Metabolism | Glycogenolysis

I engineers in this video we're going to talk about glycogen alysis if you guys haven't already seen it go watch our video on glycogenesis because we're going to really be depending upon that concept first okay so if you guys watch glycogenesis you know that we basically synthesize glycogen by the activity of the glycogen synthes and the branching enzyme right what we're going to do now is we're going to show you exactly how this glycogen polymer is getting broken back down into gluc ose but before we do that we have to understand what is this process

called whenever we're breaking down the glycogen back into glucose it's called glycogenolysis Lis meaning cut glycogen right so we're cutting the glycogen and forming glucose now once again where is this process occurring where is this glycogenolysis process occurring it's specifically occurring where in the liver and in the muscles however it can occur in other tissues too but we're focusing on the more significant ones where this is occurring okay so it's occurring where in the liver and in the muscles but I'm going to explain something later with the muscles it can do glycogenolysis but to a

certain point okay so we know that this is occurring in the liver we know it's occurring in the muscles but it stops at a certain point in the muscles and we'll discuss that now the next question is why is it occurring so the next question to ask ask is why is this reaction occurring it's occurring because the blood glucose levels are low so now it's the opposite of glyco Genesis now the blood glucose levels are low so low blood glucose what do you call that whenever your blood glucose level is low they call this hypo

glycemia so normally like I said before the normal range of blood glucose levels is about you know if you give it a range 70 to 130 milligrams for DL anything significantly below that point is actually going to cause this glycogenolysis process to occur why is it going to occur because if you're breaking out glycogen into glucose and you can get that glucose into the blood you can contribute to the blood glucose levels to bring it back up now when would this uh blood glucose levels be dropping it would be dropping when you in What's called

the fasting State you know the fasting state is also Al called the PO postabsorptive state so you haven't eaten in a while if you haven't eaten in a while your blood glucose levels are going to drop a little bit so what hormones are going to be kicked into action is specifically going to be glucagon um you're also going to have epinephrine you'll have norepinephrine and you can even have certain other types of hormones maybe even growth hormone or thyroid hormone but the main ones that we're going to be talking about is going to be primarily

glucagon and epinephrine and norepinephrine these are the ones we'll talk more about but again there is other enzymes that you should know so we got where it's occurring liver in the muscles we know why it's occurring it's because the blood glucose levels is low we have hypoglycemia and we could be in the fasting state or we could be in the star we could be starving ourselves we're not eating food right and the main hormones that are going to be involved in this process is going to be glucagon epinephrine norepinephrine and even growth hormone and other

hormones now we have to go over how this process is occurring and that's what we're going to discuss here so now we have to get into how is this process occurring okay so if you guys remember we left off with this glycogen polymer okay and what was this base molecule that was holding this up this base molecule was called glyco jenin that was that protein molecule right that was holding on to this entire glycogen polymer now we're going to need a special enzyme in this process this enzyme is a really cool enzyme look at this

guy let's say here I have this enzyme I have this enzyme here and he's going to cut specific bonds what are the specific bonds that this enzyme is going to cut the specific bonds he's going to cut is going to be the alpha 14 glycidic bonds so if you guys remember where is those Alpha 14 glycosidic bonds remember at the head of the glucose molecule that's the one carbon at the bottom part is the four carbon and this over here is the six carbon so again what is this one right here this is the one

carbon this is back here this is the four carbon right there and this is the six carbon right the bond here between this guy this is a 14 Alpha 14 glycidic bond this is a alpha4 glycidic bond alpha1 14 alpha4 alpha1 14 you guys get the point so all of these bonds right here if I were to highlight it that is a alpha 14 again this is a alpha1 14 Alpha 14 this enzy time is going to come over and he's got something really interesting in his he's carrying a satchel so look at this Satchel

okay he's got this Satchel wrapping over you know what he's got in this Satchel that he's carrying he's got a lot of phosphates so let's say that I draw in here the phosphates and I'm going to put the phosphates as this pink structure so here's our phosphates so I have a whole bunch of phosphates in this Satchel this enzyme is called glycogen phosphor what is this enzyme going to do in one hand he's going to grab onto a phosphate group the other hand he's going to hold on to this glycogen molecule and then he's going

to take that phosphate and he's going to fling it at that actual glycogen molecule when he flings that actual phosphate at the glycogen molecule he's specifically flinging it in between the this what is this Bond here again guys here I'll actually zoom in on this Bond here so let me make that Bond right there just for this sake of this and again here's your glucose molecule this is the 1 end 4 end and 6 end he's taking that phosphate he dips into his you know Satchel here's his phosphates he's going to take this phosphate and

he's going to throw that phosphate into this Bond What bond this Alpha 14 glycidic Bond when he does that it breaks the bond so now this bond is actually going to break when it breaks it adds the phosphate onto the one carbon what is this molecule going to be as it leaves so as this molecule is leaving what are we going to have here we're going to have glucose so here's our glucose and again this is the six carbon and then what carbon is that phosphate going to be on that phosphate is on the number

one carbon so again if you guys remember this is one carbon right here this is the sixth carbon and this is the fourth carbon right there we just put that glucose on the one carbon right there so now we call this this phosphate is on that one carbon of glucose they call this glucose one phosphate so again this molecule here is called glucose one phosphate who formed him glycogen phosphor you know he's going to do this with each and every single one of these guys he's going to keep going through these guys like he's eating

Fig Newtons he's just drilling through those p puppies as he drills through those puppies he keeps adding what phosphates so let's say here I show you that guy right there this is coming from a phosphate I add a phosphate into these next carbon I add a phosphate into that one I add a phosphate into this one and then let me show you something here real quick this glycogen phosphor is restricted at a certain point so let's say I get to a certain point he can you see this Bond right here what is this green Bond

here called we really need to understand what that GRE bond is well it's coming off of the six carbon of this glucose and linking to the one carbon of this glucose so what do you call this Bond guys Alpha six glyco cdic Bond if I count one two three four this guy right here I'm going to put a mark right here right there one two three I'm sorry whoops let me come back here put this glucose back on here fix that guy up if I count from this point from the alpha six gly ayic Bond

one two three four at that point right there this is where he can no longer go past so this glycogen phosphor can no longer go past that point so one two three four carbons so four glucose molecules away from this alpha 1 six glycidic Bond he cannot pass so he can add a phosphate into that Bond right there but then he stops right there but again if you guys remember as he's adding phosphates into these alpha 1 14 glycidic bonds through 1 2 3 4 five molecules how many of these glucose one phosphates would I

form from that process I would form at least five so far five glucose one phosphates okay but then so let's erase that now so we get to this point here so now he he added phosphates into each one of these right so all these phosphates as they're added into each one of these we get to this point here we stop at this glucose model Ule why because he is restricted at this point whenever glycogen phosphorus gets to this last point to where there is four glucose molecules away from the alpha4 glycidic bond he stops he

can no longer perform his function now there's going to be another enzyme that will come into play look at this enzyme let's look at this guy here's this guy this enzyme here is a cute little enzyme and what he's going to do is is he's going to come over here and he's going to take his hand and you see this right here this is the alpha one6 glycidic Bond that's bound to this carbon that one carbon to that glucose but in between these two glucose molecules is an alpha 14 he cuts this Bond right there

so he goes to the alpha6 doesn't touch that yet he comes right over here to this Alpha 14 between this glucose that's bound with this alpha6 gly ayic Bond and the glucose right after after it and cuts that Bond so he cuts that Bond right there and you know what he's going to do he's going to do something very very very cool he's going to take this one two three glucose molecules and transfer it onto this guy that's what he's going he's going to take these three glucose molecules and he's going to transfer it onto

this guy so what did he do first thing he did is he sliced that Bond right there he sliced that thing up then he took these three glucose molecules with his other hand and transfers them there okay now what is it going to look like I should have three glucose molecules coming up here one two three and again six carbon six carbon there and again give them the smiley faces so we know orientation right so now what's going to be left over here let's draw what's left over after we've done that after we've transferred you're

going to have this one glucose molecule left over this one glucose molecule is left over this enzyme look what his foot does so again he used this portion here to transfer this portion here to cut and now look what he's going to do with this portion he's got toenails that are like ruffled potato chips and look at this he's going to Cut That B right there if he cuts this alpha6 glyc ayic Bond he's going to release away what what is this this is glucose does he have a phosphate on him though no so what

is this molecule here called look what's going to come out of this this is coming from this guy what is this molecule here that we released one glucose molecule I release out of this one free glucose molecule so if you can imagine here for every five of these glucose one phosphates I produced only one of these glucose that's obviously you know not a completely correct concept here but you get the point that I'm producing significantly large amounts of glucose 1 phosphates and very very little amounts of fre glucose so again let's get this straight one

more time what is the name of this component of this enzyme this component of this enzyme is breaking that alpha6 glycidic Bond so it has alpha6 gluco pidas activity then what was this hand doing this hand was cutting the alpha 14 glycidic Bond so he has Alpha 14 gluco sidas activity and then what was this other hand doing it was transferring so we're just going to put that it was transferring those other three glucose molecules onto the other elongating chain so then what does he do he has this three glucose transfer okay what is the

name of this enzyme well if you think about it these were branches right what did he basically do he kind of helped to get and debranch that part off so if he's debranching it wouldn't this just be called the debranching enzyme Yep this enzyme here is called the D branching enzyme so now if you can imagine now these guys are just going to continue to keep doing this so he's going to release off that free glucose that free glucose is going to be gone so let's get rid of this alpha6 glycidic bond is now gone

he broke that sucker what is this I'm going to do he's going to see a whole bunch of these guys well let me count this is an alpha one six guys so one two three four I cannot go past this point he says so what does he do reaches into a satchel pulls out phosphates and starts adding phosphates at what point does he add the phosphates right here right here right here right there right there right there right there and again right here if he does that what am I going to get out of all

of these puppies here I'm going to get out of all of these glucose one phosphate and then what's going to happen as a result all of these are going to be broken down so I've broken down all of these guys as I break down all of these guys what's left 1 2 3 4 hm this is an alpha one six gly ayic Bond right here right this is a alpha one six glycosidic Bond what enzyme comes into play ah the debranching enzyme he comes over here what does he do he has this one alpha 14

glucosidase activity and he cuts this Bond then what he to do he has a three glucose transferring part so then he takes this guy and what does he do he can add it on to this one so then he takes these three glucose molecules and adds them on so one two three and again here's my six carbon six carbon six carbon so then what happens These Guys these are all gone after these are all gone what am I left with I'm left with this one little lome Lonesome glucose molecule what happens with this guy well

then he has this Alpha One six glucosidase part so what does he do he cuts this Bond as a result of cutting this Bond what do I release free glucose and you guys can now get the point of what's actually happening here there's going to be a constant interplay between this debranching enzyme who's doing what cutting the alpha one4 glycidic Bond right that is actually going to be at that glucose point right here right and it has to be how many glucose molecules away from the alpha 1 16 1 2 3 4 so what does

he do what does the debranching enzyme do he cuts the alpha4 gly ayic bond right there from the glucose who's connected with the alpha 1 16 and Alpha 14 he cuts that Bond then what does he do he transfers those three groups of glucose onto a longer chain what else does he do he has a alpha6 glucosidase activity so you can cut that Bond and release free glucose then what is the glycogen phosphor l doing all he's doing is he's reaching into a satal which is rich in phosphates and transferring those phosphates onto the one

carbon of the glucose in this polymer and forming glucose one phosphate also you know what else this enzyme has that's really special you he's got ears and from his ears he has this little earrings which are made up of paradoxal phosphate so here's his paradoxal phosphate earrings these are important because paradoxal phosphate is actually a component of this transfer the transfer of these phosphates onto these glucose molecules to form glucose one phosphate so he's extremely important and paradoxal phosphate is actually a derivative of vitamin B6 okay so now we've done this process we know exactly

how glycogen is broken down because we could keep going through this but it all should make sense by this point now we have to go to this point what happens to these guys well you know that free glucose it's not chained down by any phosphat so where could he go he could go right out of the cell and go where let's say over here outside of this liver cell there is a blood vessel if there's a blood vessel right here what's going to happen it's going to go right into the blood when it goes right

into the bloodstream what's it going to do to the actual glucose levels in the blood it's going to increase the blood glucose levels if it increases the blood glucose levels what's going to happen then we fixed the problem what was the problem the the problem was that we had low blood glucose levels and we fixed it so now what is going to be here in the blood this free glucose molecule okay there's our glucose but it's only one glucose right out of out of many many of those glucose one phosphates we're forming very little free

glucose so really insignificant amounts of this glucose is really being contributed to the blood glucose levels this guy is the one who's accounting for significant amounts of the blood glucose levels because we're making tons of him okay so what's happening to him okay so let's say I take this glucose 1 phosphate molecule you remember that enzyme guys there was that special enzyme he was taking the glucose one phosphate and he was shifting that phosphate from the one carbon to the six carbon what was that enzyme guys that enzyme that was stimulating this step was called

phospho gluco mutase this enzyme is extremely special because it's reversible remember how this enzyme is also acting in the reversible Direction converting glucose 6 phosphate into glucose 1 phosphate so this is a reversible enzyme what's going to be the result if I transfer the phosph from the one carbon to the sixth carbon I get glucose six phosphate so now I'm going to have again what am I going to have over here I'm going to have that phosphate now on the six carbon so let's show that over here I'm going to have my phosphate and again

just to get our carbon straight guys this is one carbon six carbon four carbon this molecule is now called glucose 6 phosphate here's where we run into an issue glucose 6 phosphate can it be transported out through this actual glut transporter no okay so the liver and the kidneys and certain types of parts of the GI tract specifically the dadum have a special type of enzyme only exclusive to them in other words this enzyme this enzy enzy here is extremely special this enzyme is called glucose six phosa Tas now I am going to be very

very picky with this because it's important this glucose 6 phosphotase is only found in specific organs the liver the kidneys specifically in the proximal convoluted tubal and parts of the GI tract particularly the dadum this enzyme is not in the muscles so if you do not have this enzyme in the muscles can the muscle contribute to the blood glucose levels no we will explain that in the part of gluconeogenesis via the glucose alanine cycle and the Corey cycle how the muscle is actually getting the glucose into the blood it's indirectly okay for right now we're

only going to focus on the glucose 6 phosphate getting into the blood in the liver so now let's take this glucose 6 phosphate and see what it's doing over here okay so what is this guy right here this is our specifically our glucose six phosphate and how do I know that again because this is the one carbon four carbon six carbon this glucose 6 phosphate is going to get brought into this what is this structure here you know this structure is actually called the endoplasmic reticulum so this is the endoplasmic reticulum particularly the smooth are

what happens is this glucose 6 phosphate gets brought in through a glut transporter and we particularly call this blood transporter on the outside that brings the glucose in we call it T1 so now this glucose 6 phosphate is going to be brought into the ER when it's brought into the endoplasmic reticulum it's acted on by a glucose 6 phosphatase so then look this guy is going to react with the glucose 6 phosphatase enzyme what is that glucose 6 phosphatase enzyme going to do it's going to rip out a phosphate so that phosphate is actually going

to be lost what is this new molecule now this new molecule that we formed here is now going to be just free glucose and where's that free glucose going to go you know there's another transporter that transports the glucose out it's another glut transporter but we specifically call it T2 this guy is going to transport this free glucose out of the endoplasmic reticulum and back out into the cytoplasm and so now I'm going to have my free glucose molecule here where is this free glucose molecule going to go now now it can go out through

the Transporters so it can go out through the Transporters and then where out into the blood and if it gets put onto the bloodstream and we're having a lot of this activity occurring what's going to happen to our blood glucose levels eventually it's going to come back up So eventually we're going to bring the blood glucose levels back up and try to be able to bring it back to the homeostatic range now again this activity of taking the glucose 6 phosphatase and acting on glucose 6 phosphate to make glucose can only occur in the liver

the kidneys and in the git but primarily if you think about it we didn't mention glycogenolysis occurring within the kidneys or the git so we're mainly only going to be focusing on this activity that you just witnessed only in the liver okay so now the reason why I'm telling you that is because this enzyme is again not in the muscles the muscles can do glycogen alysis but they do not have this enzyme so they cannot release free glucose into the blood they get stuck at glucose 6 phosphate so this is where it gets stuck in

the muscles let's actually put that it's stuck in this confirmation stuck like this in muscles there's another way to get that glucose into free glucose but it's an indirect mechanism and we're going to talk about it it's two cycles that we'll discuss and we're going to talk talk about the Corey cycle and the glucose alanine cycle we'll talk about this whenever we go over gluconeogenesis regulation okay all right guys so in this video we covered a lot about the glycogenolysis processes in the next video we're going to go over a brief concept of the actual

regulation of this actual process and different types of clinical correlations that can come whenever certain of these enzymes are mutated all right Engineers I hope all this made sense I hope you guys enjoyed it until next time