all right you guys now we are on part 2 of chapter 9 probably my students least favorite chapter because you do have to have quite a bit of memorization all right so now we have gone through glycolysis or does that take place just for review in the cytosol right we went through pyruvate processing where does that happen in the mitochondrial matrix which by the way is where this next stage also takes place the citric acid cycle is also known as the Krebs cycle also known as a TCA cycle and as I just said it takes place in the mitochondrial matrix just as pyruvate processing does prokaryotes don't have mitochondria so it takes place in the cytosol what goes in the acetyl co a that you just made in pyruvate processing now am I going to ask you to memorize every single intermediate in the citric acid cycle no I just want you to know what goes in and what comes out so in the citric acid cycle we acetyl co a goes in and we get 6 NADH we get 4 co2 we get two fadh2 and we get 2 ATP or GTP so here they are telling you they're only showing you the info for one acetyl co a but again recall there are two acetyl choline molecules that go in so in the citric acid cycle also known as a Krebs cycle we get 6 nadh two fadh2 to ATP or GTP and hey we produce ATP so you must know you must know how is that ATP produced yes it's produced via substrate level phosphorylation just as it was in glycolysis so both glycolysis and the citric acid cycle or the Krebs cycle produce energy are in the form of ATP how substrate level phosphorylation ok so next slide Oh so notice I here we have the citric acid cycle again another name for it is the Krebs cycle where to sit occur a mitochondrial matrix so you see the little uncertain mitochondrion there telling you where it happens and we're only looking at one acetylcholine molecules so you have to double everything because two acetyl co a co into the citric acid cycle you in the process produce six NADH to fadh2 four co2 and two ATP or gtp did I say the two fadh2 I think I did hopefully I did and do I expect you to memorize the different steps no again just worry about what goes in acetyl co a goes in and what comes out and as I said what comes out is 6 nadh 4 co 2 2 ATP or GTP to fadh2 so of course the citric acid cycle just like the other stages is regulated but I'm not gonna hold you responsible for that information so I'll go through that skip that so here they tell you what is it that we have produced so far with glucose while we're oxidizing glucose again in my mind oxidation is feeling energy from glucose so far we have produced 6 co2 let's make sure we know where we produce 2 co2 in pyruvate processing and we produce four co2 in the citric acid cycle the Krebs cycle and they say we've produced 10 NADH let's see if that's true we produce 2 NADH in glycolysis we produce 2 more in pyruvate processing and we produce 6 in the citric acid cycle yep that's 10 and then I produce to fadh2 in the citric acid cycle so that makes sense as well and they tell me I produce 4 ATP how substrate level phosphorylation you produce 2 ATP net in glycolysis and 2 ATP or GTP in the citric acid cycle also known as the Krebs cycle now nadh fadh2 they're very important electron barriers because they're carrying electrons they're known as reducers they can reduce something the reducing agents because they can donate your electrons to a target molecule which is what they're gonna do nadh and fadh2 are going going to donate their electrons to the electron transport chain so energy cannot be created or destroyed only transferred or transformed why is this important because we need to figure out where did the energy that was in glucose where did it go well we produce ATP ATP is energy but also a lot of the energy is now in nadh and fadh2 they're your electron carriers very important with that so here's the summary so far of what we've covered glycolysis where does it take place notice I'm just saying the same things over and over again where does it happen what goes in and what comes out if ATP's produce how was it produced so just to recap glycolysis takes place in the cytosol glucose goes in what comes out to pyruvate to NADH and to ATP how is that ATP produced substrate level phosphorylation pyruvate processing this stage where does that happen mitochondrial matrix what goes in pyruvate what comes out to acetyl co a to NADH and to co2 you do not make any ATP in the stage make sure you know that next stage citric acid cycle also known as the krebs cycle what goes in acetyl co a what comes out six NADH two fadh2 there are your electron carriers are carrying a lot of the energy that was in glucose 4 co 2 and 2 ATP or GTP how is that ATP produced substrate level phosphorylation and so here what they're showing you is that we're releasing the energy that was in glucose in a bunch of small steps because if we were to release the energy and glucose all at once we would damage the cell we would probably burn that cell so instead we have a bunch of small little steps we're releasing enter in the form of ATP or an nadh or fadh2 and that's what they're showing you right there so yes where is most of the original energy that was in glucose because again energy cannot be created or destroyed only transfer transformed it's now in the electrons that nadh and fadh2 my electron carriers are carrying their ultimately these electrons are going to be transferred to oxygen member oxygen highly electronegative and oxygen is going to accept so many electrons with negative charges that is going to combine with protons to form water so we need to wonder what happens to the energy that is released as electrons are transferred in the elect in the electron transport chain we're going to use something that energy for doing something very useful we're gonna pump protons that's important we're going to pump protons into the space between the inner and the outer mitochondrial membrane and that's how we're gonna synthesize ATP in a process known as chemiosmosis so notice the word once again oxidation we're stealing energy now from NADH NADH is oxidized when it's combined with the inner membrane of mitochondria again prokaryotic cells like bacteria do not have mitochondria so this step takes place in the plasma membrane and we're gonna see that electrons are going to be transferred from one molecule to the next and the electron transport chain something's going to lose electrons becoming oxidized and then the recipient is going to become reduced when it accepts the electrons so yes we're gonna have molecules that oxidize nadh and fadh2 and these are the electron transport chain we're gonna transfer that electron as the electrons are transferred through the electron transport chain they're going to go down in energy and we're going to use that energy for something very useful we're going to pump protons into a small space and that's C and the space between the inner and the outer mitochondrial membranes I think this is an exam question you need to know what ubiquinone or coenzyme q is it's a lipid soluble non protein entity if you will and so they tell you yeah I know that's an exam question lipid soluble non-protein member of the electron transport chain and we're gonna see that some of the electron transport chain will only accept electrons whereas other components will accept both electrons and protons so as the electrons are transferred from one molecule to the next in the electron transport chain they're going to go down in energy alright why the electrons are going to be held more and more tightly until finally it's going to be oxygen that ends up with all the electrons and as we saw in an earlier slide oxygen will become so electronegative by being stuck with these electrons with and their negative charges that it will combine with hydrogen to form water alright so as the electrons gets transferred in the electron transport chain we're going to go down in energy we're going to release small amounts of energy what are we going to do with that energy super important that you know we're gonna pump protons into the intermembrane space the electron transport chain has four protein complexes one through four and it is Q ubiquinone and cytochrome C that transfer electrons between these complexes at the end as I said oxygen will end up with the electrons it will become so electronegative it will combine with protons to form h2o or water so here is the electron transport chain notice what they're showing you nadh fadh2 who are they my electron carriers will donate their electrons to the electron transport chain and notice that what's going on on the y axis they're showing you that we're going down in energy what are we using that energy for we're going to pump protons we're into a space between the inner and the outer mitochondrial membranes who's going to end up with all the electrons at the end oxygen will will become so electronegative it will combine with water to form I mean it'll combine with protons to form water and so they're showing you that NADH will donate its electrons to FMN which is a flavin containing prosthetic group flavin mononucleotide whereas fadh2 will donate its electrons to an iron sulfur complex alright so do I expect you to know all of these on here no just know about Q or ubiquinone alright I want you to know about you ubiquinone so again very important that you understand what are we doing with the energy that's being released as electrons are transferred in the electron transport chain we're going to pump protons into a space between the inner and the outer mitochondrial membrane so now we have a proton electrochemical gradient what does that mean we're gonna have a buildup of protons and yes you must know what a proton is it's H+ we're gonna have a buildup of protons in one small area so notice in this diagram we have a bunch of protons H+ in the intermembrane space that's going to form an electrochemical gradient those protests are going to want to diffuse down their electrochemical gradient they have a charge though so because they have a charge they're going to have a very difficult time going through the membrane so instead they're going to have to go through an enzyme known as ATP synthase and it is the enzyme ATP synthase that synthesizes ATP so notice you already see the whole picture with the EPC this is a eukaryotic cell because I see that we have the inner and the outer mitochondrial membrane there's nadh fadh2 who are they they're my electron carriers they finally donate their electrons to the etc' there's queues shuttling those electrons between the different complexes in the e.t.c notice that as electrons get transferred the electron transport chain they are going to go down in energy what are we going to use that energy for we're gonna pump protons into that very small little space between the outer and the inner mitochondrial membrane those protons are going to want to diffuse down their electrochemical gradient they have a charge so they cannot simply go through the membrane they're going to have to go through an enzyme called ATP synthase who ends up with the electrons at the end oxygen does become so electronegative it'll combine with protons to form water and you see water all the way at the right of these of this figure alright so what is the enzyme that synthesizes ATP ATP synthase it looks like to me like a lollipop it has a stuck in a knob unit alright and so it will synthesize ATP from adenosine diphosphate and inorganic phosphate so again those protons are going to be built up on one small portion of the South they're going to want to diffuse down their electrochemical gradient they have a charge a plus charge they cannot simply diffuse through the membrane they can only go through that protein ATP synthase which will actually spin as the protons are going through it producing ATP in the process so yes we have in 1961 they tell you that Mitchell proposed that the electron transport chain is used to pump protons from the mitochondrial matrix to the intermembrane space the space between the outer and the inner mitochondrial membrane ATP synthase the enzyme will use the flow of protons through it to produce ATP from ADP and inorganic phosphate and this is known as chemiosmosis alright ATP production is very dependent on this proton motive force what does that mean we have a whole bunch of protons stuffed into a little space they want to diffuse down their electrochemical gradient they can only go through ATP synthase that enzyme will actually spin producing ATP from ADP and inorganic phosphate and again you need to know I produce ATP here in fact most of your ATP is produced in the stage in the electron transport chain most of your ATP is produced right here and we need to know that this is performed via oxidative phosphorylation very important you know that so here is ATP synthase the enzyme that synthesizes ATP from inorganic phosphate and adenosine diphosphate so in your textbook they say that this is similar to what happens in hydroelectric power plants where in those plants like Hoover Dam the flow of water over these giant turbines this giant screw looking things well so the flow of water will force these turbines to spin producing electricity from the flow of water in cells we don't use the flow of water we use the flow of protons through the enzyme ATP synthase so the enzyme ATP synthase would be like these giant turbines that produce energy not in the form of electricity but here in the cell in the form of ATP I'm gonna skip through this experiment but they tell you what is it that ATP synthase looks like it looks like a it has a knob in a base the knob unit is the f1 unit and the base unit is the f0 unit they're connected to each other by a shaft and held together by a stutterer the f0 unit will turn as protons flow through it again the idea here just like in Hoover Dam where the flow of water is produced and it is used to produce energy in the form of electricity and the cell we're going to use the flow protons instead of talking about turbines is going to be ATP synthase the flow of protons through ATP synthase will be used to produce ATP from ADP and inorganic phosphate once again you need to know how is ATP synthesized oxidative phosphorylation and here's the real good figure of the enzyme ATP synthase it's got the base unit and the knob unit the f0f one unit notice all the protons pumped into a very small area between the inner and the outer mitochondrial membrane they want those protons want to diffuse down their electrochemical gradient they have a charge it's very difficult for them to go through the membrane with a charge they can only go through the enzyme ATP synthase and as they're flowing through the enzyme the enzyme will actually spin producing ATP from adenosine diphosphate and inorganic phosphate so yes what is it that's being used to produce energy in the form of ATP a proton gradient remember we said as electrons get transferred in the electron transport chain they go down in energy why they're being held more and more tightly till in the end oxygen ends up with all the electrons and what are we going to use that energy for we're going to use to pump protons into that inter membrane space those protons will want to diffuse down their electrochemical gradient they will do so by flowing through the enzyme ATP synthase producing ATP in the process alright here's the important thing most of your ATP is produced right here in the electron transport chain if they ask you on the exam hint hint whereas most of the ATP produced you would say in the EPC and if they asked you how look at that last bullet point oxidative phosphorylation so I made ATP and I call osis I'm made in in citric acid cycle but I made it be some other process on a substrate level phosphorylation in the ETV I also made ATP in fact most of my ATP here but via a different BOCES known as oxidative phosphorylation metabolism refers to all the chemical reactions that occur in living cells the cells of your body use molecules of ATP as their primary source of energy ATP is used to perform many kinds of cellular work including pumping ions transporting vesicles within the cell and making macromolecules how does the cell produce a continual supply of ATP the answer lies in the process called cellular respiration which occurs partly in the cytoplasm and partly in mitochondria during cellular respiration a glucose molecule is completely oxidized in the process it releases enough energy to produce about 30 molecules of ATP the first phase of respiration glycolysis occurs in the cytoplasm during glycolysis glucose is broken down into two molecules of pyruvate glycolysis also generates two ATP molecules and two molecules of an electron carrier called NADH pyruvate can be metabolized in two possible pathways depending on whether or not oxygen is present in the absence of oxygen pyruvate undergoes fermentation during fermentation pyruvate might be converted into lactate as in human muscles or ethanol as in yeast but there is no ATP production beyond the two ATP molecules generated by glycolysis in the presence of oxygen pyruvate is metabolized by cellular respiration which produces a great deal of energy pyruvate is transported into the mitochondrial matrix where it's stripped of a carbon atom and combined with a molecule coenzyme a or Co a to make acetyl co a this reaction produces two NADH electron carriers acetyl co a then enters the next phase of cellular respiration called the Krebs cycle in the Krebs cycle the remaining carbon atoms from glucose are incorporated into molecules of carbon dioxide this process produces two molecules of ATP and a series of electron carriers the electron carriers essentially transport energy from glucose to the next phase of cellular respiration the electron carriers donate their electrons to a series of complexes within the inner mitochondrial membrane these complexes together called the electron transport chain used the donated energy from the electron carriers to pump protons into the intermembrane space forming a concentration gradient of protons across the membrane the protons flow down their gradient through the enzyme ATP synthase which is a membrane protein ATP synthase uses the energy released by the proton flow to produce ATP from this process ATP synthase produces a large amount of ATP around 26 ATP molecules bringing the total ATP yield from one glucose molecule in cellular respiration to around 30 molecules the initial reactions in the conversion of glucose to energy are called glycolysis we will look at the overall process in terms of energy yield and final products it may seem strange but to get energy in the form of ATP from glucose we first have to expend energy in the form of ATP during this energy investment phase 2 ATP molecules are consumed later in glycolysis a series of energy yielding reactions produce four ATP molecules and two NADH molecules the energy investment reactions cost the cell to ATP molecules but are necessary to prepare glucose for the reactions that follow the end result of these reactions is a molecule of fructose bisphosphate a six carbon sugar this molecule is the starting point for the energy yielding reactions the six carbon fructose bisphosphate is first broken down into two 3-carbon molecules of glyceraldehyde 3 phosphate or g3p these 2 molecules are then transformed by a series of reactions into two molecules of pyruvate the process yields 4 molecules of ATP and converts 2 molecules of NAD+ to NADH because 2 ATP molecules were consumed in the energy investment phase the net yield at the end of glycolysis is 2 ATP molecules the fate of pyruvate after glycolysis depends on the metabolic state of the cell the presence or absence of oxygen determines the metabolic state consider the metabolism in your muscle cells at rest or during light exercise when oxygen is plentiful pyruvate enters the Krebs cycle and continues to be metabolized through cellular respiration during heavy exercise your lungs and circulatory system can't transport oxygen to your muscles rapidly enough to keep electron transport chains active the lack of oxygen forces a shift in energy metabolism toward the anaerobic pathway fermentation in muscle cells fermentation results in lactate production in some organisms fermentation produces ethanol and carbon dioxide through glycolysis muscle cells convert ADP to ATP and nadph for glycolysis to produce more ATP the cell must replenish its NAD+ supply when oxygen is present this occurs by cellular respiration but when oxygen is absent it occurs by fermentation fermentation converts pyruvate to another compound such as lactate using NADH this reaction produces nad Plus which can then supply glycolysis if fermentation continues long enough lactate accumulates the accumulation of lactate is one reason strenuous exercise makes your muscles sore notice that glycolysis produces two ATP molecules but fermentation produces no additional ATP molecules another fermentation process you're probably familiar with results in the production of ethanol and carbon dioxide from East humans have used the products of this natural fermentation process for centuries the ethanol produced during fermentation of yeast is used to make beer and wine and the carbon dioxide gas is used to make bread rise both yeast and your muscle cells need to regenerate NAD+ to continue glycolysis the two cell types use slightly different sets of chemical reactions to produce the same result the pyruvate molecules from glycolysis are transported into the mitochondrion each pyruvate then enters a two-phase process the formation of acetyl co a and the Krebs cycle a pyruvate molecule is first joined to a co a molecule in this reaction carbon dioxide is released and NADH is formed the third product is acetyl co a which contains the remaining two carbon atoms of pyruvate bound to co a this becomes a substrate for the later reactions of the krebs cycle the acetyl group now a two carbon remnant of the original glucose molecule enters the Krebs cycle the krebs cycle is a series of reactions that remove electrons donating them to the electron carriers NAD+ and fa d to form nadh and fadh2 these carriers will contribute their electrons to an electron transport chain that will then generate significantly more ATP than is produced by the krebs cycle the two carbon atoms contributed by acetyl co a are each converted to carbon dioxide thus every carbon atom from the original glucose is ultimately incorporated into a carbon dioxide molecule finally one molecule of ATP is released for each pyruvate molecule that enters the Krebs cycle because each glucose molecule contributes to pyruvate molecules the Krebs cycle generates a total of two ATP molecules for each glucose molecule metabolized the electron transport chain and the enzyme ATP synthase participate in the final phase of cellular respiration electron transport the earlier phases provide energetic electrons in the form of the electron carriers nadh and fadh2 here you can follow the fate of electrons donated by nadh the electrons are passed to the first carrier in the chain and then moved down the chain losing energy as they go the energy is used to pump protons across the membrane into the intermembrane space this creates a proton gradient that is a source of potential energy the last electron acceptor is oxygen which reacts with the electrons and protons to form h2o or water the bonding of oxygen with electrons and protons is the reason cellular respiration depends on oxygen and works only under aerobic conditions ATP synthase allows protons to diffuse across the membrane down their concentration gradient it uses the energy released by the flow to synthesize ATP from ADP and inorganic phosphate let's examine the total energy generated by cellular respiration the total includes the ATP from glycolysis the NADH from glycolysis the NADH from acetyl co a formation the ATP from the Krebs cycle and the nadh and fadh2 from the krebs cycle from the energy of all the nadh and fadh2 molecules that enter the electron transport chain approximately twenty six ATP molecules are produced so cellular respiration yields a total of approximately 30 ATP molecules much larger than the yield to ATP molecules from the partial oxidation of glucose by fermentation now not everything uses oxygen as the final electron acceptor if you do use oxygen as your final electron acceptor this is known as aerobic respiration but there can be other electron acceptors other than oxygen such as nitrate sulfate carbonate and when you don't have oxygen as your final electron acceptor then this is known as anaerobic respiration without oxygen but this is important if you want to produce the most ATP you want to have oxygen serve as your final electron acceptor why it's very electronegative recall at up electronegativity it's the tendency to hold on to electrons there's a large difference between the potential energy of a reduced electron donor and water and that translates to more energy that can be produced via that proton motive force fermentation does not take place in the presence of oxygen alright we're gonna see that in fermentation something other than oxygen accepts your electrons now let's say you're working out really really hard and all of a sudden you feel that burn you know y'all hear about you feel the burn feel the burning your muscles what's happening there your some of your cells are performing lactic acid fermentation so the idea here is that you've been working out so hard that you used up the oxygen so it's life threatening to do this because here's the thing and I think this is on the exam you need to regenerate NAD+ all right why do you need NAD+ because hey you produce nadh in glycolysis for that you need nad plus you produce NADH and pricing for that you need nad plus any place that you produce NADH means that you need it to have any D plus going in and NADH it's job is to donate its electrons to the electron transport chain who finally ends up with the electrons oxygen does but you've worked out so hard again that you have no more oxygen to serve as your final electron acceptor this is life-threatening we need we must regenerate NAD+ for the earlier stages where I produce NADH so something else has to accept those electrons so if it's not oxygen it's got to be something else all right in fermentation again we need to regenerate NAD+ we need to have NADH donates electrons to something else and so your cells will perform lactic acid fermentation where it is pyruvate which will accept the electrons and thus regenerate NAD+ other organisms perform alcohol fermentation where it's something else another organic molecule that accepts the electrons but in both cases it's super important that we read regenerate NAD+ again this can be life-threatening and so in the in the meantime what's your body doing when when it's run out of oxygen you're feeling the burn notice that you're probably breathing like this like you're breathing hard your body's saying get oxygen get oxygen get oxygen because you need that final electron acceptor so here's a comparison of cellular respiration and fermentation notice that fermentation does not have the citric acid cycle does not have the et Cie what's the significance the et Cie is where cells produce the most ATP so for this recent fermentation produces a lot less ATP than cellular respiration does we produce only two ATP molecules and fermentation versus cellular respiration so yes as we said your your muscle cells may run out of oxygen when you're exercising super hard so they will switch tempera temporarily to lactic acid fermentation why you need to regenerate NAD+ any place that you produce NADH requires nad plus to go in so the idea is your body used up its oxygen your breathing super hard trying to bring in more oxygen so you can stay alive in the meantime we're gonna produce ATP and we're going to switch to lactic acid fermentation alright so your muscle cells are breathing super hard you're trying to get more oxygen lactate you know that that so lactic acid is going to be converted back to pyruvate that's the burn that you feel in muscles so here's lactic acid fermentation idea is yourself you were working out so hard your cells ran out of oxygen we need to regenerate NAD+ so who's going to accept my electrons when there's no oxygen around in this case notice pyruvate will accept the electrons that's great when pyruvate accepts the electrons from NADH I'm able to regenerate NAD+ in the process I produce lactate or lactic acid that burn right some cells can perform a very useful process known as alcohol fermentation in this case pyruvate is converted to acetaldehyde and co2 same thing in fermentation there is no oxygen who's going to accept your electrons then in this case an alcohol fermentation is acetaldehyde that is sex electrons from NADH why is this good well when acetaldehyde accepts the electrons I regenerate NAD+ and I produce ethanol which by the way it's a byproduct the cells don't really care about ethanol but we sure like our wine or cocktails our beer our champagne in the process you also produce co2 by the way the bubbles in beer the bubbles in champagne those are co2 bubbles that are produced during alcohol fermentation when you're baking bread with yeast what makes the bread rise its the co2 gas that makes the bread rice and so we can thank fermentation for valuable products like soy sauce tofu love tofu yogurt cheese chocolate would not take like taste like chocolate until it's fermented and so there are prokaryotic cells like e.coli that live in our intestine our large intestine and they perform fermentation only so here's alcohol fermentation notice that again we are regenerating NAD+ by having an organic molecule except electrons from NADH in this case electrons are accepted by acetaldehyde in the process we produce ethanol in our cocktails and co2 again the bubbles and champagne the bubbles and beer the bubbles that make bread rice now just as I said fermentation is a lot less efficient than cellular respiration because you only produce two ATP per glucose molecule why so little there is no EPC there is no Krebs cycle and fermentation in cellular respiration we produce about 29 ATP per glucose now there are some organisms like e.coli that are facultative anaerobes they can grow with or without oxygen so they can switch between fermentation when there is no oxygen and aerobic respiration when there is oxygen but guess what they'd rather grow with oxygen because you can produce a lot more energy with oxygen then you can when there's no oxygen available so it seems overwhelming it seems like a lot of memorization honestly it is but it that's all there is if you memorize it it's just the same thing over and over again again you must know what goes in I just worry about what comes out if I know what comes out then I work backwards and no it goes n you need to know where these stapes steps take place you also need to know where ATP is made and if ATP is made then how was it made by substrate level phosphorylation or oxidative phosphorylation all right you guys good luck this video is extremely good at just summarizing everything that we've covered so far