Thursday, May 18, 2017

Overview of cellular respiration

[Voiceover] So what I wanna do in this video is give ourselves an overview of cellular respiration. It can be a pretty involved process, and even the way I'm gonna do it, as messy as it looks, is going to be cleaner than actually what goes on inside of your cells, and other organs themselves, because I'm going to show clearly from going from glucose, and then see how we can produce ATP through glycolysis, and the Krebs cycle, and oxidative phosphorylation, but in reality, all sorts of molecules can jump in at different parts of the chain, and then jump out at different parts of the chain, to go along other pathways. But I'll show, kind of the traditional narrative. So we're gonna start off, for this narrative, we're gonna start off with glucose. We have a six-carbon-chain right over here. And we have the process of glycosis, which is occurring in the cytosol, the cytosol of our cells. So if this is a cell right over here, you can imagine, well the glycolysis, the glycolysis could be occurring right over there. And that process of glycolysis is essentially splitting up this six-carbon glucose molecule into two three-carbon molecules, and these three-carbon molecules, we go into detail in another video, we call these pyruvate. Pyruvate. And in the process of doing so, and this is, I guess you could say, the point of glycolysis, we're able to, on a net basis, produce two ATP's. We actually produce four, but we have to use two, so on a net basis, we produce two ATP's. I'm gonna keep a little table here, to keep track. So we produce two ATP's, and we are also, we're also, in the process of that, we reduce two NAD molecules to NADH. Remember, reduction is gaining of electrons. And you see over here, this is positively charged, this is neutrally charged, it essentially gains a hydride. So this is reduction. Reduction. And if we go all the way through the pathway, all the way to oxidative phosphorylation, the electronic transport chain, these NADH's, the reduced form of NAD, they can be, then, oxidized, and in doing so, more energy is provided to produce even more ATP's, but we'll get to that. So you're also gonna get two NADH's. Two NADH's get produced. Now at that point, you could kind of think of it as a little bit of a decision point. If there's no oxygen around, or if you're the type of organism that doesn't want to continue, for some reason, with cellular respiration, or doesn't know how, this pyruvate can be used for fermentation. We have videos on fermentation, lactic acid fermentation, alcohol fermentation, and fermentation is all about using the pyruvates to oxidize your NADH back into NAD, so it could be re-used again, for glycolysis. So even though the NADH has energy that could eventually be converted into ATP, and even though pyruvates have energy that could eventually be converted into ATP, when you do fermentation, you kinda give up on that, and you just view them as waste products, and you use the pyruvate to convert the NADH back into NAD, And then, glycolysis can occur again. But let's assume we're not gonna go down the fermentation pathway, and we're gonna continue with traditional aerobic cellular respiration, using oxygen. Well, the next thing that's going to happen, is that the carboxyl group, and and everything I'm going to show now, it's going to happen for each of these pyruvates. So, you can imagine these things all happening twice. So I'm gonna multiply a bunch of things, times two. But what happens in the next step, is this carboxyl group, this carboxyl group is stripped off of the pyruvate, and it, essentially, is going to be released as carbon dioxide. So this is our carbon dioxide being released here, and then the rest of our pyruvate, which is, essentially, an acetyl group, that latches onto coenzyme A. And you'll hear a lot about coenzyme A. Sometimes I'll write just CoA, like this. Sometimes I'll do CoA, and then the sulfur, bonded to the hyrdrogen. And the reason why they'll draw the sulfur part, is because the sulfur is what bonds with the acetyl group, right over here. So, you have the carbon dioxide being released, and then the acetyl group, bonding with that sulfur, and by doing that, you form acetyl-CoA. And acetyl-CoA, just so you know, you only see three letters here, but this is actually a fairly involved molecule. This is actually a picture of acetyl-CoA, I know it's really small, but hopefully you'll appreciate that it's a more involved molecule. That, the acetyl group that we're talking about is just this part, right over here, and it's a coenzyme. It's really acting to transfer that acetyl group, and we'll see that in a second. But it's also fun to look at these molecules, because once again, we see these patterns over and over again in biology or biochemistry. Acetyl-CoA, you have an adenine right over here. It's hard to see, but you have a ribose, and you also have two phosphate groups. So this end of the acetyl-CoA is essentially, is essentially an ADP. But it's used as a coenzyme. Everything that I'm talking about, this is all going to be facilitated by enzymes, and the enzymes will have cofactors, coenzymes, if we're talking about organic cofactors, that are gonna help facilitate things along. And as we see, the acetyl group joins on to the coenzyme A, forming acetyl-CoA, but that's just a temporary attachment. The acetyl-CoA is, essentially, gonna transfer the acetyl group over to, and now we're going to enter into the citric acid cycle. It's gonna transfer these two carbons over to oxaloacetic acid, to form citric acid. So it's gonna transfer these two carbons to this one, two, three, four carbon molecule, to form a one, two, three, four, five, six carbon molecule. But before we go into the depths of the citric acid cycle, I wanna make sure that I don't lose track of my accounting, because, even that step right over here, where we decarboxylated the pyruvate, we went from pyruvate to acetyl-CoA, that also reduced some NAD to NADH. Now, this is gonna happen once for each pyruvate, but we're gonna- all the accounting we're gonna say, is for one glucose molecule. So for one glucose molecule, it's gonna happen for each of the pyruvates. So this is going to be times- This is going to be times two. So we're gonna produce two, two NADH's in this step, going from pyruvate to acetyl-CoA. Now, the bulk of, I guess you could say, the catabolism, of the carbons, or the things that are eventually going to produce our ATP's, are going to happen in what we call the citric acid, or the Kreb cycle. It's called the citric acid cycle because, when we transferred the acetyl group from the coenzyme A to the oxaloacetic acid, we formed citric acid. And citric acid, this is the thing that you have in lemons, or orange juice. It is this molecule right over here. And the citric acid cycle, it's also called the Kreb cycle, when you first learn it, seems very, very complex, and some could argue that it is quite complex. But I'm just gonna give you an overview of what's going on. The citric acid, once again, six-carboned, it keeps getting broken down, through multiple steps, and I'm really not showing all of the detail here, all the way back to oxaloacetic acid, where, then, it can accept the two carbons again. And just to be clear, once the two carbons are released by the coenzyme A, then that coenzyme A can be used again, to decarboxylate some pyruvates. So there's a bunch of cycles going on. But the important take-away, is as we go through the citric acid cycle, as we go from one intermediary to the next, we keep reducing NAD to NADH, in fact, we do this three times for each cycle of the citric acid cycle, but remember, we're gonna do this for each acetyl-CoA. For each pyruvate. So all of this stuff is going to happen twice. So we're going to go through it twice for each original glucose molecule. So, here we have one, two, three NADH's being produced, but since we're going to go through it twice, and we're gonna be accounting for the original glucose molecule, we could say that we have six six NADH's, or you could say, six NAD's get reduced to NADH. Now, you also, in the process, as you're breaking down, going from the six-carbon molecule to four-carbon molecule, you're releasing carbon, as carbon dioxide, and you also have, traditionally GDP being converted into GTP, or sometimes ADP converted into ATP, but functionally, it's equivalent to ATP, either way. So, we could also say that we're gonna directly- Remember, we're gonna do all of this stuff twice. So, we could say that two, I'll just say two ATP's, to make it simple. We could say GTP, but I'll say two ATP's. Because once again, this happens once in each cycle, but we're gonna do two cycles, for each glucose. And then, we have this other coenzyme right over here, FAD, that gets reduced to FADH2, but that stays covalently attached to the enzymes that are facilitating it, so eventually, that's being used to reduce . coenzyme Q to QH2. So I'm just gonna write the QH2 here, but once again, you're gonna get two of these. So two QH2's. Now let's think about what the net product, over here, is going to be. And to think about it, we should just, we'll just- I'll do a little bit of a shorthand. We'll go into more detail in future videos. These coenzymes, the NADH, the QH2, these are going to be oxidized, during oxidative phosphorylation, and the electron transport chain, to create a proton gradient across the inner membrane of mitochondria. We're gonna go into much more detail in the future, but that proton gradient is going to be used to produce more ATP. And one way to think about it, is each NADH is going to produce, and I've seen accounts, it depends on the efficiency, and where the NADH is actually going to be produced, but it's going to produce anywhere between two and three ATP's. Each of the reduced coenzyme Q's, so QH2, that's going to each produce about one and a half ATP's. And people are still getting a good handle on exactly how this is happening. It depends on the efficiency of the cell, and what the cell is actually trying to do. So, using these ranges, actually I'll say one and a half to two ATP's. And these are approximate numbers. So let's think about what our total accounting is. So if we just count up the ATP or the GTP's, we're gonna get two there, two there. So we're gonna have four direct, or very close to direct, ATP's net, being created. And then how many NADH's? We have two, four, and then we add six. We have ten NADH's. Ten NADH's. And then, we have two of the coenzyme Q's. Two QH2's. So that's gonna be four ATP's, this is going to be between- this is going to be between 20 and 30 NADH's. Sorry, 20 and 30 ATP's. 20 to 30 ATP's. And then, this is going to be three to four. Three to four ATP's. So if you add them all together, if you add the low ends of the range, you get, let's see, 20 plus three, plus four. That's 27 ATP's. 27 ATP's. And the high end of the range, let's see. You have four plus 30 plus four. You have 38. 38 ATP's. And 38 ATP's is currently considered to become the theoretical maximum, but when we actually observe things in cells, it looks like it comes right at around 29 to 30 ATP's. And once again, it depends what the cell's trying to do, the type of cells, and the type of efficiency. But all of this is happening through cellular respiration. And just to get a better sense of where all of this is occurring. Where all of this is occuring, we said glycolosis is occurring in the cytosol. The citric acid cycle, this is occurring in the matrix of the mytochondria. So this space right over here, that is the citric acid cycle, in that little magenta space that I've drawn. So that's the matrix. In the video on mitochondria, we go into much more detail on that. And then, the actual conversion of the coenzymes, of the electron transport chain, that's occurring across the membrane of the crista. And the crista are these folds, these kind of, inner membrane folds, of our mitochondria. So, it's occurring across the membranes of those, actually the plural is cristi. Crista is the singular of the cristi. And we'll go into more detail into that, in other videos.

Questions & Replies.

Q:What is the QH2 that Sal was talking about? In my classes, we only learned about FADH2, not about QH2. Is it important that we know this?

R:Q is the coenzyme Q, an antioxidant called ubiquinone with vitamin-like properties, and QH2 is the reduced form of the coenzyme. I have to acknowledge that Sal is right in using QH2 as the electron carrier. Although textbooks teach that FADH2 does this, it is not correct. FADH2 remains bound to the Succinate dehydrogenase (complex II) and as such it does not carry the electrons to the next complex III (cytochrome bc1); QH2 does. Therefore, QH2 is the "true" electron carrier. Regarding what you have to learn? Keep in mind that you need to pass the exam, thus, it would be better to use FADH2 as your answer, but remember that it is wrong until the AP college board changes its thinking. There is an excellent discussion on using QH2 instead of FADH2:

Q: What is GTP and GDP??

R: Excellent question!
GTP stands for Guanine Triphosphate, and GDP for guanine diphosphate. These function in a very similar way to ATP and ADP, and most of the GTP produced in the krebs cycle is used to turn ADP into ATP. GTP and GDP also play a role in other cellular functions, though, such as g-protein coupled receptors.
ATP (and GTP) are like a fully charged battery. Lots of energy for a cell to use. ADP (and GDP) are like partially charged batteries. They still contain some energy in the remaining phosphate bond, but not as much energy as in ATP, which has a second high energy bond.

Q: How can you have 1.5 atp's?

R1: Maybe because the number of H ions that specific electron carrier(QH2) can pump via the electron transport chain into the reserve are more than required to make one complete ATP and less than the number of protons required to make 2 ATP.

R2: I believe its an approximation because they probably calculated that an average between 1-2 ATP gets produced.
R2.1: That still isn't clear. You can't have half a molecule. They need to be whole numbers.

Q: So a muscle cell in an environment with a large amount of oxygen available would produce a number of ATP closer to the maximum 38 ATP versus a skin cell in an environment with less oxygen available?

R: Yes. More oxygen (and the mere presence of it) defiantly increase ATP production, although there is a threshold above which more oxygen will not increase ATP production.

Q: Do every cell in our body produce the exact same amount of ATP by completely oxidizing glucose?

R: I'm not sure, but I think the answer is yes. The mitochondria in your cells are more or less the same, and all of your cells undergo the same process of cellular respiration (that is, the ones that undergo it. Some cells, such as red blood cells or cells that are part of the urethra do not have mitochondria and don't perform cellular respiration.

Q:  NAD+ --> NADH. Where does the proton come from? Is it just floating around in the cytosol?

R1: Hmm... well, this might be a bit late, but to explain in the best way I can, there's a lot of H+ (hydrogen ions) that are drifting around. They're the reason why the electron transport chain is needed in the first place, in order to bring in more hydrogen ions against the concentration gradient. The hydrogen ions are very high-energy, so they react with NAD+ to make it become NADH.
I'm very sorry if that didn't help, I'm rather new to this topic myself. I just hope it helped a little. 

R2: No, that makes sense. Thanks!

Q: What is the difference between NADH and NADPH?

R: The difference between NADH and NADPH is that NADPH has an extra phosphate group. While NADH is used to power cellular reactions such as glycolysis, during which molecules are broken down, NADPH is used to power photosynthesis.

Q: If cellular respiration produces 10 x NADH molecules then where do the NAD+ come from to reduce into NADH?

R1: Every time NADH drops off the electrons in the ETC, it becomes NAD+ again and can be recycled.

R2: There is always a big pool of both NAD+ and NADH around as the reaction can go in both directions.
Also NAD+ can be made by the cell directly, either from scratch starting with the amino acid tryptophan or breaking up other molecules like Niacin/vitamin B3 (which has to be taken up via food first).

Q: What is an acetyl?

R: In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3.

Q: If oxygen is present what is the sequence of processes that occur in cell respiration?

R: If oxygen is present, the sequence of processes that occur in cellular respiration are:
1. Glycolysis -> 2. Pyruvate Oxidation -> 3. Citric acid cycle (a.k.a Kreb's cycle) -> 4. Oxidative phosphorylation (a.k.a Electron transport chain). These processes combined produce 38~ net ATPs.
However, if oxygen is not present, only Glycolysis can occur.

Q: Where does oxygen come into play during the Kreb's cycle? All I know is that it's required (because otherwise, fermentation) but I don't see it anywhere here.

R: Oxygen is needed for the electron transport chain.

Q: What does "pi" mean(ATP turns to ADP+pi+energy)?

R: It's an Inorganic phosphate.

Q: How does FAD reduce into FADH2? It should be just FADH right?

R: Well, yes Q is the coenzyme Q, an antioxidant called ubiquinone with vitamin-like properties, and QH2 is the reduced form of the coenzyme. I have to acknowledge that Sal is right in using QH2 as the electron carrier. Although textbooks teach that FADH2 does this, it is not correct. FADH2 remains bound to the Succinate dehydrogenase (complex II) and as such it does not carry the electrons to the next complex III (cytochrome bc1); QH2 does. Therefore, QH2 is the "true" electron carrier.

Q: How does GDP/ADP become GTP/ATP?
R: With an inorganic free phosphate group.

Q: Is cytoplasm and cytosol same?
R: No. cytoplasm is jelly like matter in cell where all organelles reside but cytosol is the soluble part of cytoplasm.

Q: Where did the O2 go?
R1: The O2 is not released in the Krebs cycle nor it is a waste product of cellular respiration. CO2 is.
R2: The O2 is usually just a waste product of Cellular Respiration. It will most probably be used else where in the body.

Q: Why does the cell not want to make as many ATP's as possible? I have heard that sometimes the cell does not fully maximize Cellular Respiration. Even though the cell has the capability to make 38 ATP, it chooses not to and instead makes less. Why is this?

R1: Not all the energy released in the exergonic reactions of cellular respiration goes into making ATP - there are other kinds of work the cell can perform using it.

R2: Not sure about making less per cycle, but they don't over make it so there is no waste for the amount of work that was put in to make it!

Q: So in glycolysis, the number of hydrogen atoms are less than what was to begin with. I can understand that two hydrogen protons are used to reduce the NADH, but we start out with 12 hydrogen and only end up with 6. What happens to the other six?

R: Glycolysis is actually ridiculously complex: 

If you follow that through you should find out where the missing hydrogens are going, but I'm not sure you want to.

Q: What is the purpose (goal) of cellular respiration?

R: To convert glucose, a sugar, into ATP, energy that cells can use (they can't use glucose directly!).

Q: Does NAD gain two hydrogen or one?

R1: Once NAD is reduced to NADH it receives one hydrogen proton.

R2: NAD is reduced and become positive electrode. Then according to biologic point of view, it tends to relieve or gain one hydrogen atom being NADH. Hope that helps.

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