when you started.

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So we're going to talk about not only how we produce a tiny bit of ATP, not enough to keep you alive, just enough for, you know, chemical purposes using phosphates, but we're also going to talk about how we're going to start stealing electrons by breaking apart sugar molecules.

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In the very first step, what we're going to do is we're going to take electrons by breaking their bonds.

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We're going to hand them off to an electron carrier, and that electron carrier is going to go off to the electron transport chain.

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It's very similar to what we saw in photosynthesis where we take electrons, we hand it off to something that is easily reduced but happy to be oxidized when it gets to where it's going, something that'll hold it for a while, but not stingy enough to keep your electrons.

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OK.

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And then we're going to think about the next steps after that.

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So Glysis is consisting of those two phase.

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First you have to pay off pay in a little energy, but you're going to get that back and two more.

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So there's a little bit of a payoff, and that's simply because of how we're trying to modify glucose in order to begin the process of trapping it in a cell and breaking it down by oxidizing its bonds.

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And so this is our electron carrier, NAD Plus.

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You may remember when I talked about metabolism, I showed you that NAD plus can hold two electrons, one on a nitrogen atom and one on a carbon atom, and will hold them temporarily until they can be handed off to an electron transport chain because they're actually more stable as NAD plus than they are holding extra electrons.

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So remember that if you give NAD Plus one electron, it becomes just plain NAD.

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If you give it a second electron, it becomes NAD minus.

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That makes it reactive.

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And we don't want that to be the case.

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So we're also going to give it a proton and it just becomes regular old stable NADH, hiding two electrons, but not really wanting to go out and interact with anybody.

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OK, so this is the first thing that happens.

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And this is where you're going to be like, there's too much chemistry in my biology, but you just kind of have to recognize it's a metabolic pathway.

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Every enzyme that's involved is going to help trap and start converting and making these sugar molecules unstable so that they can be broken in two halves, OK.

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And so here's our glucose molecule.

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We've got 123456 carbons.

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And what we're kind of going to do is we're going to end up breaking the molecule sort of across in half.

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So we have 3 carbons and three carbons, and the products are just a tiny bit different from each other.

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But we'll notice that we end with a molecule G3P, which is very similar.

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That was what was produced in photosynthesis in the Calvin cycle.

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Remember 1/2 a sugar, right?

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OK, so the first thing that happens here is the very first enzyme is going to be hexokinase.

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Look at the name.

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HEXO means 6 kinase, means I had phosphates to things, and so it's going to take this 6 carbon sugar and it's going to remove a phosphate off of ATP and it's going to phosphorylate the sugar right here on the 6th carbon, making glucose 6 phosphate.

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See the name.

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It tells you exactly what happened.

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And the reason that it does that is to trap glucose in your cells, like the lining of your intestines and convert it into something slightly different than regular glucose.

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So it always seems like, well, the glucose is all gone.

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We used it all, but in really you just converted it into something else that can't get back out of your cells and looks like makes it look like your glucose levels are low.

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So you'll just keep bringing more into the cells.

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OK.

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And then what's going to happen is a slight little rearrangement here.

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We're going to have phosphogluco isomerase.

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We're going to see that we're going to make it look like a pentose ring now instead of a hexo spring.

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And we've got these same groups that are on either end.

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And to balance it out, we're going to use phospho fructokinase because of this is now fructose.

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Remember, when you have glucose, it's or, or sucrose, it's glucose and fructose.

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So it's easy to convert glucose into fructose if you just move the molecule around a little and make it A5 carbon sugar.

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And so we're going to end up phosphorylating it again so that it's even on both sides.

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And then we're going to end up breaking this in a slightly unequal halves, OK.

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And so here's your investment of two phosphates.

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The 1st is to trap it in the cell.

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The second are to help make it unstable.

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And so we're not trying to add additional functional groups to this molecule as we break it down.

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Those phosphates are only temporary.

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They're just kind of like placeholders for the enzymes to get a hold of the molecule and start pulling it apart.

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Eventually those phosphates get taken right back off and put right back onto ADP to make more ATP.

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They get recycled.

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We're trying to break this down into smaller bits, not make bigger ones.

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And so this enzyme called aldolase is going to end up breaking this fructose 16 biphosphate bisphosphate.

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Notice it's on the one in the six carbon.

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There's phosphates on both.

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That's the name.

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It's going to break it in half into two different types, glyceraldehyde 3 phosphate, it's still 1 phosphate and dihydroxyacetone phosphate, D HAP.

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Now they're very similar to each other, but they can be interconverted back and forth depending on the presence of an isomerase, right?

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And so we're probably going to end up using G3 PA lot more than DHAP because we want two starting molecules that are the same going into the energy payoff phase to make pyruvate.

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We don't want to have to rescramble and do a different set of biochemical reactions to make the same thing.

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So we're going to convert D AAP into G3P, and we got two molecules of that.

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So we took a six carbon ring and broke it into two halves.

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In that case, how many bonds did we break?

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Did we get anything out of that?

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We ended up breaking a couple of bonds, didn't we?

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Yeah, we break A6 carbon thing into two halves.

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We broke a bond here and a bond here.

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So we broke two bonds.

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Right now we're going to see that we're going to scavenge some electrons off of this molecule using this trios phosphate dehydrogenase.

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Look at the name.

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Triose is 3 sugar, 3 carbon sugar phosphate.

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I'm using inorganic phosphate to do my work dehydrogenase.

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I am taking hydrogen atoms off of this thing so I can steal electrons.

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Now watch what happens.

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So notice this H right here, it's got an electron in it, right?

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And there's two molecules of this.

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I'm going to steal and swap it with a phosphate PO4 to satisfy this carbon because it's got to have a placeholder.

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I can't just leave it unbonded.

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And that doesn't work.

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But I've steal this H and I give do it twice.

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I give the electrons actually looks like I'm doing it four times.

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No two molecule.

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Yeah, that's right.

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I'm going to steal this these hydrogen atoms off of G3P and I'm going to hand them over to NADH and it's going to give me this right here, this one, three bisphosphate glycerate, bisphosphoglycerate.

27 minutes 55 seconds

So glycerate is a derivative of glyceraldehyde.

27 minutes 58 seconds

Now it's phosphorylated twice.

27 minutes 59 seconds

We don't want that.

28 minutes

We want to take those phosphate residues back and put them back onto ADP.

28 minutes 6 seconds

OK.

28 minutes 6 seconds

And we're aligning ourselves to create carboxyl groups on this sugar intermediate that are easy to like, chop off and release as CO2 later.

28 minutes 15 seconds

Do you see this right here?

28 minutes 17 seconds

COO, This looks like a good place to go break a bond, release CO2.

28 minutes 21 seconds

So we're, our cells are arranging these molecules to get prepared to broken down even further.

28 minutes 27 seconds

So we're gonna remove these phosphates off here, give them to ADP, and there's our first ATP back.

28 minutes 32 seconds

Now we're net neutral 'cause that's what we've invested.

28 minutes 36 seconds

And that enzyme, phosphoglycerokinase, is going to add another phosphate residue.

28 minutes 42 seconds

Actually, let's see, are we going to take him off glycerokinase?

28 minutes 46 seconds

He's phosphorylating ADP, that's why.

28 minutes 49 seconds

Yeah, so he's a kinase, phosphoglycerokinase.

28 minutes 51 seconds

He's not phosphorylating glycerate.

28 minutes 53 seconds

He's removing phosphates and adding in the back onto ADP to end up making three phosphoglycerate.

29 minutes

OK, not by phosphoglycerate, just single phosphoglycerate.

29 minutes 3 seconds

So he's taking those off 2, two of the two molecules and leaving this one right here.

29 minutes 7 seconds

And then phosphoglyceramutase.

29 minutes 9 seconds

This is just up swapping it around.

29 minutes 12 seconds

I'm swapping that phosphate up here to get this down here so I can steal the hydroxyl group and force a double bond over here.

29 minutes 21 seconds

So I'm going to convert this guy phosphoglycerate into phosphoenolpyruvate.

29 minutes 25 seconds

This is actually a really, really important three carbon intermediate that's present in lots of organisms.

29 minutes 30 seconds

Plants use this too.

29 minutes 32 seconds

This trio, sugar PEP, this is a good intermediate and lots of pathways, particularly if you're converting back and forth.

29 minutes 38 seconds

Pyruvate.

29 minutes 39 seconds

So enolace is gonna end up removing 2 water molecules.

29 minutes 42 seconds

So we're gonna remove an OH from right here and we're gonna have, let's see it.

29 minutes 49 seconds

We're gonna have an OH, we're gonna remove the phosphate and move it up here.

29 minutes 54 seconds

And we've done some swapping, all right, but we're going to lose 2 water molecules from here to make PEP.

30 minutes 1 second

So look at the conversion.

30 minutes 2 seconds

We've got chapter 2.

30 minutes 3 seconds

We lost an oh right here.

30 minutes 5 seconds

And we've got a phosphate, but we lost the hydrogen atom on the other side and forced a double bond.

30 minutes 10 seconds

And so you snuck out a water molecule and and created phosphoenopyruvate.

30 minutes 16 seconds

Now you're already almost pyruvate.

30 minutes 19 seconds

See, it's in the name, but it's still phosphorylated and as an enol.

30 minutes 23 seconds

And you have to get rid of that phosphorylation.

30 minutes 26 seconds

And so pyruvate kinase is going to take that phosphate off, add it to ADP.

30 minutes 31 seconds

Now you got ATP and there's no more phosphates left, which is great.

30 minutes 35 seconds

So not only are there no more phosphates left, we've set this molecule up to sort of be ready to start chopping off more bonds.

30 minutes 43 seconds

Like this is a great place to start right here at the end, right?

30 minutes 46 seconds

If, if breaking this down and releasing CO2 gas is your goal, this is what it looks like.

30 minutes 51 seconds

This is how you could possibly set up and do this.

30 minutes 54 seconds

OK, so now we've got pyruvate actually produced.

30 minutes 58 seconds

Now, when that little bit of ATP is being produced in the payout phase, you have to recognize that you have some enzymes just kind of hanging out in your cytoplasm that are regenerating ATP one at a time by picking up ADP, adenosine diphosphate in an inorganic phosphate and smooshing them together and making ATP.

31 minutes 21 seconds

That's a real slow process, but it's like the scavenger, you know, picking these up and building them as needed to recycle phosphates.

31 minutes 30 seconds

But this is that was not enough to keep you alive, OK.

31 minutes 33 seconds

And so this is not the bulk of the ATP you would produce from this.

31 minutes 36 seconds

And so this is done by something called substrate level phosphorylation, which is like low level, low turn out regulation.

31 minutes 43 seconds

And so this here's an example where this is happening.

31 minutes 46 seconds

We're removing this phosphate off of this phosphoglycerate up here and we're adding it on the ADP to produce ATP.

31 minutes 53 seconds

And so that's what phosphoglycero kinase's job is, take it off of this thing we're breaking down and put it back on the ATP.

31 minutes 59 seconds

It's still transferring a phosphate, which is why it's a kinase.

32 minutes 1 second

But these enzymes, they end up localizing ADP.

32 minutes 7 seconds

Notice it's only got 2 phosphates on it, and they take that phosphorylated substrate like this guy, and they cut that off and transfer it onto ATP and they just get to regenerate ATP molecules, OK?

32 minutes 19 seconds

So you get a little bit of that along the way, but not the bulk of it.

32 minutes 23 seconds

So substrate level phosphorylation is low level here and there, a couple of instances that happen in glycolysis and the citric acid cycle.

32 minutes 31 seconds

But the real payout comes at this very, very end that we're going to talk about in the next lecture, which is oxidative phosphorylation.

32 minutes 38 seconds

This is literally stealing electrons to drive the work of phosphorylating large quantities of ADP into ATP.

32 minutes 50 seconds

So that requires an electron transport chain, which is at the very end of this well into the mitochondria.

32 minutes 56 seconds

That's the last step where most of the business is happening.

32 minutes 59 seconds

So we've broken apart our sugar molecule 6 carbons into 3 carbon halves, and we've phosphorylated them to destabilize them and start shifting around bonds.

33 minutes 11 seconds

And then we remove the phosphate residues at the end because we want them back.

33 minutes 15 seconds

And now we've moved bonds around and stolen some electrons to produce two pyruvate molecules.

33 minutes 22 seconds

So every six carbon sugar is going to be broken down and converted immediately into two three carbon pyruvate molecules.

33 minutes 30 seconds

This is all happening in a cytosol, which means the enzymes necessary for this are floating around in the cytoplasm.

33 minutes 36 seconds

Pyruvate is then going to be transported across the mitochondrial membranes to the inside matrix of the mitochondrian.

33 minutes 44 seconds

And that's where we're going to find not only that pyruvate gets oxidized a little further, which means it's going to have some electrons stolen.

33 minutes 52 seconds

But then we see that the product from that is going to feed into the citric acid cycle, all of the enzymes of which are necessary necessarily housed inside the matrix of the mitochondrian.

34 minutes 4 seconds

And so pyruvates to get the pyruvate gets transported into the mitochondrium.

34 minutes 11 seconds

And some of these electrons that are produced or some of these electrons that are stolen and given to NAD to carry are probably also going to be transported into the mitochondran.

34 minutes 21 seconds

Mitochondrion is going to need those electrons at the end of the pathway.

34 minutes 26 seconds

And it's evolved to have exchangers in the two membranes that allow it to move things in and out that it needs.

34 minutes 33 seconds

So for example, if you're moving NADH into the mitochondria and using it, you have to then swap some NAD plus back out so that it can be used in the cytoplasm.

34 minutes 44 seconds

If you're making ATP in the mitochondria, you have to, when you send it out to be used, you have to swap in ADP in inorganic phosphate.

34 minutes 53 seconds

Otherwise you can't keep making more ATP.

34 minutes 55 seconds

So they're exchangers that will bring in what's needed for building and send out what you've already made.

35 minutes 1 second

OK.

35 minutes 1 second

And so we're gonna see that these next steps actually happen in the mitochondrial matrix.

35 minutes 6 seconds

If you remember a little bit about the anatomy of a mitochondria and you'll remember that it has a whole bunch of internal folds that are inside of it, Lots and lots and lots of surface area of membranes so that you can support a lot of electron transport chain protein complexes, So you can make tons of ATP.

35 minutes 27 seconds

And remember around those membranous folds is going to be fluid that's very similar to the cytoplasm in our cells, but would have been the cytoplasm in the bacterial cell that this evolved from.

35 minutes 39 seconds

And so now we call it matrix instead of cytoplasm.

35 minutes 43 seconds

But all the enzymes necessary for pyruvate oxidation chopping it down a little further and the citric acid cycle chopping it down the rest of the way are present in the matrix, OK.

35 minutes 54 seconds

And so after that, it's going to head what the what's produced out of the citric acid cycle is going to end up heading to these individual little Christae where the complexes necessary to produce ATP are going to be present.

36 minutes 9 seconds

So remember, anytime we see a whole lot of membranes, what we're really trying to do is increase surface area.

36 minutes 14 seconds

We're trying to do a whole lot of business, a whole lot of ATP production in a very small space because your cells demand it.

36 minutes 23 seconds

OK, so now we're inside the matrix in the mitochondrium, and we're going to see that pyruvate is going to be oxidized.

36 minutes 29 seconds

Now, don't let yourself get confused about redox terms.

36 minutes 32 seconds

I know that remembering reduction in oxidation can be really confusing.

36 minutes 37 seconds

Oxidation is electron theft.

36 minutes 37 seconds

Oxidation is electron theft.

36 minutes 40 seconds

OK.

36 minutes 41 seconds

Remember, the goal here is to take these carbon molecules and break them apart, to steal the electrons in their bonds, as well as the ones between the hydrogen atoms that are in some of them as well.

36 minutes 54 seconds

And so oxidation is breaking things down.

36 minutes 57 seconds

When you reduce something, you're giving it electrons, which means you're building it up, you're creating bonds.

37 minutes 2 seconds

And so after glycolysis, we're going to see pyruvate is going to be the next target, OK.

37 minutes 10 seconds

And so pyruvate is going to be transported across both membranes of the mitochondrion, the outer and inner membrane, and past the intermembrane space.

37 minutes 20 seconds

And it's going to end up going into the mitochondrial matrix, OK.

37 minutes 24 seconds

And so these Gray balls represent carbon atoms.

37 minutes 27 seconds

This is a simplified version of thinking about breaking down an organic thing, A3 carbon sugar, called a triose.

37 minutes 34 seconds

The enzymes necessary for doing it are present in the mitochondrial matrix.

37 minutes 38 seconds

And so remember that we've set up pyruvate to be ready to just chop off the end and that becomes our first CO2 that we can lose from every single pyruvate.

37 minutes 50 seconds

We're going to do this to both of the pyruvates that came out of the glycolysis.

37 minutes 53 seconds

So if we cut this bond right here and we steal the two electrons and we give them to NAD plus, it will become NADH.

38 minutes 1 second

And we've managed to release this CO2 into the matrix.

38 minutes 8 seconds

It'll diffuse out of the mitochondria, out of our cell, into our bloodstream, out of our lungs.

38 minutes 13 seconds

We get rid of it as waste.

38 minutes 15 seconds

And then what we do is we take a placeholder to satisfy this poor carbon.

38 minutes 19 seconds

Because if we break this bond and steal the electrons between the red carbon and the black one, this black carbon does not have a fourth bond like it's supposed to.

38 minutes 27 seconds

So it's not going to be happy.

38 minutes 28 seconds

It's going to be reactive.

38 minutes 29 seconds

And so we go whoop and we put in a placeholder that's called Coenzyme A.

38 minutes 35 seconds

So coenzyme A is going to be this COA molecule attached to a sulf hydro group.

38 minutes 42 seconds

And by taking that hydrogen off, it's easy to attach the sulf hydro group to acetyl COA.

38 minutes 47 seconds

It's just a handle a placeholder to keep this carbon happy because now we've got to go.

38 minutes 53 seconds

I got to get rid of this one and I got to get rid of that one.

38 minutes 55 seconds

And then I've broken apart all the carbons that I started with initially.

38 minutes 58 seconds

So this very first step is going to convert A3 carbon pyruvate into two carbon acetyl COA, right?

39 minutes 6 seconds

It's an acetyl group here.

39 minutes 8 seconds

This carbonyl and methyl is an acetyl group attached to coenzyme A as a placeholder.

39 minutes 15 seconds

OK, so we've stolen a couple of electrons by breaking a bond and given them to NAD plus to make NADH.

39 minutes 22 seconds

And we've released a carbon atom.

39 minutes 23 seconds

So we're going to get 2 molecules of NADH from these two pyruvates and we're going to get 2 molecules of CO2 released from these two pyruvates.

39 minutes 30 seconds

OK, not too, not too difficult.

39 minutes 33 seconds

We're skimming, right?

39 minutes 34 seconds

We're skimming electrons off wherever we can as we're breaking this thing down.

39 minutes 39 seconds

And so acetyl COA is this molecule here, an acetyl group with a COA.

39 minutes 43 seconds

And the first thing that's going to happen is we're going to get rid of that COA.

39 minutes 46 seconds

It's just a placeholder, like a bookmark, OK.

39 minutes 49 seconds

And so this is giving you an example of what this looks like.

39 minutes 52 seconds

And COA is actually quite large coenzyme AI don't guess, I don't need to go into details about this, but you can see there's a bunch of phosphate residues in it.

40 minutes 1 second

It's looks like there's a purine base at the end of it.

40 minutes 5 seconds

But the part we want that we're going to use is this part right here, this acetyl group.

40 minutes 10 seconds

So it's got a methyl and a carbonyl and that's it.

40 minutes 14 seconds

This is just a placeholder that gets recycled and reused.

40 minutes 17 seconds

Throughout the cell, but it gets added on to this part.

40 minutes 21 seconds

OK.

40 minutes 22 seconds

All right.

40 minutes 23 seconds

So the third step of glucose oxidation, breaking down glucose molecules.

40 minutes 28 seconds

And I guess when I talk about it happening in three steps, the actual breaking apart of glucose happens in three steps, glycolysis, pyruvate oxidation, citric acid cycle.

40 minutes 39 seconds

The fourth major step is where all the business of making ATP happens.

40 minutes 43 seconds

But by then glucose is gone.

40 minutes 45 seconds

OK, Remember that after glycolysis, the majority of the energy is stored in pyruvate.

40 minutes 53 seconds

And then you start to see that there's some energy left in acetyl COA, but you're losing bits of it by breaking bonds and skimming off electrons.

41 minutes

And so acetyl COA is going to be fed into this pathway.

41 minutes 4 seconds

This the cycle called the citric acid cycle.

41 minutes 7 seconds

It's got a few names.

41 minutes 8 seconds

Sometimes it's called the TCA cycle, but citric acid is an intermediate molecule or intermediate metabolite that's in this cycle and one of the first that was probably identified, which is why it's called this.

41 minutes 19 seconds

And so the goal here is to take those two additional carbons and break them apart and get rid of them and then try to skim as many electrons as we can off of this cycle because we need them at the last step to be able to produce ATP.

41 minutes 33 seconds

Remember, electrons are energetic.

41 minutes 34 seconds

They'll do work.

41 minutes 35 seconds

If we pass them around from neighbor to neighbor, everybody does some work.

41 minutes 39 seconds

OK, So acetyl COA is going to end up being oxidized.

41 minutes 42 seconds

We're going to break the bonds here and steal their electrons and hand out these carbons as CO2 gas.

41 minutes 49 seconds

OK, so I'm going to take you stepwise through the citric acid cycle.

41 minutes 53 seconds

And I don't want you to get scared when you see the molecules.

41 minutes 56 seconds

I just want you to start watching as things move around as, as, as intermediate metabolites that are worked on at every step by enzymes, just like the other enzyme pathways, the metabolic pathways I showed you.

42 minutes 11 seconds

So the later when you see this, you're not like really scared by all the intermediates and the chemicals that you can look like it's a puzzle and see exactly where things move to understand what happened and how it got back to where you started.

42 minutes 24 seconds

Very similar to Calvin's cycle.

42 minutes 26 seconds

Part way through this, you're basically almost done.

42 minutes 28 seconds

Then you just have to recycle it all back to where you started.

42 minutes 31 seconds

If you don't, the cycle falls apart.

42 minutes 33 seconds

OK.

42 minutes 34 seconds

And so some of the potential energy that is released from acetyl COA is going to be used for these purposes.

42 minutes 40 seconds

We're going to break some more bonds and hand those electrons off to NAD plus who's our carrier?

42 minutes 45 seconds

And he's going to become reduced to to be NADH.

42 minutes 47 seconds

Remember, every NADH is hiding 2 electrons and got one extra proton and it's going to go deliver those electrons to the electron transport chain, hence the name.

42 minutes 58 seconds

And then we're also going to see his cousin FAD is going to be reduced also.

43 minutes 4 seconds

This is another electron carrier that gets made at the other end of the pathway.

43 minutes 8 seconds

It's carrying two electrons also, but it's already, it doesn't have a positive charge on it.

43 minutes 13 seconds

So if you give it two electrons, you got to give it two protons and it becomes a stable molecule called FADH, flavin adenine dinucleotide.

43 minutes 22 seconds

It's going to take its electrons to the electron train, transport train also, but it hands them off only to one special complex.

43 minutes 28 seconds

And I'll tell you about that in the next lecture.

43 minutes 31 seconds

And then one of the other little skimming activities we get off of here, I know the image shows ATP, but ultimately that gets converted into something called GTP or GTP happens 1st and gets converted into ATP.

43 minutes 44 seconds

Whatever you're, you're stealing phosphates back again to make an energetic molecule, right?

43 minutes 48 seconds

So there's a little bit of that.

43 minutes 50 seconds

And this isn't done intentionally to make ATP.

43 minutes 53 seconds

So we live.

43 minutes 54 seconds

This is because you're using a phosphate temporarily for a job and then handing it back off to ADP.

44 minutes

This is just, you know, for the sake of chemistry.

44 minutes 3 seconds

OK, All right, now we're going to walk stepwise through this.

44 minutes 5 seconds

Don't get scared.

44 minutes 6 seconds

It's not going to kill you.

44 minutes 7 seconds

But I want you to keep track of the colored carbon atoms.

44 minutes 11 seconds

The ones you come in with are not necessarily the same as the ones that get kicked out of this pathway.

44 minutes 18 seconds

OK.

44 minutes 19 seconds

So here we've got acetyl, COA acetyl, and the acetyl group is just a carbonyl and a methyl, right?

44 minutes 25 seconds

Chapter 3 and C 11 and O, and it's going to be attached to this COA coenzyme A.

44 minutes 32 seconds

The bulk of this is going to be added on to the first intermediate in the citric acid cycle that becomes like a holder or a carrier, and it's called oxaloacetate.

44 minutes 44 seconds

We're going to swap out the COA and there's an enzyme that does this.

44 minutes 48 seconds

I've taken away the enzymes so that it's not super confusing.

44 minutes 51 seconds

There's an enzyme that takes off the COA and adds the rest of this on to oxaloacetate.

44 minutes 57 seconds

And you can see by losing this double bond right here with oxygen and making it a single bond, giving oxygen a, a hydrogen atom, we can add on acetyl COA and this carbon is happy.

45 minutes 10 seconds

Everybody's happy.

45 minutes 11 seconds

They all have enough, all the carbons have enough bonds and now what you've created is 123456 carbon sugar.

45 minutes 20 seconds

You took a four carbon, you added two, and you created A6 carbon intermediate.

45 minutes 24 seconds

And citrate is actually used in many places as a source of energy and many metabolic pathways.

45 minutes 31 seconds

And so start paying attention to the colors.

45 minutes 33 seconds

Here are the red carbons that we added.

45 minutes 35 seconds

Here are the blue ones.

45 minutes 36 seconds

These are the ones that are going to end up going.

45 minutes 39 seconds

They're going to leave.

45 minutes 40 seconds

Notice why this is already set up as CO2 Break that bond and it's gone.

45 minutes 46 seconds

It goes away as gas.

45 minutes 47 seconds

Same thing with this one.

45 minutes 49 seconds

This is already set up as CO2 Cut that bond off and you release it as the CO2 molecule.

45 minutes 54 seconds

No problem.

45 minutes 55 seconds

And so in our first steps, we're just going to start rearranging things.

45 minutes 59 seconds

You're going to see that a lot of metabolic pathways of chemistry is you move here, you move there.

46 minutes 4 seconds

It's like a Rubik's Cube where you're trying to rearrange the colors of the shapes to get to the part you want.

46 minutes 9 seconds

And so by using water and then taking it back out again, we're literally just swapping a hydroxyl group from here to here.

46 minutes 17 seconds

And we've taken off one hydrogen from this carbon and given this one a hydrogen instead.

46 minutes 22 seconds

Do you see how you're kind of swapping?

46 minutes 24 seconds

We've converted it from citrate into ISO citrate.

46 minutes 26 seconds

OK, So we're just kind of swapping around.

46 minutes 29 seconds

All right, So follow the arrows and see what happens.

46 minutes 33 seconds

Now ISO citrate is going to get converted into something called alpha ketoglutarate.

46 minutes 38 seconds

And what's going to occur is we're going to break some bonds, OK?

46 minutes 43 seconds

So see how NAD is involved here.

46 minutes 45 seconds

We're going to steal some electrons and hand it off to NAD.

46 minutes 48 seconds

So it becomes NADH and we're going to release 1 carbon dioxide molecule.

46 minutes 55 seconds

Now let's count where it happens from.

46 minutes 57 seconds

So carbon, red carbon's the same.

46 minutes 59 seconds

Black carbon.

47 minutes

Look at this.

47 minutes 1 second

This one gets cut off and disappears.

47 minutes 4 seconds

We break this bond, we steal those two electrons and we hand them to NADH, to NAD Plus, and it becomes NADH.

47 minutes 11 seconds

And remember for every single sugar molecule, there's two of these acetyl coase going through the citric acid cycle.

47 minutes 17 seconds

So you're going to end up with two NADH.

47 minutes 20 seconds

And by cutting this off, it's already in the form of COO CO2 break this bond, now it's CO2 gas and it goes away.

47 minutes 28 seconds

And so that's the 1st place where we release this.

47 minutes 30 seconds

And now you've got A5 carbon intermediate called alpha ketoglutarate, OK?

47 minutes 36 seconds

And so the next thing that is going to be different here is you're also rearranging this hydrogen atom is gonna be taken off.

47 minutes 44 seconds

That's where this comes from.

47 minutes 46 seconds

And because you took it away and you're gonna take this one away, take two of them, This has to double bond with oxygen 'cause otherwise oxygen's not happy and carbon's not happy, which is why this now looks like it's double bonded.

47 minutes 58 seconds

OK, which do you think is the next CO2 that's gonna be cut off this molecule?

48 minutes 5 seconds

Probably the blue guy here at the bottom right.

48 minutes 7 seconds

He's lined up and ready to go.

48 minutes 9 seconds

If we break this bond, we steal the two electrons out of it, and we find a way to satisfy carbon.

48 minutes 14 seconds

We can release this as CO2 gas.

48 minutes 17 seconds

And that's exactly what's going to happen.

48 minutes 19 seconds

So this is gonna end up being cut off by an enzyme and released as CO2 gas, but now you have to satisfy this carbon.

48 minutes 29 seconds

So we're gonna steal the electrons that are in the bond, and we're gonna give it 1080 plus, OK, and we're going to make NADH with it.

48 minutes 39 seconds

But we have to swap in a placeholder because otherwise carbon is missing a fourth bond.

48 minutes 43 seconds

And COA Coenzyme A is a good placeholder.

48 minutes 46 seconds

It's clearly floating around in the matrix to be used.

48 minutes 49 seconds

So we're going to transfer Coenzyme A onto the end of this carbon, and now it's got four bonds and it's happy.

48 minutes 55 seconds

But we have managed to take its electrons, and we took this hydrogen atom right off of COA, and that's where that came from.

49 minutes 3 seconds

And so we're going to do this twice.

49 minutes 4 seconds

We're going to get 2 NADH produced here simply by swapping off this carbon and stealing the electrons that broke the bond and then going, OK, satisfy this guy by putting on a succinal A, a coenzyme.

49 minutes 17 seconds

And then we'll take the coenzyme back.

49 minutes 18 seconds

We'll swap it out with something else so that we can start converting it back to where it's supposed to be.

49 minutes 24 seconds

All right, the next step, so that converts alpha ketogliterate into succinyl COA.

49 minutes 30 seconds

And if we take off the COA, succinyl COA becomes just succinate.

49 minutes 33 seconds

OK, simple way of converting it to A4 carbon intermediate that's now making its way back to regenerating oxaloacetate.

49 minutes 42 seconds

Now this looks kind of messy, but what happens here in this process, in order to steal this COA back and convert this group down here from a carbonyl to a carboxyl, we need to have a ready oxygen to give this group.

49 minutes 59 seconds

And the easiest way to do that 'cause they're always floating around is use inorganic phosphate, which is just PO4 floating around in inside the matrix.

50 minutes 9 seconds

And so an enzyme is gonna swap off this COA and add on an inorganic phosphate that looks like this right here.

50 minutes 18 seconds

And so it's going to add one of these at the oxygen to this carbon.

50 minutes 21 seconds

And now it went from a carbonyl to a carboxyl.

50 minutes 26 seconds

What happened to do that is we added the phosphate and then took almost all of it back.

50 minutes 33 seconds

If you add on a phosphate PO4, OK, to the end of this, but then you take back PO3 and you add it on to an ADP, you can leave behind one oxygen atom.

50 minutes 45 seconds

And so you end up with COO.

50 minutes 46 seconds

And so that's all it's doing.

50 minutes 50 seconds

It's swapping out the succinyl COA.

50 minutes 52 seconds

Instead of adding to something plain like an H, it needs to convert back into COO because notice how many of those are in these molecules.

51 minutes 1 second

You're trying to get it back to the original COO that's present at the beginning of this pathway.

51 minutes 7 seconds

And so you've managed to convert this back.

51 minutes 9 seconds

So now you've got a carboxyl group, you've got like 2 carbons in the middle that are saturated and another carboxyl group.

51 minutes 16 seconds

So we're realigning our molecule to then rearrange it to back to oxaloacetate.

51 minutes 21 seconds

And so we steal back most of that phosphate and we make one molecule of ATP.

51 minutes 25 seconds

It's not because we're trying to produce energy at this step.

51 minutes 29 seconds

It's 'cause you used a phosphate as a placeholder, cut most of it back off and left an O behind and then regenerated ATP from it.

51 minutes 36 seconds

OK, Succinate is gonna be converted into fumarate, which is the next intermediate metabolite.

51 minutes 43 seconds

And what's gonna happen is we're gonna steal electrons by removing some HS.

51 minutes 50 seconds

Look what happens here.

51 minutes 52 seconds

This H right here is going to be taken off of this carbon, and it's going to be added on to FAD.

52 minutes 1 second

And this H right here, one of those is going to be taken off and added to FAD.

52 minutes 7 seconds

And so that makes them FAD H2.

52 minutes 10 seconds

And then look what happens in Fumarate.

52 minutes 13 seconds

He lost AH, and he lost an H.

52 minutes 16 seconds

So they had to double bond between each other in order to be satisfied.

52 minutes 19 seconds

Remember, carbon has to make 4 bonds always.

52 minutes 21 seconds

So if you steal one hydrogen from here and one hydrogen from here, these two have to double bond.

52 minutes 27 seconds

But you can now take those electrons and hand them off to your electron carrier and you have converted succinate into fumarate.

52 minutes 34 seconds

OK?

52 minutes 35 seconds

Now fumarate is going to be converted into malate.

52 minutes 38 seconds

We need to get rid of this double bond, and we're going to use water to help us do that.

52 minutes 42 seconds

OK, so look what happens.

52 minutes 44 seconds

We've got chapter and chapter.

52 minutes 46 seconds

We're going to use a water molecule and we're going to give the OH to the carbon on the top and the other H to the carbon on the bottom.

52 minutes 53 seconds

OK.

52 minutes 54 seconds

So that's all we're doing is we're making sure that they're happy and satisfied and that they don't have double bonds between the carbons.

53 minutes

It's OK.

53 minutes 1 second

We want to get back to just this double bond up here.

53 minutes 4 seconds

And so then malate is going to be converted into oxyloacetate.

53 minutes 8 seconds

And now we're back where we started.

53 minutes 10 seconds

And the way that that happens is we're going to use, we're going to, we're going to remove some electrons here and we're going to give them to NAD Plus.

53 minutes 21 seconds

All right, So what are we removing?

53 minutes 24 seconds

Well, we're going to sort of rearrange these.

53 minutes 26 seconds

This carbon on this side is going to end up this guy.

53 minutes 31 seconds

We're making the different shape, making it AT shape.

53 minutes 33 seconds

This carbon right here is going to be this guy in the middle.

53 minutes 37 seconds

And we're going to take away some of these hydrogens.

53 minutes 40 seconds

We're going to take both of these hydrogen atoms off and force this to double bond.

53 minutes 45 seconds

The Chapter 2 is the same and the carboxyl's the same.

53 minutes 48 seconds

And so we're stripping away these oxygens and we're handing them or these hydrogen atoms, I'm sorry, we're handing their electrons off to NAD.

53 minutes 55 seconds

Plus what's left is its protons.

53 minutes 56 seconds

And now we've got NADH and we're going to do get two of those.

53 minutes 59 seconds

So we've got two NADH, one CO2 released, the 2nd CO2 released, CO2's done, no more carbons left in the molecule.

54 minutes 7 seconds

And then we've got two more NADH.

54 minutes 10 seconds

We've got two ATP, two FADH, two, and two more NADH.

54 minutes 15 seconds

And so how many electrons is that total?

54 minutes 17 seconds

Well, if every NADH is carrying two, we've got 246810121416.

54 minutes 28 seconds

We got 16 electrons coming out of the citric acid cycle that will all be sent over to the electron transport chain to do the work of making ATP.

54 minutes 38 seconds

So this is a good pathway for scavenging electrons and sending them over like fuel to the electron transport chain.

54 minutes 46 seconds

All right.

54 minutes 47 seconds

And so this is a summary that takes away the actual structures of the molecules, but it does help you to look and see what bonds have changed.

54 minutes 54 seconds

And then as you look at other chemical processes and biochemical processes, they're not so scary if you just realize that each enzyme is making one minor change and you get to a point in the cycle where everything's got to go back to what you started with.

55 minutes 6 seconds

Otherwise the cycle won't continue.

55 minutes 8 seconds

And so citric acid cycle is the end step.

55 minutes 11 seconds

It completes the rest of glucose oxidation.

55 minutes 14 seconds

We went from six carbons to two threes.

55 minutes 16 seconds

We went from 2 threes to two twos, and then we went from 2 twos to none.

55 minutes 21 seconds

And we broke in all the bonds and still so in all the electrons we possibly can.

55 minutes 26 seconds

And so the energy that comes out of that oxidation of an acetyl COA molecule, just one of them, which is half a sugar, you get 3 NA, DH1F, Ed, H2, and one GTP, which ultimately is converted into ATP.

55 minutes 39 seconds

And so in total, from 1 sugar molecule, you're going to get 6 NADH.

55 minutes 43 seconds

Just from citric acid, you're going to get 2FA D, H2, and you're going to get 2 GTP.

55 minutes 50 seconds

And so those guys are really important.

55 minutes 52 seconds

The carriers, they're going to take those electrons that were stolen out of the bonds of sugar, and they're going to send them over to the electron transport chain where they're going to be used in a special process to produce ATP.

56 minutes 4 seconds

And you've managed to release your CO2 as waste.

56 minutes 9 seconds

OK, now we look at this and we go, well, that's a lot of business, whole lot of things happen, lots and lots of electrons, not a lot of ATP yet though, right?

56 minutes 18 seconds

So glucose oxidation really is the payout of it is just getting all the electrons.

56 minutes 25 seconds

You only get like a couple ATP molecules, nothing really crazy, right?

56 minutes 29 seconds

And so every single glucose molecule that's gonna be oxidized, it's gonna be oxidized down into 6 carbon dioxides.

56 minutes 37 seconds

OK, six carbons, 6 carbon dioxides are gonna be released, right?

56 minutes 41 seconds

You break 6 into two halves, you get 2 threes, 123456.

56 minutes 46 seconds

They're all gonna be released as carbon dioxide gas.

56 minutes 49 seconds

And so by reducing by by oxidizing the sugar, you end up taking those electrons and reducing NAD plus to NADH.

56 minutes 58 seconds

And so you end up reducing in total through the whole process, 10 molecules of NAD plus to 10 molecules of NADH.

57 minutes 5 seconds

Remember, all the HS are hiding, there's two electrons hiding in each of these.

57 minutes 8 seconds

So that's 20 electrons.

57 minutes 10 seconds

In NADH you get 2 molecules of FAD reduced to FAD H2, right?

57 minutes 16 seconds

And each one of these is holding two electrons.

57 minutes 18 seconds

So that's four more electrons.

57 minutes 20 seconds

OK, so that's 24 electrons, and then you're gonna get a total of 4 molecules of ATP.

57 minutes 26 seconds

So remember, you had an investment phase at the top where you invested 2, but then you got those two back, +2 more plus two more.

57 minutes 35 seconds

So really you're only totaling 4 molecules of ATP.

57 minutes 38 seconds

Now if you think 4 molecules of ATP is enough to keep you alive, you're sorely mistaken.

57 minutes 43 seconds

And so it's very clear that this is not where all the ATP is produced, that that must be the end payout.

57 minutes 50 seconds

Even Homer's kind of confused with all the ATP, but you did get all the energy in the form of the electrons you've harvested them.

57 minutes 57 seconds

OK, so this portion in white here is the glycolysis part.

58 minutes 1 second

The pyruvate processing is the little skinny part here.

58 minutes 3 seconds

And then the citric acid cycle is really where the electron payout is.

58 minutes 7 seconds

Look, NADHNADHNADHFAD, H2, NADH, that's where all the electrons are coming out in the citric acid cycle.

58 minutes 14 seconds

And so notice the interesting way this is graphed also, this is the free energy change relative to glucose, as glucose is oxidized as a function of the process of oxidizing it.

58 minutes 30 seconds

Sorry about that.

58 minutes 31 seconds

So here we've got free energy, right?

58 minutes 34 seconds

Remember that in an exergonic process like this, the delta G that's given off should be negative.

58 minutes 42 seconds

And notice that as you progress through the stages of glucose oxidation, that's what you get.

58 minutes 49 seconds

You're getting more and more negative free energy.

58 minutes 53 seconds

So there's a lot of free energy -700 kilocals per mole, a lot of free energy that's being released from this molecule.

59 minutes 2 seconds

The negative delta G is good.

59 minutes 4 seconds

That's an exergonic reaction, giving off energy that's gonna, in this case, we're harnessing that in the form of electrons to go do additional work for us as we oxidize glucose, right?

59 minutes 16 seconds

There's nothing left.

59 minutes 17 seconds

By the time we get all the way through the citric acid cycle, everything has been stripped out in the form of electrons.

59 minutes 22 seconds

And it's really fascinating to see what they're gonna do next.

59 minutes 25 seconds

And you're gonna see that the next time we talk.

59 minutes 28 seconds

Thank you so much for your attention.

59 minutes 29 seconds

I really do hope that cellular respiration doesn't scare you.

59 minutes 32 seconds

It's very challenging to learn the first time because you start to lose the understanding through the molecules, right?

59 minutes 38 seconds

You look at a lot of carbons and HS and oxygens, and it gets really confusing.

59 minutes 42 seconds

But if you just understand what's moving around where, and you'd ignore the enzymes for a little while until you know they need to be put back into the process.

59 minutes 51 seconds

But recognize the point of each step.

59 minutes 54 seconds

The breaking of glucose, making it unstable, trapping it in the cell first so it can't leave.

59 minutes 59 seconds

Making sure that the grading of glucose always looks low in the cell by converting it into something else and then unstabilizing it and breaking it apart.

1 hour 7 seconds

And chopping, chopping, chopping, stealing the electrons from the bonds, releasing CO2 as waste, and giving those electrons over to the carriers, the electron carriers who will transport them to the electron transport chain.

1 hour 19 seconds

So don't lose the forest through the trees.

1 hour 21 seconds

Don't focus too hard on the molecules.

1 hour 22 seconds

I'm not going to make you draw those.

1 hour 24 seconds

I just want you to understand what's happening in this process.

1 hour 27 seconds

This is a huge process that if anything causes it to cease, it can very quickly lead to death.

1 hour 35 seconds

And so it's very important to have a strong foundation in cellular respiration.

1 hour 38 seconds

After all, everything you do, every step you take, every electron you break, every bond you break is is done to support cellular respiration.

1 hour 49 seconds

All right, until next time, I hope you have a wonderful day and you'll be hearing from me again very soon.