Welcome to tutorial 28. Our topic today is carbohydrate metabolism and we will be placing a special emphasis on the catabolic process known as glycolysis. Before we get started just a quick reminder that the notes to accompany this video tutorial are available online through my website and with that said let's get started first. with an overview of carbohydrate metabolism. So we already know that the carbohydrates from our diet are digested and in that digestion process the glycosidic bonds in the polysaccharides and disaccharides are hydrolyzed freeing up the monosaccharides which can then be absorbed into our bloodstream.
Now the primary monosaccharide from the digestion of carbohydrates is glucose. So I'm going to write up here carbs from our diet. We already know that they undergo a whole lot of hydrolysis in the digestion process. freeing up the monosaccharides again primarily the monosaccharide that's freed up from digestion of our carbohydrates is glucose so i'm going to go ahead and write glucose here because that's really what we're going to focus on today is the metabolism of glucose and then glucose that six carbon molecule of glucose is broken down in catabolism through a 10-step process known as glycolysis it gets broken down into two separate three carbon molecules of pyruvate.
So I'm going to write pyruvate here and that's through the ten steps of glycolysis. Pyruvate is then oxidized into the two carbons of the acetyl portion of acetyl coenzyme A. And remember that pyruvate is a three-carbon molecule. The acetyl group is only two carbons.
One of those carbons is going to be fully oxidized in pyruvate oxidation into carbon dioxide. So I'm going to write a CO2 coming off here during pyruvate oxidation. And from here, we're already familiar with what can happen in complete catabolism. We talked about it in tutorial number 27. We know that the two carbons from the foods that we eat, which have been broken down into the acetyl portion of acetyl coenzyme A, can enter into the Krebs cycle. Where they are ultimately oxidized all the way to carbon dioxide.
Alright, CO2 here. We know that in the Krebs cycle, we get GTP, guanosine triphosphate, very similar to ATP. And because we have oxidation steps here, we know that these oxidation steps are going to be coupled to the reduction of some coenzymes. So in one turn of the Krebs cycle, we get three reduced coenzymes of NADH.
and one reduced coenzyme of FADH2, which are then going to be reoxidized via the electron transport chain. I'm going to write E. T, C for electron transport chain.
And ultimately, the electrons and hydrogen ions are going to be passed to oxygen from the air that we breathe, reducing the oxygen from the air that we breathe. it to water. Okay, so I'm gonna write right here in a blue pen I think, make it stand out a little bit. The ultimate acceptor of those electrons and hydrogen ions in the electron transport chain, the ultimate acceptor is oxygen from the air that we breathe, and in that highly exergonic process, of creating the H2O from the oxygen, in that highly exergonic process, the energy is harnessed to power oxidative phosphorylation.
Okay, so I'm going to write slash ox-ph for oxidative phosphorylation, which is simply the phosphorylation of ADP into ATP. So let's write that over here. energy harnessed from the electron transport chain is used to phosphorylate ADP into ATP.
And the result of that process is that these reduced coenzymes have been reoxidized. So let's write 3 NAD plus down here and 1 FAD. Okay. Alright, so when the cells are in need of energy, this catabolic process is occurring.
But what happens when the cells have plenty of energy and glucose is in excess amounts? Well excess glucose... will be stored as glycogen primarily in the muscles and liver. And this anabolic process, the synthesis of glycogen for storage of glucose, is known as glycogenesis. And then that glycogen can be broken down at a later time back into glucose through the process known as glycogenolysis.
Okay, so if you're thinking, those terms all sound really similar. Glycolysis, glycogenesis, glycogenolysis, they do sound very similar. And that's kind of why I like to point out these other pathways here, so that you are sure not to confuse these different terms.
Remember that the term lysis means the breakdown or decomposition. And remember that genesis means the creation of, the synthesis of. Okay, so that should make it easier for you to remember what these three terms, which may otherwise sound very similar, what these three terms mean. Glycolysis is the breakdown of glucose.
okay breaking it down into pyruvate. Glycogenesis is the synthesis of glycogen from glucose. Glycogenolysis is the breakdown of glycogen to free up glucose when energy is needed again by the cells.
Now another pathway that can be taken when cells have adequate energy is that acetyl coenzyme A can be used to synthesize fatty acids which can then be used to synthesize triglycerides which go into our fat cells for a longer-term storage. This is the process of lipogenesis. Or the synthesis of lipids. So we start to see sort of a relationship between carbohydrates that we eat and the storage of fats.
We knew it... could happen. We knew that if we ate too many carbs that the excess carbs could be stored as fat.
So now we actually see where that pathway comes from. Alright, so again just an overview of carbohydrate metabolism We will be focusing on the catabolic processes Not these anabolic processes of building up these larger molecules But again, I like to show it as part of the overview and since we We already talked about, let's use the red pin here, since we already talked about the Krebs cycle, the electron transport chain, and oxidative phosphorylation in great detail in Tutorial 27, we actually don't need to... talk about these catabolic processes in great detail today, that means that for today we will be focusing exclusively on the catabolic processes of glycolysis and pyruvate oxidation.
So I'm going to write focus for today. Alright, so with that said, let's go ahead and go on to slide number two and start talking in more detail about that 10-step process of glycolysis. Okay, so we're going to start out with an overview.
of glycolysis because I think it can be very overwhelming to start out by looking at the 10-step process directly. So starting out with just an overview first of what's happening in this process? Well first of all glycolysis occurs within the cytosol of our cells and then the product of glycolysis, the pyruvate, is then taken into the mitochondrial matrix and it's within the mitochondria that the remainder of the catabolism occurs. Okay so let's write up here first. Occurs within the cytosol of cells.
We already said that glycolysis is a 10-step process and all that's happening overall in this process is that the six carbons of glucose are being broken apart into two three carbon molecules of pyruvate. So let's write that up here. Glycolysis is a ten step process in which the six carbons And we can really separate this process into the first half and the second half. So in the first half of glycolysis, that would be steps one through five. All that's happening in those steps.
is that the six carbons of glucose are being cleaved apart into two three-carbon molecules of D-glyceraldehyde 3-phosphate. Not pyruvate yet, because we're just talking about the first five steps. Okay, so let's write here. Steps one through five. Glucose is cleaved.
And then in the second half, so that's steps 6 through 10, all that's happening overall in those steps is that those two 3-carbon molecules of D-glyceraldehyde 3-phosphate, they're just being converted all the way into pyruvate. Okay, so I'm going to write here, steps 6 through 10, the 2-3-carbon. molecules of d-glyceraldehyde 3-phosphate.
I'm going to abbreviate G3P just to save myself a little time. DG3P, that stands for the D-glyceraldehyde 3-phosphate. So those two 3-carbon molecules of D-glyceraldehyde 3-phosphate are converted. That's an N. Converted to two 3-carbon molecules.
of pyruvate. Okay, so an important note here is that step 6 through 10 is going to actually happen twice because it's going to happen once for the first D-glyceraldehyde 3-phosphate unit, and then it's going to happen once for the second D-glyceraldehyde 3-phosphate unit. again a second time for the second D-glyceraldehyde 3-phosphate molecule. Okay, so step 6 through 10 actually happen two times, once for each D-glyceraldehyde 3-phosphate that was formed in steps 1 through 5. So let me write here, this happens twice. Once for each D-glyceraldehyde 3-phosphate molecule.
Okay, exclamation mark. All right, and that's it. Overall, that's all that's happening in the process of glycolysis.
Okay, so let's go ahead and zoom in to the reactions that we have on slide 3. And as we look at those reactions, we'll talk a little bit more about the details of each of those steps. Okay, so here we are zoomed in to slide three, looking at the details of the process known as glycolysis. So, we're going to start with the glycolysis. Remember, we already talked about the overview.
Overall, all that's happening in the process of glycolysis is that the six carbons of glucose are being broken down into two separate three-carbon molecules of pyruvate. Okay, overall, that's all that's happening. So now we're going to look at the details of how that happens. Now just real quick before we get started, we are focusing on glucose here, the breakdown of glucose, but it's important to know that other monosaccharides from carbohydrate digestion like fructose, for example, would enter this pathway at different steps.
Primarily other monosaccharides will enter as either glucose 6-phosphate, so it'll be converted into glucose 6-phosphate, or as fructose 6-phosphate. So they'll enter this pathway as well. All right, so what's happening on step one? On step one, Our glucose molecule gets phosphorylated and the phosphate comes from ATP.
And so we're actually down one ATP just to start the process of glycolysis. The glucose 6-phosphate that results then undergoes an isomerization reaction forming the isomer fructose 6-phosphate. Step 3 is another phosphorylation.
Again, the phosphate comes from ATP, so we can see now that we're minus 2 ATP, just to start this process of glycolysis. And the product of that second phosphorylation, you'll see, is a molecule that's starting to look kind of symmetrical. And that makes sense, because what we want to do next in step 4 is cleave that molecule in half, making 2, 3 carbon molecules. each with one phosphate.
Okay, so these are going to be isomers. So on step four, we make these two isomers. We cleave that molecule and make two isomers, dihydroxyacetone phosphate and the deglyceraldehyde 3-phosphate. Now step five only happens for the dihydroxyacetone phosphate isomer. It is isomerized into the second molecule of deglyceraldehyde 3-phosphate, and it's only D-glyceraldehyde 3-phosphate that can continue through the pathway of glycolysis.
So little bit confusing, notice my step 6, we go all the way back up here okay, so I've drawn D-glyceraldehyde 3-phosphate and remember that step 6 through 10 will occur twice. Once for the first D-glyceraldehyde 3-phosphate molecule And again for the second, D-glyceraldehyde 3-phosphate. From one glucose, we get two D-glyceraldehyde 3-phosphates, which means we get step 6 through 10 happening twice, once for each D-glyceraldehyde 3-phosphate. That's very important. All right, step 6 is an oxidation of the aldehyde here into a carboxylic acid, which is then phosphorylated with inorganic phosphate, not ATP.
So this does not require ATP even though it's a phosphorylation. Because the substrate got oxidized, a coenzyme gets reduced. So we see a reduced coenzyme here.
In fact, I'm going to underline that because we know that's going to be important because that's going to get reoxidized later on in the electron transport chain and it's going to power oxidative phosphorylation. The next step, we can see that we transfer that phosphate to ADP, making an ATP. So we actually got an ATP back here.
Step eight of glycolysis. is just an isomerization. So the phosphate is now rearranged to this position here, which sets you up for step 9, which is a dehydration. We lose the alcohol and hydrogen as H2O.
creating a double bond here. And last but not least, we transfer the last phosphate to another ADP to make another ATP. So we got our ATP back, didn't we?
We had to invest some in the first half, but we got got some back in the second half, and the result is pyruvate, the three carbon molecule, one, two, three, pyruvate. All right, so overall, just do a quick summary of where the ATP is lost and gained in this process of glycolysis. Remember that we are minus two ATP. To start the process of glycolysis, the first half of glycolysis requires 2 ATP to get it going. So minus 2 ATP to start.
We used up 2 ATP to get this process going. But in the second half, we get 2 ATP. However, this process happens twice. Don't forget that.
We make two D-glyceraldehyde glyceraldehyde 3-phosphate molecules and each one goes through the second half of glycolysis. So this process happens twice. So each glyceraldehyde 3-phosphate gives us 2 ATP and that happens twice. So 2 times 2. We're really plus 4 ATP for the second half, so I'll just write end for the end for step 6 through 10. We also make one reduced coenzyme of NADH for every glyceraldehyde 3-phosphate that passes through the second half of glycolysis.
And we know that two glyceraldehyde 3-phosphates pass through that second half for every one glucose that starts it. So we end up with not just one, but two NADHH+. And remember, later on in the electron transport chain in oxidative phosphorylation, that's why I like to do this little curly Q, that's my way of saying later on down road in the electron transport chain and oxidative phosphorylation that reduced coenzyme is going to be reoxidized and it's going to power oxidative phosphorylation.
It's going to provide the energy for oxidative phosphorylation, that is the phosphorylation of ADP into ATP. And you might recall from tutorial 27 that each reduced coenzyme of NADH that gets reoxidized can synthesize 3 ATP. So times 3, we get 2 times 3, so we get 6 ATP.
Okay, so overall net yield from the breakdown of 1 glucose into 2 molecules of pyruvate is 6 ATP plus 4 ATP makes 10 minus the 2 it took to start. So the total is, kind of running out of room here, plus 8 ATP from 1 molecule of glucose. turning into the two 3-carbon molecules of pyruvate in glycolysis.
Alright, let's go ahead and go on to pyruvate oxidation. Let's find out how this molecule is turned into acetyl coenzyme A. So that three carbon molecule pyruvate is not ready to enter the Krebs cycle. First it has to be converted into the two carbon acetyl portion of acetyl coenzyme A and that happens through the process known as pyruvate oxidation. Pyruvate reacts with acetyl coenzyme A You might recall from tutorial 27 that coenzyme A has a thiol functional group, and it's going to react to form a thiol ester linkage to the 2-carbon acetyl group here.
So let's draw our acetyl coenzyme A. And the other carbon of pyruvate is oxidized fully to carbon dioxide. Since this is an oxidation, we know that it's going to be coupled to the reduction of a coenzyme.
So I'm going to show that here. Coenzyme NAD+, getting reduced to NADH. I will go ahead and write our enzyme name as well.
The enzyme is pyruvate. dehydrogenase. And that's how pyruvate gets converted into acetyl coenzyme A, which can then enter into the Krebs cycle and continue the catabolic process. Now under some conditions oxygen is not enough to continue reoxidizing the coenzymes in the electron transport chain. Remember oxygen is the ultimate acceptor of the electrons and the hydrogen ions in the electron transport chain.
electron transport chain. So under anaerobic conditions, when oxygen is not plentiful, the electron transport chain slows down, meaning that the oxidized forms of the coenzyme are going to be in short supply. Under those anaerobic conditions, pyruvate can actually become a source of the oxidized coenzymes by being reduced itself to lack of oxygen. So let's go ahead and write that down here, under anaerobic conditions.
Pyruvate, and we'll draw out the structure here, so I'm just redrawing pyruvate. can be reduced to lactate. And because the substrate, the pyruvate in this case, is being reduced, the coenzyme will be oxidized. So providing a source...
of the oxidized coenzyme NAD plus by being reduced itself. And that will help keep the process of glycolysis going because glycolysis requires the oxidized coenzyme NAD plus even under anaerobic conditions. And later on... that lactate can be reoxidized back into pyruvate, which can be oxidized into acetyl coenzyme A and undergo the Krebs cycle and etc.
Alright, so let's put this all together and look at our net yield of ATP from complete catabolism of glucose. Okay, so we're going to finish up today on slide 5 by looking at the net ATP yield for complete catabolism of 1 mole of glucose. Okay, so we know that glucose from the digestion of the carbohydrates that we eat first enters into, in complete catabolism, enters into the 10-step process of glycolysis. Now remember, let's go to a different color here.
We'll use the green. I think that'll make it really stand out. That in glycolysis, we're going to be minus 2 ATP to start in the first half. because that glucose molecule gets phosphorylated twice in the first half to make up the two phosphorylated molecules of glyceraldehyde 3-phosphate. So minus 2 ATP is just start in the first half of glycolysis.
But we're going to earn 4 ATP back in the second half, step 6 through 10. So plus 4 ATP at the end. So the end will refer to the second half, step 6 through 10. And remember, it's really plus 2 per glyceraldehyde 3-phosphate molecule passing through step 6 through 10, but we have two of them. Okay, so I'm going to write here as a little note, plus 2. G3P. Okay, for each glyceraldehyde 3-phosphate, for each D glyceraldehyde 3-phosphate molecule, we're going to get 2 ATP, so a total of 4. And then remember that we get 2 reduced coenzymes of NADH H+, as well.
And this is also at the end. And it's because you get one for every D-glyceraldehyde 3-phosphate molecule passing through that second half of glycolysis. So I'm going to write here, just to remind ourselves, plus one per G3P. Remember, my G3P is just me being lazy and not wanting to write out that whole name, D-glyceraldehyde 3-phosphate.
Okay. So, just a reminder, do my little curly cue, that the two reduced coenzymes of NADH are going to be reoxidized in the electron transport chain, powering oxidative phosphorylation. That is the phosphorylation of ADP into ATP.
And for every NADH that gets reoxidized in the electron transport chain, we can make 3 ATP. So times by 3, 2 times 3, we get 6 ATP. Okay, so total... Total 6 ATP plus 4 ATP, that's 10, but minus the 2 to start, so we're total plus 8 ATP for the process of glycolysis.
Now the process of glycolysis just breaks the glucose down into 2 3-carbon units of pyruvate ultimately. That's not ready for the Krebs cycle yet. First. that pyruvate has to be oxidized into carbon dioxide and a two carbon acetyl group of acetyl coenzyme A. And remember that that process is called pyruvate oxidation.
That one's easy to remember. Pyruvate oxidation. Okay. Now, every time...
a pyruvate gets oxidized into acetyl coenzyme A, a coenzyme gets reduced. So remember from this process, we get plus one NADHH plus, one reduced coenzyme of NADH. However, for one glucose molecule, remember you get two pyruvates, which means that you get two acetyl coenzyme A's in pyruvate. pyruvate oxidation. So this process happens twice for every glucose.
So really, we get plus one for the first pyruvate that undergoes pyruvate oxidation, and we get plus one for the second pyruvate that undergoes pyruvate oxidation. So I'm going to times this by two because it happens, I'm going to write a little note here, happens for four. Both pyruvates Ok, so the total is plus 2 NADH H plus, which we know that later on in the electron transfer chain is going to give us times 3 ATP, so 6 ATP. Ok, so let's really keep track here. We had 8 from the 10 stem of glycolysis and now we're seeing six for the two pi rubates being oxidized into acetyl coenzyme A.
So I'm gonna write plus six there. Okay we're not done yet we're doing complete catabolism all the way to carbon dioxide and water so after the glucose is converted into the two molecules of acetyl coenzyme a those molecules in complete catabolism will enter the Krebs cycle where they are completely oxidized to carbon dioxide. For each turn in the Krebs cycle, we get one guanosine triphosphate, which is a very similar molecule to adenosine triphosphate.
And because there are oxidation steps, we know that those oxidations... steps are going to be coupled to the reduction of coenzymes. So for one turn in the Krebs cycle, we're going to get three reduced coenzymes of NADH, H+, and one reduced coenzyme of FADH. Don't forget what happens to those.
They get re-oxidized in the electron transport chain, ultimately passing their electrons and hydrogen ions to oxygen from the air that we breathe, which gets converted into water. That highly exergonic process is used to power oxidative phosphorylation. It provides the energy for oxidative phosphorylation.
which is the phosphorylation of ADP into ATP. So it's right here. As these get reoxidized into 3 NAD+, and 1 FAD, that happens in the electron transport chain. The energy from the electron transport chain is harnessed to power oxidative phosphorylation.
Okay? So it's right here. Ultimately, oxygen accepts the electrons and hydrogen ions, becoming water. The energy released from that process is harnessed for oxidative phosphorylation, the phosphorylation of ADP into ATP.
And so from the Krebs cycle, do right here, from one turn in the Krebs cycle, remember that we get the three reduced coenzymes of NADH, H+, we've already said it, we're really just repeating ourselves here, and the one reduced coenzyme of FADH2. and the one high-energy guanosine triphosphate molecule, GTP. And when those reduced coenzymes are reoxidized, remember that for every 1 NADH that's reoxidized in the electron transport chain, it can power the synthesis of 3 ATP. So we're going to times this by 3. It gives us 9 ATP. But FADH2 enters later in the electron transport chain, giving us a lower yield of ATP, so we're going to times that one by two.
Don't forget that, times two. So one times two, two ATP. And then remember that we're... just going to count that GTP as an ATP.
It's a very similar molecule. So we're going to count it as an ATP. So for one turn in the Krebs cycle, that gives us 9, 10, 11, 12 ATP.
but how many times do we do we go through the Krebs cycle for one glucose molecule? Twice. Because one glucose is broken down into, in one glucose, I should put a one up there, is broken down into two acetyl coenzyme A molecules.
So for every one glucose undergoing complete catabolism we're going to We get two turns in the Krebs cycle, not just one. So times this number by two, we get 24 ATP. Okay, and we accounted for the electron transport chain and oxidative phosphorylation as we went along.
Okay, so that's how I like to do it. I like to account for those as we go along rather than accounting for those at the end. So I've been keeping track of...
the electron transfer chain and oxidative phosphorylation as we went. Okay, that's why I always put that little curly Q. As I say, later on in the electron transfer chain and oxidative phosphorylation, this is what we're going to get.
All right, so let's circle that in pink. And once we add up these three numbers, we will have our net yield of ATP for catabolism of one mole of glucose. Okay, so let's write it over here. One molecule of glucose is going to give us the plus the six plus the eight ATP so that's going to be 38 molecules of ATP, okay?
But I asked one mole of glucose, not one molecule, so I'm talking about 6.022 times 10 to the 23rd molecules of glucose, a mole of glucose. So for one mole of glucose, That means we're going to get 38 moles of ATP. And there's our answer right there.
So watch your units there. If your instructor is asking you about molecules, make sure that it's molecules of ATP. If your instructor is asking you about moles, then your unit should be in moles of ATP.
Now, last thing I want to say, and that will conclude our tutorial 28, is that... some instructors and some textbooks do use the more actual yields of ATP from the electron transport chain and oxidative phosphorylation which are 2.5 and 1.5 these are the maximum yields 3 and 2 are the max yields the more actual yields are 2.5 and 1.5 so if your instructor and or your textbook uses the actual yields then they will come out with 32 here instead of 38. So don't let that throw you off. Just make sure that you are being consistent with what your instructor wants you to do. Do they want you to use the max yield, which is what I am using, or do they want you to use the actual yield, which would be replacing the 3 with a 2.5 and replacing the 2 with a 1.5. Okay, that will conclude our tutorial 28. I hope that you will consider tuning in to Problem Set 28. Thank you very much.