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welcome to the next lesson in the dirty medicine biochemistry series in today's video we're going to talk about something called oxidative phosphorylation this is probably better known as the electron transport chain when we left off this is what we had discussed so far glucose can undergo glycolysis to become pyruvate pyruvate can also go back up to glucose through gluconeogenesis pyruvate can take one of four metabolic pathways the most common destination for pyruvate is to be turned back into acetyl co a acetyl co a can then go through the TCA cycle also known as the Krebs cycle to generate nadh and fadh2 when we had left off I told you that these were incredibly important byproducts and this video today will explain why nadh and fadh2 will go on to be used in a set of redox reactions that transfer electrons in oxidative phosphorylation to generate massive amounts of ATP so in today's video we're going to talk about oxidative phosphorylation also known as the electron transport chain in this video there's going to be some dirty demonics so turn off the video now if you're easily offended and by the end of this video you'll understand everything that you need to know about the electron transport chain including how electrons are shuffled through the chain how the ATP synthesis works using a proton gradient and how different electron chain inhibitors inhibit various parts of the electron transport chain we'll close the video by talking about the total ATP production in all of these biochemical pathways so that you can keep the big picture in mind with that said let's get started the goal of the electron transport chain is to couple energy stored in electron acceptors to a proton gradient that drives ATP synthesis this will become much more clear as the video moves forward to get started in this video we need to design the electron transport chain so you have an image in your brain as to how this actually works what you see here is the inner mitochondrial membrane in the the slide the bottom portion of the slide represents the mitochondrial matrix and the top represents the inter membrane space now along this inner mitochondrial membrane we have a series of complexes shown here in various colors these complexes are numbered from 1 to 5 complex one is shown in blue complex 2 is shown in light pink complex 3 in light green complex 4 in that peach color and complex 5 which is better known as ATP synthase is shown as the grey triangle on the far right additionally you have the presence of two other molecules that act not as complexes but they are embedded in this area of the electron transport chain those are coenzyme Q and cytochrome C so Co Q and cytochrome C shown there in the darker salmon color now technically these are broken into two distinct parts of oxidative phosphorylation the complex portion from one to four including co Q and cytochrome C is known as the electron transport chain because this is where electrons get shuffled from one complex to the other the ATP synthase which pumps the proton gradient to generate ATP and again we'll talk about that at the end of the video is technically known as keying chemiosmosis now it's the combination of the electron transport chain plus chemiosmosis that is together known as oxidative phosphorylation that distinction is probably not important for the purposes of exams but for keeping the big picture in mind you should know that when somebody refers to oxidative phosphorylation they're referring to this entire process but when somebody refers to the electron transport chain they're technically only talking about the movement of electrons from complexes 1 to 2 to 3 to 4 to oxygen but they're not actually talking about the final ATP synthase pump that generates the ATP now how this works is the complexes exists in the membrane and you have protons that are in the mitochondrial matrix I told you that when we discussed the TCA cycle the goal was to produce nadh and fadh2 for use right here in the electron transport chain so let's illustrate why those molecules are so important so along comes NADH and NADH approaches complex 1 NADH can give up its proton and give up its electrons and become nad plus in the process it donates its electrons to complex one when the electrons enter complex one complex one gets supercharged Illustrated here with the yellow fuzzy border when this complex gets supercharged it has the energy to pump the proton from the mitochondrial matrix into the intermembrane space as it does this it pumps more and more protons from the mitochondrial matrix into the intermembrane space and you get the accumulation of protons on the other side of the membrane this goes again from the mitochondrial matrix to the intermembrane space but this pumping is only made possible by the electron given up from NADH supercharging complex one now after a while the electron will sit in complex one and the proton gradient is beginning to form on the top in the intermembrane space you have much more protons than exists on the bottom in the mitochondrial matrix now at this point the gradient is beginning to form and complex one will pass its electrons to Co Q the electrons will go to Co Q and sit there awaiting further instruction now at this point fadh2 comes along and approaches complex 2 just like nadh fadh2 was produced in the TCA cycle it migrates here and begins its important role fadh2 can give up its electrons and turn into FA D in this process it donates its electrons to complex to complex to however cannot become supercharged and cannot pump protons from the mitochondrial matrix into the intermembrane space so the electron sits in complex 2 and awaits further instruction and ultimately gets passed to Co Q now I want to pause for a second NADH only works at complex one fadh2 only works at complex two so the electrons given up from nadh go from one to kokyu and the electrons given up by fadh2 go from complex two to kokyu now it's important to pause and understand something that's very high yield Co Q is the common electron acceptor from both complex one and complex two it's also incredibly important and very high yield to remember that NADH only gives up its electrons at complex one and fadh2 only gives up its electrons at complex two at this point the electrons are sitting in Co Q and they are passed to complex three when the electrons go from Co Q to complex three its supercharges complex 3 which creates enough energy potential to pump the proton from the mitochondrial matrix through complex 3 into the intermembrane space just like we saw when complex one was supercharged by the electrons coming off of NADH complex 3 is being super charged by the shuffling of electrons both from complex one and complex 2 2 co q to complex 3 super charging it and helping to create this proton gradient look at the slide in the intermembrane space you're getting the accumulation of protons there's a much greater positive charge on the intermembrane space than there is in the mitochondrial matrix so we're continuing to form a very big proton gradient at this point complex 3 will pass its electrons on to cytochrome C at cytochrome C the electrons arrive and then get past too complex for at complex for the electrons enter it and supercharge it just like we've seen in complex 3 and in complex one once super charged complex 4 has enough energy to pump protons from the mitochondrial matrix into the intermembrane space again the proton gradient continues to form look at the top of the slide the inch membrane space is laced with tons of positively charged protons so there's a proton gradient compared to the mitochondrial matrix which has fewer protons at this point complex 4 has the electrons sitting inside of it and it needs to pass to the final electron acceptor the final electron acceptor is oxygen the electrons are passed to oxygen which splits into two oxygen ions and protons are added creating two water molecules let's pause for a second it is incredibly high yield to understand that the final and ultimate electron acceptor and the electron transport chain is oxygen and by accepting the electrons and accepting protons two water molecules are formed everything that I just said in that sentence is incredibly important and high-yield to keep in mind when you're taking exams look at the electron transport chain complex one and complex to pass their electrons to Co Q coke you pass their electrons to complex three complex three pester electrons to cytochrome C cytochrome C pass their electrons to complex four and complex four pass their electrons to the ultimate electron acceptor oxygen which split into two oxygen ions before forming two water molecules everything that I've just said is the electron transport chain and at this point the electrons have been shuffled from one complex to the next supercharging two square complexes that you see here which are complexes 1 3 & 4 to pump protons from the mitochondrial matrix into the intermembrane space now at this point we've formed a massive proton gradient there are so many protons in the intermembrane space and so fewer protons in the mitochondrial matrix now it's at this point that ATP synthase comes into play ATP synthase is going to make use of this proton gradient to generate massive amounts of ATP so along comes the molecule ATP and ADP wants to turn into ATP which is a higher energy molecule that can be used to give energy throughout the body but in order to catalyze this conversion we have to put an enter source into this reaction because you can't just go from a lower energy source ADP to a higher energy molecule ATP without some type of energy input it's at this point that ATP synthase takes advantage of the proton gradient which was being formed by complexes 1 3 & 4 the protons will always want to flow down its gradient that is to say molecules in general like to flow from high energy states to low energy states to achieve equilibrium so protons will flow from the intermembrane space down through ATP synthase back to the mitochondrial matrix and when they do this it is an energy input that catalyzes the conversion of adp to ATP that is how the energy is formed and massive amounts of ATP are formed during that step because there's such a large proton gradient that can continuously flow downhill now as those protons come across ATP synthase they build back up on the mitochondrial matrix so they're sitting in front of complexes 1 3 & 4 ready to be pumped back up into the intermembrane space when 1 3 & 4 gets supercharged as you can see the cycle continues and the electron transport chain can continue to churn out ATP so long as nadh and fadh2 are being shuffled from the TCA cycle to the electron transport chain to continue the flow of protons now here's where we are at this point that is how the electron transport chain works and that's how electrons are shuffled along this membrane now what's important for the purposes of exams and what's very high yield to know is what drugs and what molecules inhibit each of these steps now I've drawn them here on the slide rotenone inhibits complex one anti Meissen inhibits complex 3 cyanide and carbon monoxide inhibit complex 4 and cytochrome C o Lego Meissen inhibits ATP synthase an uncoupling agent such as 2 for DNP uncouples the proton gradient and inhibits the time gradients ability to pump protons down through ATP synthase these are five electron transport chain inhibitors or five inhibitors of oxidative phosphorylation that you absolutely need to memorize not only do you need to know them by name but you need to know exactly where they inhibit the electron transport chain again I'm including this here in this discussion because the purpose of the electron transport chain is to generate ATP now we've already talked about glycolysis about gluconeogenesis about pyruvate metabolism and about the TCA cycle and at each point in these steps you generate small amounts of ATP but nothing compares to the massive amount of ATP generated in oxidative phosphorylation let's slow down take a step back and look at the big picture when we talk about how much ATP is generated at each step along the way in glycolysis you actually do form a small amount of ATP go back to the glycolysis video and look at the total net reaction you do form two ATP but you also form some NADH and NADH can be used in the electron transport chain as you've seen today so from the ATP itself in glycolysis you net two ATP but from the NADH that can go on to be used in the electron transport chain that can turn into 3 to 5 ATP because again it's nadh and fadh2 which are the very rich substances used to pull electrons to go through the electron transport chain in pyruvate metabolism we formed some nadh which can turn into five ATP if that NADH is used in the electron transport chain in the TCA cycle you do form some ATP but it's a very small amount it's a net of 2 ATP but where the money happens is from the NADH and the fadh2 formed by the TCA cycle which can go downstream and be used in the electron transport chain so I'm talking about what's shown in red on the slide now the TCA cycle produces 6 nadh + 2 fadh2 in one spin of the TCA cycle it produces 3 nadh and one fadh2 but the TCA cycle always spins twice so you multiply those numbers by 2 to get 6 nadh formed and to fadh2 formed now over the years biochemists have figured out that for each nadh molecule you can form 2.5 ATP's and for each fadh2 molecule you can perform 1.5 ATP this is very high yield and it's worth memorizing so looking at our equation just from the six NADH formed in the TCA cycle and the to fadh2 forms in the TCA cycle you can produce fifteen and three ATP's respectively now looking from the top to bottom of this list if you add everything up one movement through glycolysis down to the electron transport chain can generate anywhere from 30 to 32 ATP this is very high yield to know and it just goes to show you that it's the oxidative phosphorylation step that produces the most amount of ATP but that's only made possible by shuffling nadh and fadh2 from the TCA cycle and from other steps in biochemistry to oxidative phosphorylation to be used in the electron transport chain that concludes today's video on oxidative phosphorylation