Oxidative phosphorylation and the electron transport chain

- When we looked at glycolysis and the conversion of Pyruvate to Acetyl-CoA and then the Krebs or the Citric acid Cycle, we were sometimes directly producing ATPs but we were also doing a lot of reduction of NAD to NADH, and we later said that NADH, that that can later be oxidized, too, and that energy from that oxidation, that energy that's released from the electrons can be used to actually create ATP, and NADH is the main character here, but there are other coenzymes that are involved, like coenzyme Q, and you see that right over here. And what I want to talk about in this video is the process by which we actually are able to produce ATP from the oxidation of these coenzymes, and that process is what we call Oxidative Phosphorylation. Oxidative, Oxidative Phosphorylation. Now the main player, when we're talking about cellular respiration and Oxidative Phosphorylation, is NADH. NADH, in the process of being oxidized to NAD, so it gets oxidized to N... it gets oxidized to NAD, which has a positive charge, I often call it NAD+, but let's think about what this says. If we just look at this reaction from the point of view of NADH being oxidized, remember, oxidation is losing electrons, so NAD+, and then you're gonna have plus a hydrogen proton plus, you're going to have two electrons, plus two electrons. So this is what's happening when NADH is being oxidized into NAD, so this is Oxidation right over here. Let me do this in another color. So this is Oxidation, and this process of Oxidation, if these electrons get the appropriate acceptor molecule, it can release a lot of energy, and the eventual acceptor of those electrons, and I can show the corresponding reduction reaction, is we have two electrons, two electrons plus two hydrogen protons, or really, just two protons, a hydrogen nucleus is just a proton, it doesn't have a neutron for the main isotope of hydrogen. So two protons plus half of an oxygen molecule yielding, you put all of these two, all of these three, all of these things together, I should say, and you are going to get a water molecule. So you can think of it as the oxygen being the final acceptor of the electrons, and oxygen likes to be doing oxid-- likes to oxidize things, that's where the whole word Oxidation comes from. So here, (mumbles) oxygen likes to be reduced. It likes to hog electrons, so this is oxygen is being reduced. Oxygen, Oxygen reduced. So if you just directly transferred these electrons from our NADH to the Oxygen, it would release a lot of energy but it would release so much energy that you wouldn't be able to capture most of it. You wouldn't be able to use it to actually do useful work, and so the process of Oxidative Phosphorylation is all about doing this at a series of steps and we do it by transferring these electrons from one electron acceptor to another electron acceptor, and every time we do that, we release some energy, and then that energy can be, in a more controlled way, be used to actually do work, and in this case, that work is pumping hydrogen protons across a membrane, and then that gradient that forms can actually be used to generate ATP, so let's talk through it a little bit more. So we're gonna go, these electrons, they're gonna be transferred, and I won't go into all of the details, this is to just give you a high-level overview of it. They're going to be transferred to different acceptors which then transfer it to another acceptor, so it might go to a Coenzyme, Coenzyme Q, and a Cytochrome, Cytochrome C, and it keeps going to different things, eventually getting to this state right over here, where those electrons can be accepted by the oxygen to actually form the water, and the process, every step of the way, energy is being released. Energy is being released, and this energy, as we will see in a second, is being used to pump hydrogen protons across a membrane, and we're gonna use that gradient to actually drive the production of ATP. So let's think about that a little bit more. So let's zoom in on, on a mitochondria. So this is mitochondria. Let's say that's our mitochondria, and let me draw the inner membrane and then, these folds in the inner membrane, the singular for them is crista. If we're talking about plurals, cristae. So we have these folds in the inner, in the inner membrane right over here. So just to be clear, what's going on, this is the outer membrane, outer membrane. That is the inner membrane, inner membrane. The space between the outer and the inner membrane, the space right over here, that is the intermembrane space. Intermembrane, membrane space. And then the space inside the inner membrane, let me make that sure you can read that space properly, this space over here, this is the Matrix. This is the Matrix, and that is the location of our Citric acid Cycle or our Krebs Cycle, and I can symbolize that with this little cycle, we have a cycle going on here. And so that's where the bulk of the NADH is being produced. Now we also talked about some other coenzymes. In some books or classes, you might hear about FAD being reduced to FADH2, which can then be oxidized as part of Oxidative Phosphorylation. Other times, well actually, that's going to be attached to an enzyme, and then that FADH2 is used to reduce Coenzyme Q to produce QH2, and then that participates in Oxidative Phosphorylation, so you could think about either one of these. I'll focus on QH2. Well, why should we focus on NADH because it's all a similar process? FADH2 or QH2 enters a little bit later down this process, so they don't produce as much energy but they still can be used to help produce ATP, but anyway, our Citric acid Cycle, which we have shown in previous videos, that occurring in the matrix, and now let me do a little zoom in here, let me do a zoom in. So if I were to zoom in, let's say, let me do this in a color that we can see, so if I were to zoom in right over there, let's show this fold in the inner membrane, and it's very, and let's make it clear that this is, like all of these membranes, these are all phospholipid bilayers, so, let me draw, let me do the same color that I did in the, the actual diagram. So, we have... all these, we have a bilayer of phospholipids and I'm clearly not drawing any of this stuff to scale, so, almost done. All right, just to make it clear. And you have these enzymes that go across the phospholipid bilayer, and these enzymes are, and these protein complexes are actually what facilitate Oxidative Phosphorylation and this chain of enzymes, this chain of proteins, is what we call the electron, or what we call the electron transport chain. So we draw that. So maybe this is one protein, and I'm just drawing them as kind of these abstract... You could refer to the electron transport chain as these proteins or you could view it as this process of these electrons going from one acceptor to another, eventually making its way all the way to the oxygen. So that might be one protein, this is another protein right over here. I'll just do a couple, and this is really about a high-level overview, and what's happening is as the, and this is just gonna be a very high-level simplification of it, as you have your, let's say initially, your NADH comes in, so your NADH comes in, and it donates the protons and the electrons and then it become NAD+, so it just became oxidized, those electrons will go to an acceptor which then gets transferred to another acceptor then get transferred to another acceptor, and it goes through this electron transport chain and as that energy is released, that energy is used to pump hydrogen protons from the Matrix so this side right over here, the left side right over here, this is the Matrix. This is where our Citric acid Cycle occurs, so we have protons being pumped out, so we have these protons being pumped out as we release energy, as we go from one electron acceptor to another electron acceptor, and so electrons are going from higher energy states and they're releasing energy as they go down this kind of a, towards more and more electronegative things and they feel more comfortable with the water than they feel, than they felt with the NADH, and by doing so, by these electrons going down that gradient, I guess you could say, or maybe a better way, from going from a, a higher energy state to a lower energy state, we are creating this proton gradient, so the concentration of protons on the right side of this membrane, just to be clear where this is. This space right over here, this is right over there, that's the intermembrane space where the hydrogen proton concentration is building up. Now, this is stored energy because this is a electrochemical gradient, all this positive charge, they want to get away from each other, they want to go to this less positive Matrix right over here and also, just you have a higher concentration of hydrogens and just natural diffusion. They would want to go down their concentration gradient into the Matrix. There's less of the protons here. There's less of the protons in the Matrix than there are in the intermembrane space, and so, that's the opportunity to now take that energy and produce ATP with them, and the way that this happens, the way this happens, let me extend my membrane a little bit, that's a different color, so let me extend my membrane a little bit, is using a protein called ATP synthase. ATP synthase is actually a protein complex, I should say. So ATP synthase, really an enzyme, and ATP synthase goes across... It's actually a fascinating, fascinating molecule. I'll show a better diagram of it in a second, but your ATP synthase goes across the membrane, it actually has a fairly mechanical structure where it has a bit of a housing and it has an axle in the housing, so it looks, maybe, something like this, and it actually has something, you can view this as a, as a thing that maybe holds it together, so it's going across the membrane, I'll show a better diagram of it in a second. So then, of course, the membrane continues on, the membrane continues on, and what happens is it allows these hydrogen protons to flow down their electrochemical gradient, so these hydrogen protons go down and they actually cause the axle to spin, and so maybe I'll draw it this way. They actually cause the axle to spin as they go down their electrochemical gradient, and as this axle spins, this axle is not the smooth, it's not like it's made out of metal or something, it's made out of amino acids, so it's got this, it's all bumpy and all the rest, so it looks something like this, and what happens is you have ADPs, you have ADPs that get lodged in here, so let's say that's an ADP, and then a phosphate group, and they have actually three different sites where this can happen, so that's an ADP and a phosphate group, and there's another site that I'm not drawing, but as this thing rotates, it essentially keeps changing the confirmation protein and jams the phosphate group into the ADP which takes energy and locks them into place to form the ATP. When they form the ATP, they no longer attach to the active site and they let go. So you have this, actually, this mechanical motor, you can view this almost like a turbine, a water turbine. The water goes through it and then that energy is used to generate electricity. Here, hydrogen protons go down their electrochemical gradient, that rotary motion is then used to jam phosphate groups onto ADPs to form ATPs, and so this is the actual ATP production going on. And to get a better appreciation for what's going on, this is going on in your body right now, this is going on in my body, otherwise I wouldn't be able to talk. This is how I'm generating my energy. This is a more accurate depiction of ATP synthase right over here, and based on this diagram, this is our... let me make sure I... So this right over here, I'm having trouble drawing on this, let me see if I can... So this part right over here, this area right over there, that's our intermembrane space. This right over here is our, this over here is our Matrix. This membrane, this is a phospholipid bilayer, so if I wanted, I could draw the bilayer of phospholipids right over here, and this is our inner membrane or we could say this is a fold in the inner membrane, this could be on our crista, and so the hydrogen protons, they build up in the intermembrane space because of the electron transport chain, and then they flow down their electrochemical gradient, turn this rotor, and then they cause the creation of the ATPs over here, so you have ADP plus a phosphate group and then you produce your ATP. So this is fascinating, this is going on in the cells of your body, this is going on as we speak. It's not some abstract thing that is somehow separate from your reality. This is what is making your reality possible. So hopefully, you get a nice appreciation for this. I mean, we spent a lot of time talking about cellular respiration, we spent a lot of time talking about, OK, we can produce some ATPs directly through glycolysis and through the Citric acid Cycle, but mostly, most of the energy is because of the reduction of these coenzymes and especially, NAD to NADH, and then in Oxidative Phosphorylation and the electron transport chain, we use the Oxidation of the NADH to pump hydrogen protons from the Matrix to the intermembrane space, and then let them go back through, through the ATP synthase which jams the phosphate into the ADP to produce the ATP, which is our biological currency of energy.