- Abbreviations: Electron Transport Chain= ETC and Oxidative Phosphorylation= OxPhos
- Terms to understand: combustion reaction, redox, inner membrane space, matrix, proton gradient
- The ETC & OxPhos occur in the inner mitochondrial membrane
- The ETC is part of the redox reaction: hydrocarbon + O2 –> CO2 + H2O
- As the ETC occurs, protons are pumped into the inner membrane space, creating a proton gradient
- OxPhos uses this proton gradient to drive ATP synthesis ADP + P –> ATP
- The “long, slow” combustion reaction
- Hydrocarbon + O2 –> CO2 + H2O where the hydrocarbon comes from the food we eat, the O2 comes from the air we breathe; we turn these into carbon dioxide (which we exhale) and water.
- Compared to a car, which carries out combustion with a BANG!, our bodies do it more slowly & carefully.
- The thermodynamics (i.e. the amount of energy released) is essentially the same between these two scenarios (car vs body), but our bodies pass the electrons through many (many!) redox centers, so that there is no BANG!
- Kreb’s Cycle (& mitochondria) review
- Recall the inner folds of mitochondria: they separate the “inner membrane space” from the “matrix”.
- The ETC and OxPhos are located in the inner mitochondria membrane.
- The Kreb’s Cycle generates CO2, GTP, NADH & FADH2
- The two “special” carbons of acetylCoA each become a carbon in the CO2 (which we then exhale)
- The GTP turns into an ATP by transferring a phosphate to an ADP
- NADH and FADH2 deliver electrons to the ETC (see below)
- Electron transfer
- The ETC is comprised of four multi-protein complexes (named I, II, III & IV)
- Multiple redox centers are held in place by these proteins;
- These redox centers become reduced when they accept electrons and then become oxidized when they donate electrons to the next redox center in the chain
- How the process happens:
- Electrons from NADH are accepted by Complex I
- Electrons from FADH2 are accepted by Complex II
- Note: it is the –H (a proton with 2 electrons) on the NADH and FADH2 that leave each of these molecules, turning them back to NAD+ and FAD.
- Eventually the electrons are transferred (along with 2 protons) to the oxygen atoms of O2, thus creating H2O; this happens in Complex IV.
- Throughout this whole redox reaction, protons are pumped into the inner membrane space.
- ATP Synthase (aka Complex V)
- OxPhos is the result of the electron transfer coupled to ATP synthesis
- Note that there are many more H+ in the membrane space compared to matrix. This is referred to as a “proton gradient”. There is a driving pressure for these H+ to equalize and they “want” to pass through the ATP synthase
- Important structural aspects of ATP Synthase
- The “merry-go-round” part moves when protons bind to it. The protons make their way through the synthase eventually reaching the matrix.
- As the “merry-go-round” goes round, it drives a “rotor” that creates different shapes in the synthase part of the complex.
- One of the regions binds ADP & P
- Another region closes down on an ADP & P putting them in perfect proximity to create a bond between them
- The third region then releases a newly formed ATP.
- The ETC & OxPhos are the finale of the “long slow” redox reaction that gives us energy
- Electrons from the hydrocarbons we eat are passed through multiple redox centers until they eventually make it to oxygen (along with protons), thus creating water.
- As the electrons pass through Complexes I to IV, protons are pumped into the inner membrane space.
- As the protons return to the matrix, by passing through ATP synthase, ADP and P are given a place to create a bond, thus making ATP
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Hey there. What we’re going to talk about today are the electron transport chain and oxidative phosphorylation. I like to give these two some abbreviations. So, we’ll call this the ‘ETC’, and then oxidative phosphorylation we’ll abbreviate just as ‘oxphos’. This has got to be one of the coolest areas of biochemistry. I’m gonna probably say that for all the areas, but I just I love this one. I think it’s super neat.
The basic idea is: We’ve been talking about this hydrocarbon reaction combustion reaction…we take hydrocarbons plus O2, two making CO2 plus water, right? This is the hydrocarbon, we eat oxygen when we breathe, we exhale CO2, and some water gets made along the way. We’re going to go into the details of how this actually happens to create energy. I call it a ‘long, slow combustion reaction’ because it takes place in tiny little bits. We’ll talk about that on the next slide.
This is a redox reaction…electrons are being transferred. A redox reaction in biochemistry…it’s sometimes a little hard to tell…but one of the quick ways is to remember that molecular oxygen is an element in its natural state like that, it has an oxidation state of 0. If we come over here, remember oxygen has an oxidation state of -2. (If it’s in a molecule, particularly like water, because each of those two H+s is a +1.) So that balances out to being 0 for the whole molecule. You can do the same thing for the carbon over here, but the carbons in hydrocarbons often have a variety of different oxidation states. I can tell you that they’re -2 or -4 or zero, that sort of thing. But over here in CO2, you’ve got 2 oxygen’s with a negative two oxidation state, so that means you’ve got a total of -4 there. That means this carbon at the CO2 as a +4. Remember LEO and GER, if we go from something – up to +, then that’s going to be loss of electrons (LEO) because remember electrons are negative. So we’re losing the negativity to become positive. And so that’s going to be the oxidation. A little clearer is the gain of electrons (GER). If you go from 0 to -2, that’s going to be a gain of electrons. So that part there is the reduction. So yeah, electrons are getting transferred because it’s a redox reaction.
Interestingly, as the electrons are transferred, protons are going to get pumped…remember a proton is just that little H+. So we’ll look for that. As that happens, that is going to be the driving force that allows ATP to get synthesized from ADP + P. The combustion reaction that takes place in us is not all that different than the one that takes place in your car. We’ve got molecules that are high energy, these hydrocarbons and oxygen, and they’re going to turn into more stable molecules, namely CO2 and water. We’re going to go have a reaction that looks something like that. And this amount here is going to be the energy that gets produced. In your car, this happens in a great big boom, right? So that’s going to take place in the piston (actually cylinder) and that’s what drives the piston to move. That’s going to drive your car forward. And so it’s explosive.
That’s what also happens in us. It could be pretty much the same energy difference going from the foods we eat to making the CO2 and water. But what’ll happen here is we’re going to go through lots of little redox centers. We go up and down and up and down and up and down and up and down and up and down and up and down. And I’m not even coming close to showing how many different little redox centers…I’ll show you examples of what those look like. But redox centers are molecules that accept electrons and then release the electron. So here it’s accepting it, releasing it, accepting it, releasing it, and as it goes down. The same amount of energy is going to come from it, but because it happens long and slow, we don’t have some great big explosion taking place when we eat food.
Let’s do a little review of the Kreb’s cycle because that’s really how the entry into the electron transport chain is…from the Kreb’s cycle. This takes place in the mitochondria. Let’s draw ourselves a little mitochondrion over here. It has these folds in it…let’s just draw this inner membrane. One of the things to note is that this inner membrane sealed up back on itself. And so this is called the matrix on the inside and this is called the inner membrane space on the outside here. It’s still inside of the mitochondria though. What we’re going to be talking about…I’m going to draw a membrane little bit and that membrane is this one here, that’s curling around on the inside of the mitochondria. The Kreb’s cycle takes place in the mitochondria.
So for the electron transport chain and oxidative phosphorylation…the basic idea of the Kreb’s cycle is that those two carbons from acetylCoA–the two carbon chunk–that’s going to enter into the Kreb’s cycle and it’s going to turn into two CO2. (That’s an example of making the CO2 from that combustion reaction.) As that process happens, we’re going to generate high energy molecules: NADH, FADH2 and GTP. GTP can turn into ATP pretty easily just by transferring its third phosphate over to the ADP and to make an ATP. So that one, we don’t worry about too much. But the electron transport chain is really about the NADH and FADH2 delivering their energy and electrons to the transport chain.
Here is the electron transport chain. These are Complexes I, II, III, IV, and V. (I’m trying to create a little membrane here and I’m leaving some space over here for the V Complex.) V is going to sit over here. So we’ve got four complexes that are part of the electron transport chain. And then we’ll put this other guy over here. Some things to note, this is where NADH…and I’m going to make it like that…these electrons that are right in here in this bond, that’s what’s going to get delivered to Complex I and FADH2 is going to deliver its electrons here Complex II. This is where those little redox centers are…and I’ll show those on the next slide. Redox centers are embedded within the proteins, and so the electrons from these molecules are just going to get passed from redox center to redox center. And they’re going to have this little path through it. It’s almost like a wire system. The electrons can pass through the backbone of the protein through these different redox centers. And so it’s just a way of having those electrons move in a very controlled manner, eventually making it through redox centers that are here in Complex IV. This is the coolest spot because this is where the oxygen molecule is going to get split into 2 O’s, then each of those O’s is going to gain an electron and a proton. (This will be a new electron, this is a new electron and then here’s a hydrogen proton.) This hydrogen and this hydrogen are going to get added to this oxygen and voila, that’s how you have your H2O. So that’s happening here in Complex IV, which is really kind of a neat part of it.
So redox centers…here’s what they look like. This guy here is known as FMN. The idea is that, let’s say that the H from the NADH comes in and attaches to it. It grabs on over here and then these electrons are going to move through and then maybe come out and grab onto a proton, something like that. That’s how this (FMN) is gaining electrons. But those electrons could go in the reverse…those electrons can leave and maybe come over here would be next to this iron sulfur cluster. And that’s where you could have an Fe3+ turn into an Fe2+, because it gained an electron. (Remember: the electron is negative). So it made the iron more negative…went from the 3+ to a 2+, and the same thing can happen over here. This could be a 3+, then that could turn into a 2+. This is a heme–there’s lots of these sort-of-like structures that are in the electron transport chain. There’s so many, it’s really cool. And then at that last step with the oxygen, it’s copper, that’s involved. And so you have Cu2+ going to Cu1+. These guys will just keep going back and forth, so when it accepts the electron, it turns into plus one (it’s going to gain the electron to get to 1+), but then it’ll lose that electron and go back to 2+. It keeps going back and forth between those two to allow the electrons to eventually make their way to that oxygen, where it turns into water.
Here we have our Complex V. So again, we’ll make our membrane here. Those electrons as we talked about are getting passed through, through, through all these little areas coming over here, as that happened, protons were getting pumped out here into the inner membrane space. So we end up with lots of little protons (H+) sitting out here in the intermembrane space, and they’re not down here in the matrix. This creates a gradient. You’ve got lots here, not a lot here. There’s just sort of a natural tendency for things to equalize–to equal out. So these protons have a driving force to come through this Complex V. Note, Complex V is called the ATP Synthase because as these protons pass through the ATP synthase, then they’re going to create ATP out the other end.
How does that happen? Well, these H+s are going to end up being able to bind to these sort of blue guys down in here. And what that does is so amazing. It causes this thing to act like almost like a merry-go-round, and this starts spinning. This thing moves as those protons start coming through over here. And as that spins, deep inside here is this funky little thing that’s referred to as a ‘rotor’. This rotor itself start spinning and notice…I put a little blob out the side right here when this rotor moves through these three different blobs. We’ve got the green, the yellow and the orange as this thing moves through these three spaces. As it keeps going through these three spaces, different things happen. Let’s say over here on the yellow one, this is where ADP + P can come in and bind…they enter over here. And then the rotor moves and will change the shape of this. And at that point, it’s gonna make it so that this ADP and P end up really close together and we’ll show what that looks like over on this side. So, so close together that they’re able to form a bond between them. And then when we get over to this side over here, that’s where, what is now an ATP is going to be released and it can flow out of it. So each of these blobs right here is going to be able to take on a different shape depending on where this rotor is, as it does, it’s circling around because of these H+s that are flying into it, over on this side, are causing the merry-go-round part to go around. It’s complicated, but just amazingly cool, and that is what allows this gradient here to contribute to the synthesis of ATP.
All right, let’s summarize: We’ve got the big combustion reaction that happens slow, and that is how we’re able to get energy. The electrons from this redox are passed through various complexes, which are really these little redox centers that are throughout the electron transport chain. And then as that happens, the protons are going to get pumped into that inner membrane space. And then as those protons returned to the matrix, that’s how ATP is going to get synthesized.
Alright, we love you guys! Go out and be your best self today and as always happy nursing!