- Krebs (citric acid) cycle and oxidative phosphorylation questions
- Oxidative phosphorylation questions
- The citric acid cycle
- Krebs / citric acid cycle
- Regulation of pyruvate dehydrogenase
- Regulation of Krebs-TCA cycle
- Electron transport chain
- Oxidative Phosphorylation: The major energy provider of the cell
- Oxidative phosphorylation and chemiosmosis
- Regulation of oxidative phosphorylation
- Mitochondria, apoptosis, and oxidative stress
- Calculating ATP produced in cellular respiration
Overview of the Electron Transport Chain. Created by Sal Khan.
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- Is the final product of ATP produced in the matrix?(86 votes)
- Yes but it gets translocated by the protein ATP translocase back into the intermembrane space (outer compartment), eventually back into the cytosol (cytoplasm). ATP translocase exchanges ATP for ADP, so ATP synthase will have more ADP to turn into ATP for the cell to use, just in case you were wondering how the ATP gets back out to the cell.(131 votes)
- Why isn't the equation 2e- + 2H+ + 1/2O2 = H20? I understand the oxygen angle and the 2 electrons (one from the NAD and one from the hydrogen ion.) I just don't see how the equation balances without a second hydrogen ion. Thanks!(72 votes)
- He corrects this in the next video: Oxidative Phosphorylation and Chemiosmosis
It is indeed a typo and there is suppose to be a 2 before the H(67 votes)
- Why do the H+ want to go back into the matrix? I know it must due to entropy but aren't the inside (matrix) and the outside part two closed systems?(15 votes)
- Diffusion causes them to want to go back across the membrane. They "want" to go down the concentration gradient.(10 votes)
- at17:16, what is the purpose of the water, or what happens to it?(9 votes)
- As well as energy (ATP), your body needs a lot of water (the 1-3 litres we drink would not be enough). It's needed in the blood, in mucus and serous membranes, for digestion, for enzyme reactions etc. It's a great solvent, acidity regulator etc.
It stays in your body until it is excreted with waste products.(16 votes)
- Are the proteins that the H+ ions are being pumped through always there, in the mitochondria? Or do they appear just for the purpose of ETC?(6 votes)
- The H+ ion gradient is constantly maintained, otherwise no almost ATP is produced and all your cells would die. A lot of poisons work this way (cyanide, DNP).(18 votes)
- When protons are pumped from the matrix to the outer compartment, Sal explains they want to come back in (to steer away from the concentration gradient). What prevents them from escaping the gradient the other way and go back into the cytoplasm?(5 votes)
- What prevents hydrogen protons from escaping from the mitochondria and entering the cytoplasm is the lipid bi-layer membrane of the mitochondria. As you might now, these lipids are uncharged. They allow for easy passage of uncharged particles but not for charged ones. Normally charged particles enter into membranes through pores. ATP-synthase, is similar to such a pore. It allows the proton gradient to escape but only into the matrix(10 votes)
- Does this all happen in our body?(2 votes)
- At9:57Sal talks about ATP synthase. I was wondering what is the difference between ATP synthase and ATPase or is there no difference?(3 votes)
- ATP synthase is an enzyme that uses the proton gradient to create ATP from ADP and inorganic phosphate.
An enzyme that is an ATPase is an enzyme that hydrolyzes ATP to do its job.(9 votes)
- How do the H+ ions know to pass through the ATP synthase? can they not diffuse out through the membrane? is it something to do with the charges on the protein channel? thanks :)(5 votes)
- We also know that for each electron that NADH and FADH2 deliver to the protein complex that belong to the electron transport chain, and amount H+ will be pump out to the inner membrane space. So that is how protons get to the inner membrane space and gradient forms.(1 vote)
- What happens to the NAD when NADH is broken down and when in the ATP Synthase, where does the phosphorus come from to make ATP from ADP? (And are the ADP molecules from Kreb's cycle? If so only two are made per glucose so where does enough ADP come from for the 36ATP made by on glucose?) Thanks!(5 votes)
After being done with glycolysis and the Krebs Cycle, we're left with 10 NADHs and 2 FADH2s. And I told you that these are going to be used in the electron transport chain. And they're all sitting in the matrix of our mitochondria. And I said they're going to be used in the electron transport chain in order to actually generate ATP. So that's what I'm going to focus on in this video. The electron transport chain. And just so you know, a lot of this stuff is known. But some of the details are actually current areas of research. People have models and they're trying to substantiate the models. But things are happening at such a small scale here that people can just look at the evidence, some of which is indirect, and say, this is probably what's happening. Most of this is very well established, but some of the exact mechanisms-- for example, how exactly some of the proteins work-- aren't completely understood. So I think it's very important for you to understand that this is at the cutting edge, that you're already there. So the basic idea here is that the NADHs-- and that's where I'll focus. FADH2 is kind of the same idea. Although its electrons are just at slightly lower energy state. So they won't produce quite as many ATPs. Each NADH is going to be-- as you'll see-- indirectly responsible for the production of three ATPs. And each FADH2, in a very efficient cell, in both of these cases, will be indirectly responsible for the production of two ATPs. And the reason why this guy produces fewer ATPs is because the electrons that he has going into the electron transport chain are at a slightly lower energy level than the ones from NADH. So in general, I just said indirectly. How does this whole business work? Well in general, NADH, when it gets oxidized-- remember, oxidation is the losing of electrons or the losing of hydrogens that happen to have electrons. We can write its half reaction like this. Its oxidation reaction like this. You'll have some NAD plus, which you can then go and use back in the Krebs Cycle and in glycolysis. You have some NAD plus, you'll have a proton, a positive hydrogen ion is just a proton. And then you'll have two electrons. This is the oxidation of NADH. It's losing these two electrons. Oxidation is losing electrons. OIL RIG. Oxidation is losing electrons. Or you can imagine it's losing hydrogens, from which it can hog electrons. Either one of those is the case. Now this is really the first step of the electron transport chain. These electrons are transported out of the NADH. Now, the last step of the electron transport chain is you have two electrons-- and you could view it as the same two electrons if you like-- two electrons plus two hydrogen protons. And obviously if you just add these two together, you're just going to have two hydrogen atoms, which is just a proton and an electron. Plus one oxygen atom, so I could say one half of molecular oxygen. That's the same thing as saying one oxygen atom. And you're going to produce-- if I have one oxygen and two complete hydrogens, I'm left with water. And you could view this, we're adding electron or we're gaining electrons to oxygen. OIL RIG. Reduction is gaining electrons. So this is the reduction of oxygen to water. This is the oxidation of NADH to NAD plus. Now, these electrons that are popping out of-- these electrons right here-- that are popping out of this NADH. And when they're in NADH they're at a very high energy state. And what happens over the course of the electron transport chain is that these electrons get transported to a series of, I guess you could call them transition molecules. But these transition molecules, as the electrons go from one to the other, they go into slightly lower energy states. And I won't even go into the details of these molecules. One is coenzyme Q, and cytochrome C. And then they eventually end up right here and they are used to reduce your oxygen into water. Now every time an electron goes from a higher energy state to a lower energy state-- and that's what it's doing over the course of this electron transport chain-- it's releasing energy. So energy is released when you go from a higher state to a lower state. When these electrons were in NADH, they were at a higher state than they are when they bond to coenzyme Q. So they release energy. Then they go to cytochrome C and release energy. Now that energy is used to pump protons across the cristae across the inner membrane of the mitochondria. And I know this is all very complicated sounding. And this is the cutting edge. So it maybe should sound a little complicated. Let me draw a mitochondria. So let me draw a small mitochondria just so you know where we're operating. That's its outer membrane. And then its inner membrane, or its cristae, would look like that. And let me zoom in on the membrane. So let's say if I were to zoom in right there. So if I were to zoom that out, that box would look like this. You have your crista here. And I'm going to draw it thick. So I'm zooming in. This green line right here, I'm going to draw it really thick. I'm going to color it in with the green, just like that. And then you have your outer membrane. This outer membrane, I can do it up here. And I'll just color it in. You don't even have to see the outside of the outer membrane. Right here, this space right here, this is the outer compartment. And then we learned in the last video, this space right here is the matrix. This is where our Krebs cycle occurred. And where a lot of our NADH, or really all of our NADH, is sitting. So what happens is, every time NADH gets oxidized to NAD plus, and the electrons keep transferring from one molecule to another, it's occurring in these big protein complexes. And I'm not going to go into the details on this. So each of these protein complexes span-- so let's say that's a protein complex where this first oxidation reaction is occurring and releasing energy. And then let's say there's another protein complex here, where the second oxidation reaction is occurring and releasing energy. And these proteins are able to use that energy to essentially pump-- this might all seem very complicated-- to essentially pump hydrogens into the outer membrane. It actually pumps hydrogen protons. And let me be very clear. Hydrogen protons into the outer membrane. And every one of these reactions pump out a certain number of hydrogen protons. So by the end of the electron transport chain, or if we just followed one set of electrons, by the time that they've gone from their high energy state in NADH to their lower energy state in water, by the time they've done that, they've supplied the energy to these protein complexes that span our cristae to pump hydrogen from the matrix into the outer membrane. So really the only byproduct of the oxidation of NADH into, eventually, water, or the oxidation of NADH and the reduction of oxygen into water, isn't ATPs yet. It's just this gradient where we have a lot higher hydrogen proton concentration in the outer compartment than we do in the matrix. Or you could say that the outer compartment becomes a lot more acidic. Remember acidity is just hydrogen proton concentration, the concentration of hydrogen protons. So the byproduct of all of this energy is used to really just pump these protons into the outer membrane. So you have two things. The outer membrane becomes more acidic than the matrix inside. Maybe we could call that basic. And obviously these are all positively charged particles. So there's actually an electric gradient, an electric potential between the outer membrane and the inner membrane. This becomes slightly negative, that becomes slightly positive. These guys wouldn't naturally do this on their own. If this is already acidic and it's already positive, left to its own devices, these more protons wouldn't be entering. And the energy to do that is supplied by electrons going from high energy state in NADH to going to a lower energy state, eventually, on the oxygen in the water. That's what's happening. But essentially all that's happening is protons being pumped from the matrix into the outer compartment. Now once that gradient forms, these guys want to get back in. These guys want to get back into the matrix. And that is where the ATPs are formed. So there's a protein that also spans this. Let me draw. Remember this is all this inner membrane right here. Let me just draw it a little bit bigger right here. So that's our inner membrane, our cristae right there. There's a special protein called-- and I'll show you actually a better diagram of what looks like in a second-- called ATP synthase. And what happens is, remember because of the electron transport chain, we have all of these hydrogen ions up here, all of these protons really. All they are is a proton. That really want to get back into the matrix down here. But they can't. This crista is impermeable to them so they have to find a special way to get through. They were able to go the reverse direction through the special protein complexes. Now they're going to go back into the matrix through ATP synthase. So they're going to go back, but something interesting happens. And this is really an area of current research where people think they know how it works but they're not sure. Because you can't just take these proteins apart and watch them operate like you can a regular mechanical engine. These are ultra-small and they have to be in a living system. And they have to have the right conditions. And you can't even-- it's hard to see hydrogen protons. These are ultra-small things that are, pretty much, you can't see them. But what happens, the current model is, as these enter, as these go through my ATP synthase there's actually an axle. So you can kind of view this as a housing. And then there's an axle. And this is all just a big protein. And there's an axle and then there's another part of the synthase down here. So you can imagine, this is kind of mind-blowing. That something this fancy is occurring on the membranes of pretty much all living systems' cells. It's not just eukaryotes. Even prokaryotes do this. They don't do it in their mitochondria; they do it in their cellular membrane. But it's a pretty neat thing. And what happens is, as these go through, you can kind of imagine as water flowing through a turbine. It mechanically causes this structure in the middle to spin. To actually spin. This is the current thinking. And this thing is all uneven. It's not, like, this nice tube. It'll look all crazy like that. And what happens is that an ADP molecule-- let's say that this is the A part of the ADP. And then you have two phosphate groups. It'll attach to one part of this protein. And maybe a phosphate will just randomly attach to another part of this protein. Just like that. So right now it's just ADP and a phosphate. But as this inner axle turns-- because it's not a symmetrical tube, it has different things sticking out that have different amounts of atomic charge and it's going to play with this outer housing right here. And so as this turns, the outer housing, because of just the proteins bumping against each other and electrical charge and whatever else, it's going to squeeze the ADP and the phosphate together to form, actually form, ATP. And actually the current thinking is that it does it on three different sites simultaneously. So as this spins around, ADP and phosphate groups kind of show up on the inside of this housing. You could imagine it like that. And I don't even know if it's on the inside. But they show up on the housing. And as this thing spins around, it stretches and pulls on this outer part and pushes these two things together. So it's using the energy from this proton gradient to drive this axle. And because it's all strange, it does all these distortions on this outer part and actually pushes the two ATPs together. So when you start off with your 10 NADHs, it'll provided just enough energy and just enough protons to put into the outer membrane that when they go back through our ATP synthase-- you could almost view it as an ATP synthase motor-- just based on people's observations they see that this will produce, on a per-NADH level, roughly three ATPs. On a per-FADH2 level, roughly two ATPs. And I've said multiple times in the videos, this is kind of an ideal. That a lot of times, maybe you'll have some protons leak, so their energy can't be captured properly. Or maybe some of these electrons might somehow jump the gun or jump some steps, so some of the energy gets lost. So you don't always have a completely efficient system. And just so you believe that this is actually occurring on our membrane, there's actual visual depictions of these proteins. This is the actual protein structure of ATP synthase right here. That is actually ATP synthase. And as you can see, there's this piece right here that holds this part and that part. You can kind of imagine it relatively stationary. The hydrogen comes through here. The axle gets spun. And as the axle gets spun, ADP and phosphate groups that are lodged inside this F1 part of the protein, get pushed together. You have to put energy into the reaction in order to make them stick together. But they get pushed together by the protein itself as this axle turns around. And this axle turns around from the energy of the hydrogen going. I don't even know what the mechanics would look like. But you could imagine-- in my head I imagine, the simplest thing is a windmill. Or not a windmill, as maybe some type of water turbine or maybe the simplest thing is, if you have something like that. I don't know if that's what the protein actually looks like. If you have any kind of thing passing by, it's going to spin it. It's going to spin it like that. And you could be more creative if you want to change the angle of the spin and whatnot. And that's all, people are really still trying to understand this at a deeper and deeper level. But for your purposes, especially in an introductory biology level, you just have to realize that two things are happening in the electron transport chain. Electrons are moving from the NADHs and the FADH2s to eventually show up and reduce the oxygen. And as they do that, they're releasing energy as they go from one molecule to another. They're going to lower energy states. That energy is used to pump hydrogen protons into the outer compartment of the mitochondria. And then that gradient, those hydrogen protons want to get back into the matrix of the mitochondria. So as they go back in, that drives this ATP synthase engine, which actually produces the ATP. So just like we said in the past, when you have 10 of these, on average-- let me say this way-- on average each NADH is going to produce 3 ATPs. Not directly. It produces enough of a gradient of hydrogen protons to produce 3 ATPs in the ATP synthase. And each FADH2, on average, produces enough of a hydrogen gradient to produce 2 ATPs. So if we come in with 10 NADH, they're going to produce-- in this ideal world-- 30 ATP. And then our 2 FADH2s are going to produce 4 ATP. And then if you remember from glycolysis, we had 2 net ATPs directly produced. And from the Krebs cycle we had 2 ATPs directly produced. So then you have 4 from glycolysis and Krebs, and that gets us, once again, to our magic 38 ATPs from one molecule of glucose. And now, I think you have a pretty good grasp of cellular respiration.