e e all right good morning to everyone welcome to the zoom um I have haveed this week to doing thank you okay a lotted this week to doing the rest of cellular respiration um and you will be doing the photosynthesis and realize it on your own um it's just a realiz for photoes okay so so you have a two realiz it's to do in this unit one over cellular respiration and one over photosynthesis so last time we were talking about the introduction to a lot of definitions that we use in cellular respiration and cellular respiration is making energy in cell that's basically what it is and so the first part of cellular respiration is glycolysis so glyco represents glucose and Lis represents breakdown so the breakdown of glucose that's what we're going to be talking about why do we do it so the first realiz it is chapter nine and the other one is chapter 10 it'll say photosynthesis which then is chapter 10 so why are we doing glycolysis because glucose gets broken down it literally gets cut in half into a three carbon molecule there are literally two three carbon molecules and those are are modified a little bit and called pyate okay we add a little bit of vitamin A to run the next cycle then we make these because they will run the next cycle that happens so what happens glucose the carbon sugar is split into two three carbon molecules of pyate okay there we go now this is showing up what goes in glucose so what is the substrate in glycolysis it's glucose what are the products that come out to ATP which we make by substrate level phosphorilation and last time we gave a definition of that we said this is when you make substrate level phosphorilation substrate level phosphorilation is H this machine has such problems trying to translate um it is when you make ATP energy in regular chemical reactions okay so you're going to make out of this reaction glycolysis 2 ATP two pyate which are the three carbon molecules and two nadh we said last time nadh is the energized form it has potential energy okay my husband has a meeting going one and there's a riot happening in that room so nadh is you said it's the potential energized version of ATP she left for a minute sorry gotcha okay sorry my husband has a meeting going on in the in our library room and there's all kinds of noise coming out of there which I wasn't sure you could hear so I'm sorry I was just asking so nadh is the like you said it's the potential energized version of ATP no so it's okay so let's go back here a minute so whoops so this is NAD and nadh these are basically a a form of B vitamin and they're hydrogen carriers so NAD we talked about reduction in oxidation oxidation you're going to see it lacks the hydrogen in reduced forms that carry potential energy they're going to have the hydrogen this is the oxidized form it doesn't have the extra there's the extra hydrogen you don't have to memorize these structures but so nadh is a hydrogen carrier and literally what it's going to do let's keep going here it's gonna carry this energy over to the last step of cellular respiration and then we're going to see how it unlocks energy the reason why you make nadh and this is potential energy at this point you can't use it in this form but you will be able to use it in the electron transport chain two two doors down um and the reason why you do this is because when you make this potential energy nadh that Bond on that hydrogen when you break those one nadh will give you three ATP so you get more energy out of it than directly make an even ATP does that kind of help a little bit yes thank you okay so you can't use the nadh right now it has to be sent to another cycle but when you get it there it's going to make a lot more energy yeah sorry all right so this is glycolysis we take s these are all carbons here one two 3 four five six um first we add energy and then we break it apart into these py three carbon molecules and now we give off energy but if we look at this we make four we make four ATP we're looking at net reactions we used 2 ATP that's why we say we make the net of 2 ATP because you have to subtract what you used okay okay so we said again up in web courses we have something called Etc chart which is just not the electron transport chain which we haven't gotten to yet it is a chart of every single thing glycolysis the KB cycle the electron transport chain and it tells you what goes in what goes out why do you do it what's the main thing what's the waste product so there are 10 steps involved in this glycolysis we're not going to ask you to know every single step but because enzymes are specific every step has a separate enzyme okay um we only make this tiny little amount of energy the reason why we do glycolysis again is to get the pyrates which are going to turn the next cycle the crb cycle is going to be run on py ofate so we need that to keep this going the first five steps require energy input in glycolysis steps 6 through 10 make the ATP okay so we gain to ATP Again by regular chemical reactions this is what really happens we're not going to ask you to memorize it but here we start to energize once we've energized the glucose we're going to snap it in half okay that's the first five steps second five steps then we actually start to make isomers of it and then we end up with energy and nadh and some other stuff that you've never seen before that you don't have to worry about okay so after glycolysis but before a cycle called the KB cycle which is part two we have to process the pyy it's like when I was first married I had been in school my whole life I had no clue how to cook and I kept feeding my husband's spaghetti like for a month and he was so nice he didn't say anything until finally after a month I saw him starting to put ketchup on the spaghetti and my husband puts ketchup on stuff he doesn't really like to eat except for hamburgers so at that point I knew I needed to do something different so this aceto COA reaction is kind of like putting ketchup on the pyate it kind of you you take vitamin A and you put it on the pyate to make it acceptable for the next cycle to basically metabolize it so both of these pyrates are processed and turned into something called a cetal COA they're processed one at a time we're going to show you this we were we made we did glycolysis in the cytoplasm the crb cycle takes place in the mitochondria Matrix which is kind of like the jello part of the mitochondria and so we have to transport these pyes through the mitochondria membrane so there are Transporters of the mitochondrial membrane and they are kind of strange Tom transporter of the outer mitochondrial membrane there are two of them so like there's an inner and outer membrane right so these are the membranes so this would be transporter of outer membrane Tom to get the pyate through the outer membrane and then transporter of inner membrane Tim Tim and Tom they transport pyate they can transport some other things they are active Transporters and you know what that is they require energy but these things are Moody these things are just so interesting to look at that there are labs in Europe that have as many graduate students as there are people in this class and they're looking at these things because even though we call them active Transporters sometimes they do use energy and sometimes they don't they're really moody sometimes they'll use two ATP per pyate sometimes they use one ATP ATP and sometimes they use no ATP but we still call them active because at some points they are using energy they are the weirdest Transporters in the world we're trying to understand how they do this because if we can figure out how they do this we'll be able to do a lot of things imagine being able to levitate things through your membranes um they use a special process they have special special skills which are too advanced for us to talk about here when they levitate things through okay so Tim and Tom are the Transporters of the mitochondrial membrane and they basically are very different okay so again let's review the mitochondria it's kind of shaped like a bean I have a question yeah go ahead I have a this is kind of a Sidetrack question but is there any way we could like consume ATP to get more things done within the body so that's a really good question and um if you did that it would probably be broken down in your digestive tract so unfortunately we can't do that but it's it would be great if we could so we have inner and outer m membrane inner outer and then the extension um it'll get degraded ATP doesn't last long when you make it um so these are the chrisy the inner infoldings of the inner membrane and all this around here is the jello which is the Matrix Su so mitochondria have an outer membrane you have an inner membrane they have infoldings of that inner membrane called the Christi between the inner and outer membranes there's a space so literally if this is like in your house this is the ceiling in your house en this is the roof this is your attic right your crawl space up there te same way with your mitochondria membranes this is the inner membrane this is there's a space in here this is called the intermembrane space and boy is it important this is where when we're when we get to part three of cellular respiration like everything happens this is where the action is you have to have a lot of hydrogen this is super acid it's super acid in here acid lots of hydrogen H+ ions in here this has to be acid if we lose acidity here we're done in three minutes okay and then the Matrix is kind of like the jello and then the Transporters Tim and Tom so there are a lot of parts to the mitochondria this is why we started talking about it last [Music] time sorry my cat just like reached over and grabbed my hand and sunk his teeth into them lightly um um wants to play and I'm like no not now so each PIR is pulled into the Matrix one at a time if you and I I don't think they have these in Department Stores um like in in New York at least they have these glass doors they also have them in some areas of cruise ships they're they're like glass doors that circle around and they little compartments and you go into a compartment and push the bars you know and you keep walking and the door rotates that's kind of how this works with each glucose being pulled through and then going around one at a time okay we're going to talk about how this happens revolving doors yes okay so we're going to look at a picture because pictures are necessary here so here's the outer m here's the infolding of the inner membrane this is the chrisy here is the cytoplasm now cytoplasm is also known AKA cytool right so here is the pyate three carbons and all the other stuff there's the carrier protein that pulls it through Tim and Tom and then we're in The Matrix The Matrix is the green the yellow is the inner membrane the Christi then we go through this acetal COA reaction we literally chop off CO2 which is a waste product right because you're breathing it out and then we literally as we break that Bond we make nadh you will see nadh listed as nadh plus H+ it's how it's carrying all of its protons and electrons and don't worry about it we'll say it is either nadh or nadh plus h if you see nadh it's the potential energy form right this is acetal COA so we chop off a CO2 and we add some vitamin A this SC COA this is literally vitamin A so you're getting the concept that you know nadh is a B vitamin and COA is an AV vitamin and vitamins are really important in making energy this is why you should have enough of them now this was the pyate it's now an acetyl COA and then you'll pull the second one through and do the same thing this is ready now to go to the next cycle the next cycle is called the crb cycle it has three different names actually um pyy would not be acceptable to the next cycle unless it was chemically modified questions yet so is the pyrovate reacting with the nadh or the NAD and then turned into nadh actually reacting with enzymes and vitamin A the nadh is there waiting to get the hydrogen when the bonds are broken does that help yes that does help M okay so now we're going to start to talk about the KB cycle which again why they do this in science they give everything five different names kreb cycle named after the guy KBS who found it is the second to True phase of cellular respiration has multiple names citric acid cycle or TCA cycle TCA is tricarboxylic acid cycle um it occurs in the Matrix of the mitochondria why do we do it we want to produce a lot of what we call reduced that means they have H+ reduce means they have H+ energy carriers in intermediary is a carrier an intermediary shuttle the hydrogen from one reaction group to the other so what our goal of the crb cycle is we want to produce a lot of the potential energy carrier nadh and the potential energy carrier fadh2 fad is another type of B vitamin um we I might use the other names so again you may want to have them written on your note card um for every nadh that you make in the KB cycle later on when we go to the last phase of cellular respiration we go to the last phase not this right now doesn't help you but later when you can unlock it every one of these equals 3 ATP and every one of these will equal 2 ATP this is like going to a sale and get more bang for your that's why you do it okay so these are the potentially energized substances so even though in the CB cycle we do make a pathetic amount of ATP um you know it's it's a small amount and so we'll take ATP when we can get it but okay so the goal is oxidation of these organic molecules these carbon based molecules to create the the potential energy nadh and fadh2 it's in the mitochondria Matrix what goes in what's the reactant or this acetal COA one molecule at a time it goes in that used to be the pyate and we added vitamin A and cut off CO2 so from one [Music] glucose that made two pyate that turned into two acetyl COA this turns the KB cycle twice the KB cycle turns one once for every acetal COA and you made two acetal COA out of the glucose that came from glycolysis turned into the two pyrates we added the vitamin A right this is a lot so from two turns of the crb cycle you will get six nadh two fadh2 two ATP which is a pathetic amount of ATP you can't run a yeast on that and Co 2 is a waste product so we're going to tell you now for the first time that there is a waste product in it's CO2 um in your reading in glycolysis in your reading you may see water as a waste product ignore that we're going to say we don't have waste products in glycolysis so this is our first waste product that we're going to recognize see this is why you're breathing out CO2 right now you're doing this and um we're going to explain that you know in every cell you're running this running this running this so you know you don't just make two ATP you make two billion ATP so now we're talking so here we go um um you said we make six nadh plus and 6 ATP those are the waste products so you make six ndh two fed and two ATP per turn of the crab cycle for I'm sorry per two turns per turn you make one um one FH one ADP and three [Music] nadh did that answer your question wait can you repeat the last thing you just said yeah I'm gonna I'm gonna show you okay so here you know again have a question to wouldn't it be um four fadh since it makes two ATP nope because they're they're not related so I'm going to show you this and then I'm going to show you how it really happens I need to put this somewhere okay there so this is the pyate this it turns into a ceto this starts out that's why they call it citric acid cycle you do not have to memorize all these but okay let's look at the places where we make this this is one turn now we had two py they're going in one at a time here comes the first one in number one pyate going in um it gets turned into a cetto CO one 2 3 nadh okay so for one turn I'm going to do this in pink from one turn we have three n a DH we have one fadh2 and we have one ATP that's from one turn of KBS but we had two pyrates so the second pyate this is number two py8 now we have three more n a DH because you know again every time we do this we get three nadh we get one fadh2 because of the chemical reactions and we get one ATP so when you add up all the turns from the two pyrates that turned into the two aceto coas that came from the one glucose you get three plus + 3 is six this is total n a d h you get 2 f a d H2 and you get two a t p everybody's like [Music] OMG so does the co just go down as well and yeah and the CO2 you literally get um you can see where the CO2 tws come off you literally get four CO2 but we're not going to even go there yeah the CO2 like you know is coming out as you're cracking you're cracking carbon skeletons and carbon in two oxygens comes out here here here and one other place that they're not showing so this is the KB cycle but it runs two times separately per pyate that turn turned into percoa this is number one and then number two goes through go ahead so the two um nadhs and the two atps that were produced in glycolysis those are the like um nadhs and the ATVs that are used to run the cycle like before the oh uh yeah this okay these nadh's and fadh Es are produced by substrate level phosphorilation by chemical we're going to show you this in a minute the picture is going to blow up your mind but um these are potential energy that are going to go to the third cycle the whenever you make ATP it's ready to be used and you can use it for whatever right away does that help so these these have to go to these there's only one place that can unlock this potential energy and and that's called the electron transport chain and it's really bizarre and interesting does that help other questions do you so you don't want us to know how many I can't hear you I heard is there ever hello do you want to try to ask again I heard is there ever and that's all I heard you want to try to type it into the chat I can't hear you at all okay so I'm going to keep going if you have a question just turn your mic back on please um so why did we say there was six nadh two fadh and 2 ATP but you just saw three nadh one fadh and one ATP because it depends on the number of turns of the crb cycle and why do we say nadh and fadh are reduced because they gained hydrogen which is potential energy they got reduced reduced means they gained hydrogen or electrons questions about this stuff and then I wrote the answers down here for you okay the next slide is going to blow everybody up I know it is now I don't want you to panic when you see this we're going to show you the actual CB cycle The Originators of the diagram forgot you haven't had biochim yet this is the crmp cycle this is a cocoa coming in this is this is why we call it citric acid cycle citrate is citric acid okay then you add water hydrolysis and then you get isocitrate and here the first NAD comes out then you get alphao glate then the second nadh comes out then you get suxin and then you eventually get ATP here and then you get ferate and that's where you get fadh between suxin and fumerate and then you get malate and then from malate to oxil oate these are all organic chemicals um and we call this a cycle because then when when you get alxo acetate the acetyl COA comes back in and you generate citrate again you do not have to memorize this diagram but this is what's really really happening and the CO2 were coming off there's two that come off up here and two that come off down here okay so this is a process um this do this is very sensitive to certain poisons okay um to let you know there was a very famous scientist that worked for one of the World Health agencies and he went home to the Outback he lived in the outback somewhere um and when he went to visit the people in his village he was horrified to find that they had like black dots All Over The Souls of their feet and the palms of their hands and he recognized that as terminal arsonic poisoning arsonic is a heavy metal arsonic interferes in the KB cycle and in many other things he he was horrified as he visited other Villages he saw the same thing and so he started to investigate the situation and he found that um in trying to be helpful to these Villages one of the you know Global World organizations has had put pable drinkable water wells down into these Villages and unfortunately what they discovered um in order to get more bang for their buck and and put more wells in they didn't test the soil because arsic is something that usually comes from industrial pollution they didn't have industry in these places they didn't expect arsenic but down in the soil deep in the soil there were layers of of high arsenic areas that were natural and these people were getting poisoned by the water so arsenic is one of the things that can interfere with the crab cycle it's the teardrop marking stri yes exactly and um you know then the World Health agenci flipped out of course because once those people had those markings on their hands that meant it was already they were already going to die I mean if they didn't feel bad yet it was coming um and so they had to put scrubber systems into those Wells and it wasn't just one Village it was 10 or 15 Villages it was it was a disaster so um if you are going to be a scientist working for one of these organizations you have to insist that they follow proper procedures and not cut Corners even though they were trying to do it for all the best reasons because when they did certain testing that was going to cut down a number of Wells they could put in but you cannot cut Corners so you said aric it like what does it do to the CP cycle so arsenic actually it interferes right here at step number six not you don't need to know that but yeah it actually goes in there and binds to an enzyme here and then you're done okay so in summary from the CB cycle from two turns which was from two acetal coas which was from one glucose eventually way back in the day we got total of two ATP six nadh and two fadh that came from one glucose it started the process CO2 is the waste product you may not know this but every person has breath prints like so in forensic science when they're trying to catch criminals every person has breath prints that are just like fingerprints your CO2 breath print is individual to you or to any other animal um these cycles that we're talking about occur in all mammals so your cat does this your dog does this whales do this horses do this um we all do this and we're all then vulnerable to the same types of poisons and things so the crb cycle so from glycolysis do we make fadh no fadh 2 is only made in the KB cycle nadh is made in both glycolysis a little bit and the KB cycle much more in the KB cycle questions yet everybody's so quiet it's woring [Music] so yeah there are like when when kids get into lead there are things also that it does um to their whole body and there are these things called keading agents which they can try to unbind heavy metals with I am full of heavy metal because I the kind of chemo you know for those of you that don't know I'm a cancer survivor I had to have chemo 10 years ago and then two and a half years ago again for a different kind of cancer believe it or not um and I had to have heavy metal chemo both time so I have heavy metals just all over my body um and my kidneys really did not like that the second time and started to say no but I'm I'm doing good now so penil is is it like diluted so say that again is what diluted pencil Le pencil Le okay so pencil lead is um yes it's it's a little bit it's not like heavy pure lead um it's they they do a little bit of they do a little bit with the carbon in it but I mean you still don't want to eat it or anything they used to use lead to sweeten water yeah it's graphite it's like it's not like PB lead in the periodic table it's diluted a little bit yeah I'm sorry say that again somebody asked another question no I just said they used to use lead to sweeten water oh that was a disaster yeah lead causes you know neurological problems and all kinds of other problems in children and unfortunately we have some cities in the United States that for years have been having problems with because they have lead pipes they have lead in their water and it's taken forever to change the systems out which is just ridiculous okay other questions so questions about glycolysis or the CB cycle youbody so quiet this is something that you do need to kind of sit and look at and you know um of course you don't want to take the chapter nine quiz until we're totally done chapter nine um and chapter nine quiz is only over chapter nine that's solely what it's over because chapter nine is the most complicated of of what we're doing right now explain glycolysis okay so the electron transport chain is the third and final step but somebody ask can we recap glycolysis so let's go back there for a minute glycolysis is basically when we're going to break down glucose we're going to take glucose of six carbon sugar and break it into two pyate molecules then in the aceto COA reaction we're going to put some vitamin A on it so it look it's it happens in the cytoplasm and we're going to literally crack in half we're going to take glucose and crack it in half and then we're going to modify it some more to get it to be pyate so literally when we do this we are going to end up with let's go back to this we're going to end up with okay let get this up here we break the glucose in half we get 2 ATP which again is not much made by substrate level phosphorilation so far both glycol is in the CB cycle all the actual pure ATP was made by substrate level phosphorilation which means by straight up chemical reactions you're going to see when we get to the electron transport chain that the way you make energy there is not chemical reactions it's crazy stuff that goes on in there um so we make two pyate two ATP and two nadh from glycolysis and we're not going to talk about a waste product there yes go ahead sorry um so you said so pyate is modified GL glucose yeah so what Pate is is it snaap the glucose so you know glucose has six carbons and literally you just snap it in half change it a little bit and then for the aceto COA you add vitamin A to it you add you take off some CO2 and add vitamin A to both of them and that gives you aeto too yes literally you linear this thing out and snap it in half that's what you're doing does that help so it's snapped in half and then they add you add vitamin A and you you take away a and we're not gonna yeah as long as you know you add vitamin A you're good we're not you you take away CO2 but we're not going to give you all these reactions this is not like IB or something because you know I mean if you're going to if you decide that cellular metabolism is going to be your biology world and that's what you want to study um you will learn this stuff in graduate school in in at that point you'll never forget it again but you know just having to know every step that goes on walking around in life it doesn't help you what we're trying to get to is why are you doing everything and it will make much more sense when we get to the electron transport chain other questions about this everybody's like oh my gosh and of course we will at some point talk about more cellular poisons yeah there were there was lead in cans too that's true people did all kinds of stuff with lead which was not good so the third and final step of cellular respiration is called the electron transport chain or Etc and this is where we make the most energy okay this is going on in the Christi so electron transport chains are all these protein Transporters that are embedded in the inner membrane of the mitochondria I'm going to going to say that again the electron transport chain is all these protein Transporters they're like a unit they're units of them and they're repeated over and over again in the inner membrane of the mitochondria which we call the chrisy and we're going to see all this we're going to see pictures we're going to spend like a whole we're g to like spend a whole day on this next time so there are lots of proteins involved in transfer of hydrogens um and in the electron transporting the way that you're going to make the ATP is by generating a hydrogen gradient a difference in hydrogen H+ across the the membrane and we're going to see this okay um in the electron trans for chain we have a lot of names for how you make the energy okay hang on I'm gonna I'll get there I may get there next time I just have to finish this thought um so in the electron transport chain the method the name of the method we're going to use to make pure ATP it's gonna be called chemiosmotic phosphorilation it actually has three different names which we'll get to um this is the process that you you take the energy stored from the hydrogen difference concentration difference across the membrane and you use it to power making ATP there is literally a molecular machine that's involved embedded in the membrane of the inner mitochondria and input okay so okay so we make the most energy here in the electron transport chain and we're going to show you what it looks like in then okay so let's show you this picture this is one unit of an electron transport chain Don't Panic this is the machine that makes the ATP these are the trans Porters and again we're going to use every method of we're going to use active transport definition facilitated diffusion definition here's the outer membrane here's the inner membrane this is the chrisy this is the intermembrane space we're going to sequentially go through all this stuff step by step you have these this is one electron transport chain unit you have the these over and over again embedded in your mitochondrial membrane so you don't have one of these you have thousands of these in every cell and you have a billion cells in your body so this is serious energy making Machinery here just so that you can see what it looks like now let me see if okay so next time we're going to talk about the electron transport chain what does it do how does it work and then after that in the next lecture we're going to talk about what poisons can affect it again the electron transport chain is in every single mammal okay every single mammal and these Transporters make us susceptible to things like carbon monoxide okay carbon monoxide um affects not only our red blood [Music] cells but but also the electron transport CH this is why you know we are they were cautioning people before the storm came that please keep your generators outside please do not put them in the house with you it will kill you make sure they are in a well ventilated don't put them in your garage face the exhaust vent out away from everything because carbon monoxide can affect all this stuff okay so let me now look at this again there was a question I needed to answer could I explain the difference between pyruvic acid and the salt form of pyrovate so the salt okay so pyruvic let me go back here to show it to you so this is the aceto way this I can't I got to actually show you so this is the pyy in the salt um there are some ionic groups that are on here and it becomes supercharged um in when we do a when we turn it into aetoo then we lose the charge so that's one of the main reasons carbon monoxide is colorless odorless tasteless yes and that is why it's bad because you don't even know you're being exposed to carbon monoxide and you just get sleepy and take a nap and don't wake up which is horrible all right so how do you go from from uh the crab cycle to the electronic like train chain or what I forget what the name was the one after the Krab cycle is it like is there like yes a connection between the two yes and you know what the connection is the connection is the nadh and the fadh2 so literally here they come so the nadh comes out of the CB cycle cruises on over um in The Matrix this is the Matrix of the mitochondria so it was made in The Matrix It cruises on over and it cruises up to the first transporter to give up its hydrogen the fadh goes to a different transporter and so the linking factor between the KB cycle in the electron transport chain are the nadhs and fads which were going to find out are like Uber drivers that carry hydrogen they pick it up they get reduced they dump it off at the electron transport chain they get oxidized they lose it and they're circular their life is circular they go back to KBS they pick up hydrogen they come to electron transport chain they drop off hydrogen and we're going to see this all next time yes so you said the nadh and the fadh they are what links this whole system together okay and then you said those are the ones that they lose their hydrogen yes we're going to show you that these carriers are literally going to pull off their hydrogen and pump them up here okay we're gonna see all this all right well I know we're overtime so thank you for coming to the zoom next time we will talk about the electron transport chain and the Transporters and all that kind of thing any other questions I asked a question about the like
As you have read, nearly all of the energy used by living cells comes to them in the bonds of the sugar glucose. Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolism. In fact, nearly all living organisms carry out glycolysis as part of their metabolism. The process does not use oxygen directly and therefore is termed anaerobic. Glycolysis takes place in the cytoplasm of both prokaryotic and eukaryotic cells. Glucose enters heterotrophic cells in two ways. One method is through secondary active transport in which the transport takes place against the glucose concentration gradient. The other mechanism uses a group of integral proteins called GLUT proteins, also known as glucose transporter proteins. These transporters assist in the facilitated diffusion of glucose.
Glycolysis begins with the six-carbon ring-shaped structure of a single glucose molecule and ends with two molecules of a three-carbon sugar called pyruvate. Glycolysis consists of two distinct phases. The first part of the glycolysis pathway traps the glucose molecule in the cell and uses energy to modify it so that the six-carbon sugar molecule can be split evenly into the two three-carbon molecules. The second part of glycolysis extracts energy from the molecules and stores it in the form of ATP and NADH—remember: this is the reduced form of NAD.
The illustration shows a simplified process of glucose moving through the stages of glycolysis. First two A T P are added, then the glucose is split into two branches, with N A D H and two A T P being released. The net products are 2 pyruvate molecules and 2 N A D H and 2 A T P molecules. Figure 7.7 Glycolysis begins with an energy investment phase which requires 2 ATP to phosphorylate the starting glucose molecule. The 6-carbon intermediate is then split into 2, 3-carbon sugar molecules. In the energy recovery phase, each 3-carbon sugar is then oxidized to pyruvate with the energy transferred to form NADH and 2 ATP. Credit: Rao, A. and Ryan, K. Department of Biology, Texas A&M University First Half of Glycolysis (Energy-Requiring Steps) Step 1. The first step in glycolysis (Figure 7.8Links to an external site.) is catalyzed by hexokinase, an enzyme with broad specificity that catalyzes the phosphorylation of six-carbon sugars. Hexokinase phosphorylates glucose using ATP as the source of the phosphate, producing glucose-6-phosphate, a more reactive form of glucose. This reaction prevents the phosphorylated glucose molecule from continuing to interact with the GLUT proteins, and it can no longer leave the cell because the negatively charged phosphate will not allow it to cross the hydrophobic interior of the plasma membrane.
Step 2. In the second step of glycolysis, an isomerase converts glucose-6-phosphate into one of its isomers, fructose-6-phosphate (this isomer has a phosphate attached at the location of the sixth carbon of the ring). An isomerase is an enzyme that catalyzes the conversion of a molecule into one of its isomers. (This change from phosphoglucose to phosphofructose allows the eventual split of the sugar into two three-carbon molecules.)
Step 3. The third step is the phosphorylation of fructose-6-phosphate, catalyzed by the enzyme phosphofructokinase. A second ATP molecule donates a high-energy phosphate to fructose-6-phosphate, producing fructose-1,6-bisphosphate. In this pathway, phosphofructokinase is a rate-limiting enzyme. It is active when the concentration of ADP is high; it is less active when ADP levels are low and the concentration of ATP is high. Thus, if there is “sufficient” ATP in the system, the pathway slows down. This is a type of end product inhibition, since ATP is the end product of glucose catabolism.
Step 4. The newly added high-energy phosphates further destabilize fructose-1,6-bisphosphate. The fourth step in glycolysis employs an enzyme, aldolase, to cleave fructose-1,6-bisphosphate into two three-carbon isomers: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.
Step 5. In the fifth step, an isomerase transforms the dihydroxyacetone-phosphate into its isomer, glyceraldehyde-3-phosphate. Thus, the pathway will continue with two molecules of a glyceraldehyde-3-phosphate. At this point in the pathway, there is a net investment of energy from two ATP molecules in the breakdown of one glucose molecule.
This illustration shows the steps in the first half of glycolysis. In step one, the enzyme hexokinase uses one A T P molecule in the phosphorylation of glucose. In step two, glucose dash 6 dash phosphate is rearranged to form fructose dash 6 dash phosphate by phosphoglucose isomerase. In step three, phosphofructokinase uses a second A T P molecule in the phosphorylation of the substrate, forming fructose dash 1, 6 dash bisphosphate. The enzyme fructose bisphosphate aldose splits the substrate into two, forming glyceraldeyde dash 3 dash phosphate and dihydroxyacetone-phosphate. In step 4, triose phosphate isomerase converts the dihydroxyacetone-phosphate into glyceraldehyde dash 3 dash phosphate. Figure 7.8 The first half of glycolysis uses two ATP molecules in the phosphorylation of glucose, which is then split into two three-carbon molecules. Second Half of Glycolysis (Energy-Releasing Steps) So far, glycolysis has cost the cell two ATP molecules and produced two small, three-carbon sugar molecules. Both of these molecules will proceed through the second half of the pathway, and sufficient energy will be extracted to pay back the two ATP molecules used as an initial investment and produce a profit for the cell of two additional ATP molecules and two even higher-energy NADH molecules.
Step 6. The sixth step in glycolysis (Figure 7.9Links to an external site.) oxidizes the sugar (glyceraldehyde-3-phosphate), extracting high-energy electrons, which are picked up by the electron carrier NAD+, producing NADH. The sugar is then phosphorylated by the addition of a second phosphate group, producing 1,3-bisphosphoglycerate. Note that the second phosphate group does not require another ATP molecule.
This illustration shows the steps in the second half of glycolysis. In step six, the enzyme glyceraldehydes dash 3 dash phosphate dehydrogenase produces one N A D H molecule and forms 1 3 dash bisphosphoglycerate. In step seven, the enzyme phosphoglycerate kinase removes a phosphate group from the substrate, forming one A T P molecule and 3 dash phosphoglycerate. In step eight, the enzyme phosphoglycerate mutase rearranges the substrate to form 2 dash phosphoglycerate. In step nine, the enzyme enolase rearranges the substrate to form phosphoenolpyruvate. In step ten, a phosphate group is removed from the substrate, forming one A T P molecule and pyruvate. Figure 7.9 The second half of glycolysis involves phosphorylation without ATP investment (step 6) and produces two NADH and four ATP molecules per glucose. Here again is a potential limiting factor for this pathway. The continuation of the reaction depends upon the availability of the oxidized form of the electron carrier, NAD+. Thus, NADH must be continuously oxidized back into NAD+ in order to keep this step going. If NAD+ is not available, the second half of glycolysis slows down or stops. If oxygen is available in the system, the NADH will be oxidized readily, though indirectly, and the high-energy electrons from the hydrogen released in this process will be used to produce ATP. In an environment without oxygen, an alternate pathway (fermentation) can provide the oxidation of NADH to NAD+.
Step 7. In the seventh step, catalyzed by phosphoglycerate kinase (an enzyme named for the reverse reaction), 1,3-bisphosphoglycerate donates a high-energy phosphate to ADP, forming one molecule of ATP. (This is an example of substrate-level phosphorylation.) A carbonyl group on the 1,3-bisphosphoglycerate is oxidized to a carboxyl group, and 3-phosphoglycerate is formed.
Step 8. In the eighth step, the remaining phosphate group in 3-phosphoglycerate moves from the third carbon to the second carbon, producing 2-phosphoglycerate (an isomer of 3-phosphoglycerate). The enzyme catalyzing this step is a mutase (isomerase).
Step 9. Enolase catalyzes the ninth step. This enzyme causes 2-phosphoglycerate to lose water from its structure; this is a dehydration reaction, resulting in the formation of a double bond that increases the potential energy in the remaining phosphate bond and produces phosphoenolpyruvate (PEP).
Step 10. The last step in glycolysis is catalyzed by the enzyme pyruvate kinase (the enzyme in this case is named for the reverse reaction of pyruvate’s conversion into PEP) and results in the production of a second ATP molecule by substrate-level phosphorylation and the compound pyruvic acid (or its salt form, pyruvate). Many enzymes in enzymatic pathways are named for the reverse reactions, since the enzyme can catalyze both forward and reverse reactions (these may have been described initially by the reverse reaction that takes place in vitro, under nonphysiological conditions).
LINK TO LEARNING Link to Learning Gain a better understanding of the breakdown of glucose by glycolysis by visiting this siteLinks to an external site. to see the process in action.
Outcomes of Glycolysis Glycolysis begins with glucose and produces two pyruvate molecules, four new ATP molecules, and two molecules of NADH. (Note: two ATP molecules are used in the first half of the pathway to prepare the six-carbon ring for cleavage, so the cell has a net gain of two ATP molecules and two NADH molecules for its use). If the cell cannot catabolize the pyruvate molecules further, it will harvest only two ATP molecules from one molecule of glucose. Mature mammalian red blood cells do not have mitochondria and thus are not capable of aerobic respiration—the process in which organisms convert energy in the presence of oxygen—and glycolysis is their sole source of ATP. If glycolysis is interrupted, these cells lose their ability to maintain their sodium-potassium pumps, and eventually, they die.
The last step in glycolysis will not occur if pyruvate kinase, the enzyme that catalyzes the formation of pyruvate, is not available in sufficient quantities. In this situation, the entire glycolysis pathway will proceed, but only two ATP molecules will be made in the second half. Thus, pyruvate kinase is a rate-limiting enzyme for glycolysis.