Metabolism | Glycogenolysis

I ninja nerds in this video we're going to talk about glycogen Alice's because haven't already seen it go watch our video and glycogenesis kids we're going to really be depending upon that concept first okay so if you guys watch like the genesis you know that we basically synthesize the glycogen by the activity of the glycogen synthase and the branching enzyme right well we're going to do now is we're going to show you exactly how does a glycogen polymer is getting broken back down into glucose but before we do that we have to understand what is this process call whenever we're breaking down the glycogen back into glucose it's called glycogenolysis license 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 out where in the liver and in the muscles however it can occur in other tissues too but we're focusing on this 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 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 you call that whenever your blood glucose level is low they call this hypo glycaemia 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 throw it cause this glycogen alysus profits to occur why is it going to occur because if you're breaking down 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 blood glucose levels be dropping it would be dropping when you're in what's called the fasting state you know the fasting state is also called the poor's post-absorptive 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 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 a 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 start we could be starving ourselves we're not eating food right and the main hormones that are gonna be involved in this process is going to be glucagon epinephrine norepinephrine and even growth hormone 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 luggage and 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 1-4 glycosidic bonds so if you guys remember where is those alpha 1-4 glycosidic bonds remember 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 one for alpha one four glycosidic bond this is a alpha one four glycosidic bond alpha one four off one for off one for you guys get the point so all of these bonds right here if I were to highlight it that is a alpha one four again this is a alpha one four alpha one four this enzyme is going to come over and he's got something really interesting in this he's carrying a satchel so look at this satchel okay he's got this satchel wrapping over him you know buddy's got in this satchel that he's caring he's got a lot of phosphates so let's say that I draw in here the phosphate and I'm going to put the phosphates as this pink structure so here's our philosophies so I have a whole bunch of phosphates in this satchel this enzyme is called glycogen phosphorylase what did this enzyme going to do in one hand he's going to grab on to a phosphate group the other hand is going to hold onto 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 this what is this bond here getting 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 one end for end and six end he's taking that phosphate he dips into its you know satchel here's his phosphate he's going to take this phosphate and he's going to throw that phosphate into this bond what bond this alpha 1-4 glycosidic 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 me number one carbon so again if you guys remember this is one carbon right here this is the six 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 1-phosphate so again this molecule here is called glucose 1-phosphate who formed him glycogen phosphorylase you know he's going to do this with each and every single one of these guys is gonna keep going through these guys like he's eating Fig Newtons hanging you just drill him through those 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 philosophy I add a phosphate into these next carbon I add a phosphate into that one add a phosphate into this one and then let me show you something real quick this glycogen phosphorylase 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 green bond is what's coming off of the six carbon of this glucose and linking to the 1 carbon of this glucose so what do you call this bond guys alpha one six glyco siddik 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 they come back here put this glucose back on here fix that guy up if I count from this point from the alpha one six like to study bond one two three four at that point right there this is where he can no longer go past so this glycogen phosphorylase can no longer go past that point so one two three four carbons so for glucose molecules away from this alpha 1-6 glycosidic bond he cannot pass so he can't 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 1-4 glycosidic bonds through 1 2 3 4 5 molecules how many of these glucose 1-phosphate swear i have formed from that process I would form at least five so far 5 glucose 1-phosphate ok but then so let's erase that now so we get to this point here so now he added Fawcett's 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 stopped at this glucose molecule why because he is restricted at this point whenever glycogen phosphorylase gets to this last point to where there's four glucose molecules away from the alpha 1-4 glycosidic 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 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 for 1-6 glycosidic bond that's bound to this carbon that one carbon like glucose but in between these two glucose molecules is an alpha 1-4 he cuts this bond right there so he goes to the alpha one six doesn't touch that yet he comes right over here to this alpha 1-4 between this glucose that's bound with this alpha 1-6 glycosidic bond and the glucose right after it and cut that bond so he cuts that bond right there and you know what he's going to do he could do something very very very cool he's going to take this 1 2 3 glucose molecules and transfer it onto this guy doesn't he's gonna 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 are they gonna look like I should have three glucose molecules coming up here 1 2 3 and again 6 carbon 6 carbon there and again give them the smiley faces so we know orientation like 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 is flipped us so again you use 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 ball right there if he cuts this alpha 1-6 glycosidic 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 Molitor here called look it'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 1-phosphate I produce only one of these glucose that's obviously you know not a complete the correct concept here but you get the point that I'm producing significantly large amounts of glucose 1-phosphate and very very little amounts of free 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 alpha 1-6 glycosidic bond so it has alpha one six gluco side ace activity then almost this hand doing this hand was cutting the alpha 1-4 glycosidic bond so he has alpha 1-4 gluco side ace activity and then what was this other hand doing it was transferring so we're just going to put that it was transferring those all there three glucose molecules onto the other along gating chain so then what did you do he has this free 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 be branch that part off so he's D branching 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 let's get rid of this alpha 1-6 glycosidic bond is now gone he broke that sucker what is this enzyme 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 mmm I cannot go past this point he says so what did you do reaches into a satchel pulls out phosphate and starts adding phosphates at what point does he add the phosphate 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 all of these puppies here I'm going to get out of all of these glucose-1-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 one two three four hmm this is an alpha 1-6 glycosidic bond right here all right this is a alpha 1-6 glycosidic bond one enzyme comes into play ah the debranching enzyme he comes over here what does he do he has this one alpha 1-4 glucose is activity and he cuts this bond then what did you do he has a three glucose transferring part so then he takes this guy and wanted to 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 low some lonesome glucose molecule what happens with this guy well then he has this alpha one six glucose I taste part so what did 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 de branching enzyme who's doing what cutting the alpha 1-4 glycosidic 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 one six one two three four so what does he do what if the debranching enzyme do he cuts the alpha 1-4 glycosidic bond right there from the glucose who's connected with the alpha one six and alpha 1-4 he cuts that bond then what is he transfers those three groups of glucose onto a longer chain what else does he do he has a alpha one six glucose I taste activity so he can cut that bond and release free glucose then what does the glycogen phosphorylase doing all he's doing is he's reaching into a satchel which is rich in phosphates and transferring those phosphates onto the one carbon of the glucose and this polymer and forming glucose 1-phosphate also you know what else this enzyme has that's really special you've got years and from his ears he has these little earrings which are made up of pyridoxal phosphate so here's his paradoxical phosphate earrings these are important because pyridoxal phosphate is actually a component of this transfer the transfer of these phosphates onto these glucose molecules to form glucose 1-phosphate so he's extremely important and pyridoxal 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 phosphates where could he go can you 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 in we fix the problem what was the problem the problem was that we had to 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 1-phosphate so we're forming very little free glucose so really insignificant amount of this glucose is really being contributed to the blood glucose levels this guy's the one whose accounting for significant amounts of the blood glucose level 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 remember that enzyme guys there were that special enzyme he was taking the glucose 1-phosphate and he was shifting that faucet 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 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 faucet from the one carbon to the six carbon I get glucose 6-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 carbons let's show that over here I'm going to have my phosphate and again just to get a 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 now okay so the liver and the kidneys and certain types of parts of the GI tract specifically the duodenum have a special type of enzyme only exclusive to them in other words this enzyme this enzyme here is extremely special this enzyme is called glucose-6-phosphatase now I'm going to be very very picky with this because it's important this glucose 6-phosphate is only found in specific organs the liver the kidneys specifically in the proximal convoluted tubule and parts of the GI tract particularly the duodenum this enzyme is not on 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 if you have the glucose alanine cycle in the Cori 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 6-phosphate and how do I know that again because this is the carbon four carbon six carbon this glucose 6-phosphate is going to get brought into this what is this structure here another structure is actually called the endoplasmic reticulum so this is the endoplasmic reticulum particularly the smooth ER what happens is this glucose 6-phosphate gets brought in through a glut transporter and we particularly call this glut 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-phosphate agent I'm going to do it's going to rip out a phosphate so that philosophy 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 is 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 I can go out through the transporters and then we're out into the blood and if it gets put onto the blood stream 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 GI t but primarily if you think about it we didn't mention glycogenolysis occurring within the kidneys of the GI T so we're mainly only going to be focusing on this activity that you just witnessed only deliver 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 alysus 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 conformation 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 about the Cori 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 glycogen alysus 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 iron engines I hope all this made sense I hope you guys enjoyed it until next time

Channel: Ninja Nerd

Views: 267,728

Keywords: glycogenolysis, metabolism

Id: YQV_ODVCzQQ

Length: 24min 32sec (1472 seconds)

Published: Wed May 31 2017