0:08 I engineers in this video we're going to
0:10 talk about glycogen alysis if you guys
0:12 haven't already seen it go watch our
0:13 video on glycogenesis because we're
0:15 going to really be depending upon that concept
0:16 concept
0:18 first okay so if you guys watch
0:19 glycogenesis you know that we basically
0:21 synthesize glycogen by the activity of
0:23 the glycogen synthes and the branching
0:25 enzyme right what we're going to do now
0:26 is we're going to show you exactly how
0:29 this glycogen polymer is getting broken
0:32 back down into gluc ose but before we do
0:33 that we have to understand what is this
0:35 process called whenever we're breaking
0:37 down the glycogen back into glucose it's
0:40 called glycogenolysis Lis meaning cut
0:42 glycogen right so we're cutting the
0:45 glycogen and forming glucose now once
0:48 again where is this process occurring
0:50 where is this glycogenolysis process
0:53 occurring it's specifically occurring
1:01 liver and in the
1:04 muscles however it can occur in other
1:05 tissues too but we're focusing on the
1:07 more significant ones where this is
1:08 occurring okay so it's occurring where
1:11 in the liver and in the muscles but I'm
1:13 going to explain something later with
1:16 the muscles it can do glycogenolysis but
1:19 to a certain point okay so we know that
1:20 this is occurring in the liver we know
1:22 it's occurring in the muscles but it
1:23 stops at a certain point in the muscles
1:26 and we'll discuss that now the next
1:29 question is why is it occurring so the
1:31 next question to ask ask is why is this
1:34 reaction occurring it's occurring
1:38 because the blood glucose levels are low
1:40 so now it's the opposite of glyco
1:42 Genesis now the blood glucose levels are
1:44 low so low blood glucose what do you
1:46 call that whenever your blood glucose
1:50 level is low they call this hypo
1:52 hypo
1:54 glycemia so normally like I said before
1:56 the normal range of blood glucose levels
1:58 is about you know if you give it a range
2:01 70 to 130 milligrams for DL anything
2:03 significantly below that point is
2:04 actually going to cause this
2:07 glycogenolysis process to occur why is
2:09 it going to occur because if you're
2:10 breaking out glycogen into glucose and
2:12 you can get that glucose into the blood
2:14 you can contribute to the blood glucose
2:18 levels to bring it back up now when
2:20 would this uh blood glucose levels be
2:23 dropping it would be dropping when you
2:26 in What's called the
2:29 fasting State you know the fasting state
2:31 is also Al called the PO postabsorptive
2:33 state so you haven't eaten in a while if
2:34 you haven't eaten in a while your blood
2:35 glucose levels are going to drop a
2:37 little bit so what hormones are going to
2:40 be kicked into action is specifically
2:43 going to be
2:46 glucagon um you're also going to have
2:48 epinephrine you'll have
2:50 norepinephrine and you can even have
2:51 certain other types of hormones maybe
2:53 even growth hormone or thyroid hormone
2:54 but the main ones that we're going to be
2:57 talking about is going to be primarily
2:59 glucagon and epinephrine and
3:00 norepinephrine these are the ones we'll
3:02 talk more about but again there is other
3:05 enzymes that you should know so we got
3:06 where it's occurring liver in the
3:07 muscles we know why it's occurring it's
3:09 because the blood glucose levels is low
3:11 we have hypoglycemia and we could be in
3:13 the fasting state or we could be in the
3:14 star we could be starving ourselves
3:16 we're not eating food right and the main
3:17 hormones that are going to be involved
3:19 in this process is going to be glucagon
3:20 epinephrine norepinephrine and even
3:24 growth hormone and other hormones now we
3:26 have to go over how this process is
3:27 occurring and that's what we're going to
3:29 discuss here so now we have to get into how
3:31 how
3:34 is this process occurring okay so if you
3:35 guys remember we left off with this
3:38 glycogen polymer okay and what was this
3:40 base molecule that was holding this up
3:43 this base molecule was called glyco
3:45 glyco
3:47 jenin that was that protein molecule
3:50 right that was holding on to this entire
3:52 glycogen polymer
3:54 now we're going to need a special enzyme
3:56 in this process this enzyme is a really
3:59 cool enzyme look at this guy let's say
4:03 here I have this enzyme I have this
4:06 enzyme here and he's going to cut
4:10 specific bonds what are the specific
4:12 bonds that this enzyme is going to cut
4:14 the specific bonds he's going to cut is
4:17 going to be the alpha 14
4:21 glycidic bonds so if you guys remember
4:24 where is those Alpha 14 glycosidic
4:27 bonds remember at the head of the
4:29 glucose molecule that's the one carbon
4:31 at the bottom part is the four carbon
4:32 and this over here is the six carbon so
4:33 again what is this one right here this
4:36 is the one carbon this is back here this
4:38 is the four carbon right there and this
4:41 is the six carbon right the bond here
4:44 between this guy this is a 14 Alpha 14
4:47 glycidic bond this is a alpha4 glycidic
4:49 bond alpha1 14 alpha4 alpha1 14 you guys
4:52 get the point so all of these bonds
4:53 right here if I were to highlight it
4:56 that is a alpha 14 again this is a
4:58 alpha1 14 Alpha
5:01 14 this enzy time is going to come over
5:02 and he's got something really
5:04 interesting in his he's carrying a
5:06 satchel so look at this
5:08 Satchel okay he's got this Satchel wrapping
5:10 wrapping
5:12 over you know what he's got in this
5:13 Satchel that he's
5:17 carrying he's got a lot of phosphates so
5:18 let's say that I draw in here the
5:20 phosphates and I'm going to put the
5:22 phosphates as this pink structure so
5:24 here's our phosphates so I have a whole
5:26 bunch of phosphates in this
5:43 phosphor what is this enzyme going to do
5:45 in one hand he's going to grab onto a
5:47 phosphate group the other hand he's
5:48 going to hold on to this glycogen
5:49 molecule and then he's going to take
5:51 that phosphate and he's going to fling
5:53 it at that actual glycogen molecule when
5:55 he flings that actual phosphate at the
5:58 glycogen molecule he's specifically
6:00 flinging it in between the this what is
6:01 this Bond here again guys here I'll
6:03 actually zoom in on this Bond here so
6:05 let me make that Bond right there just
6:07 for this sake of this and again here's
6:10 your glucose molecule this is the 1 end
6:15 4 end and 6 end he's taking that
6:17 phosphate he dips into his you know
6:20 Satchel here's his phosphates he's going
6:21 to take this phosphate and he's going to
6:24 throw that phosphate into this Bond What
6:28 bond this Alpha 14 glycidic Bond when he
6:30 does that it breaks the bond so now this
6:33 bond is actually going to break when it
6:35 breaks it adds the phosphate onto the
6:37 one carbon what is this molecule going
6:40 to be as it leaves so as this molecule
6:41 is leaving what are we going to have
6:44 here we're going to have
6:47 glucose so here's our glucose and again
6:50 this is the six carbon and then what
6:52 carbon is that phosphate going to be on
6:54 that phosphate is on the number one
6:57 carbon so again if you guys remember
6:59 this is one carbon right here this is
7:01 the sixth carbon and this is the fourth
7:03 carbon right there we just put that
7:06 glucose on the one carbon right there so
7:08 now we call this this phosphate is on
7:10 that one carbon of glucose they call this
7:12 this
7:16 glucose one phosphate so again this
7:18 molecule here is called glucose one
7:20 phosphate who formed him glycogen
7:22 phosphor you know he's going to do this
7:23 with each and every single one of these
7:25 guys he's going to keep going through
7:28 these guys like he's eating Fig Newtons
7:29 he's just drilling through those p
7:31 puppies as he drills through those
7:34 puppies he keeps adding what phosphates
7:37 so let's say here I show you that guy
7:39 right there this is coming from a
7:41 phosphate I add a phosphate into these
7:44 next carbon I add a phosphate into that
7:47 one I add a phosphate into this one and
7:49 then let me show you something here real
7:51 quick this glycogen phosphor is
7:54 restricted at a certain point so let's
7:55 say I get to a certain point he can you
7:57 see this Bond right here what is this
7:58 green Bond here called we really need to
8:00 understand what that GRE bond is well
8:02 it's coming off of the six carbon of
8:03 this glucose and linking to the one
8:05 carbon of this glucose so what do you
8:10 call this Bond guys Alpha six glyco
8:12 glyco cdic
8:14 cdic
8:20 Bond if I count one two three four this
8:22 guy right here I'm going to put a mark right
8:23 right
8:27 here right there one two three I'm sorry
8:31 whoops let me come back here
8:33 put this glucose back on here fix that
8:35 guy up if I count from this point from
8:37 the alpha six gly ayic Bond one two
8:40 three four at that point right there
8:44 this is where he can no longer go past
8:46 so this glycogen phosphor can no longer
8:49 go past that point so one two three four
8:51 carbons so four glucose molecules away
8:53 from this alpha 1 six glycidic Bond he
8:56 cannot pass so he can add a phosphate
8:58 into that Bond right there but then he
9:00 stops right there but again if you guys
9:03 remember as he's adding phosphates into
9:05 these alpha 1 14 glycidic bonds through
9:08 1 2 3 4 five molecules how many of these
9:10 glucose one phosphates would I form from
9:13 that process I would form at least five
9:17 so far five glucose one phosphates okay
9:19 but then so let's erase that now so we
9:20 get to this point here so now he he
9:22 added phosphates into each one of these
9:24 right so all these phosphates as they're
9:26 added into each one of these we get to
9:29 this point here we stop at this glucose
9:30 model Ule why
9:32 why
9:35 because he is restricted at this point
9:37 whenever glycogen phosphorus gets to
9:38 this last point to where there is four
9:41 glucose molecules away from the alpha4
9:43 glycidic bond he stops he can no longer
9:45 perform his function now there's going
9:47 to be another enzyme that will come into
9:50 play look at this enzyme let's look at
9:53 this guy here's this
9:57 guy this enzyme here is a cute little
10:00 enzyme and what he's going to do is is
10:03 he's going to come over here and he's
10:06 going to take his hand and you see this
10:07 right here this is the alpha one6
10:09 glycidic Bond that's bound to this
10:12 carbon that one carbon to that glucose
10:13 but in between these two glucose
10:15 molecules is an alpha
10:19 14 he cuts this Bond right there so he
10:21 goes to the alpha6 doesn't touch that
10:23 yet he comes right over here to this
10:25 Alpha 14 between this glucose that's
10:28 bound with this alpha6 gly ayic Bond and
10:30 the glucose right after after it and
10:33 cuts that Bond so he cuts that Bond
10:33 right there and you know what he's going
10:35 to do he's going to do something very
10:38 very very cool he's going to take this
10:40 one two three glucose molecules and
10:43 transfer it onto this guy that's what
10:44 he's going he's going to take these
10:45 three glucose molecules and he's going
10:47 to transfer it onto this guy so what did
10:49 he do first thing he did is he sliced
10:51 that Bond right there he sliced that thing
10:52 thing
10:55 up then he took these three glucose
10:57 molecules with his other
11:00 hand and transfers them there
11:02 okay now what is it going to look like I
11:03 should have three glucose molecules
11:06 coming up here one two three and again six
11:07 six
11:10 carbon six carbon there and again give
11:11 them the smiley faces so we know orientation
11:12 orientation
11:14 right so now what's going to be left
11:18 over here let's draw what's left over
11:20 after we've done that after we've
11:22 transferred you're going to have this
11:25 one glucose molecule left over this one
11:27 glucose molecule is left
11:30 over this enzyme look what his foot does
11:32 so again he used this portion here to
11:35 transfer this portion here to cut and
11:37 now look what he's going to do with this
11:40 portion he's got toenails that are like
11:43 ruffled potato chips and look at this
11:45 he's going to Cut That B right there if
11:48 he cuts this alpha6 glyc ayic Bond he's
11:51 going to release away what what is this
11:52 this is glucose does he have a phosphate
11:55 on him though no so what is this
11:56 molecule here called look what's going
11:57 to come out of
12:00 this this is coming from this guy what
12:02 is this molecule here that we
12:07 released one glucose molecule I release
12:10 out of this one free glucose molecule so
12:13 if you can imagine here for
12:16 every five of these glucose one
12:17 phosphates I produced only one of these
12:20 glucose that's obviously you know not a
12:22 completely correct concept here but you
12:24 get the point that I'm producing
12:26 significantly large amounts of glucose 1
12:28 phosphates and very very little amounts
12:31 of fre glucose so again let's get this
12:33 straight one more
12:36 time what is the name of this component
12:38 of this enzyme this component of this
12:41 enzyme is breaking that alpha6 glycidic
12:43 Bond so it has alpha6
12:45 alpha6
12:47 gluco pidas
12:51 activity then what was this hand doing
12:55 this hand was cutting the alpha 14
13:00 glycidic Bond so he has Alpha 14
13:04 gluco sidas activity and then what was
13:06 this other hand doing it was
13:08 transferring so we're just going to put
13:10 that it was transferring those other
13:15 three glucose molecules onto the other
13:17 elongating chain so then what does he do
13:20 he has this three glucose
13:22 glucose transfer
13:24 transfer
13:27 okay what is the name of this enzyme
13:29 well if you think about it these were
13:31 branches right what did he basically do
13:33 he kind of helped to get and debranch
13:35 that part off so if he's debranching it
13:36 wouldn't this just be called the
13:38 debranching enzyme
13:41 Yep this enzyme here is called the D
13:44 D
13:48 branching enzyme so now if you can
13:50 imagine now these guys are just going to
13:52 continue to keep doing this so he's
13:54 going to release off that free glucose
13:55 that free glucose is going to be gone so
13:57 let's get rid of this alpha6 glycidic
14:01 bond is now gone he broke that sucker
14:02 what is this I'm going to do he's going
14:04 to see a whole bunch of these guys well
14:06 let me count this is an alpha one six
14:10 guys so one two three four I cannot go
14:12 past this point he says so what does he
14:15 do reaches into a satchel pulls out
14:17 phosphates and starts adding phosphates
14:19 at what point does he add the phosphates
14:22 right here right here right here right
14:23 there right there right there right
14:26 there and again right
14:28 here if he does that what am I going to
14:30 get out of all of these puppies here I'm
14:32 going to get out of all of
14:36 these glucose one phosphate and then
14:37 what's going to happen as a result all
14:40 of these are going to be broken down so
14:42 I've broken down all of these guys as I
14:45 break down all of these guys what's left
14:49 1 2 3 4 hm this is an alpha one six gly
14:51 ayic Bond right here right this is a
14:53 alpha one six glycosidic Bond what
14:55 enzyme comes into play ah the
14:57 debranching enzyme he comes over here
15:00 what does he do he has this one alpha 14
15:02 glucosidase activity and he cuts this
15:05 Bond then what he to do he has a three
15:07 glucose transferring part so then he
15:09 takes this guy and what does he do he
15:11 can add it on to this one so then he
15:14 takes these three glucose molecules and
15:19 adds them on so one two three and again
15:21 here's my six carbon six carbon six
15:23 carbon so then what happens These Guys
15:26 these are all gone after these are all
15:28 gone what am I left with I'm left with
15:30 this one little lome Lonesome glucose
15:33 molecule what happens with this guy well
15:35 then he has this Alpha One six
15:38 glucosidase part so what does he do he
15:40 cuts this Bond as a result of cutting
15:43 this Bond what do I release free glucose
15:45 and you guys can now get the point of
15:47 what's actually happening here there's
15:49 going to be a constant interplay between
15:52 this debranching enzyme who's doing what
15:54 cutting the alpha one4 glycidic Bond
15:56 right that is actually going to be at
15:59 that glucose point right here right and
16:00 it has to be how many glucose molecules
16:04 away from the alpha 1 16 1 2 3 4 so what
16:05 does he do what does the debranching
16:07 enzyme do he cuts the alpha4 gly ayic
16:09 bond right there from the glucose who's
16:12 connected with the alpha 1 16 and Alpha
16:14 14 he cuts that Bond then what does he
16:16 do he transfers those three groups of
16:18 glucose onto a longer chain what else
16:22 does he do he has a alpha6 glucosidase
16:24 activity so you can cut that Bond and
16:26 release free
16:28 glucose then what is the glycogen
16:30 phosphor l doing all he's doing is he's
16:32 reaching into a satal which is rich in
16:33 phosphates and transferring those
16:36 phosphates onto the one carbon of the
16:38 glucose in this polymer and forming
16:40 glucose one phosphate also you know what
16:42 else this enzyme has that's really
16:45 special you he's got ears and from his
16:47 ears he has this little earrings which
16:49 are made up of paradoxal phosphate so
16:52 here's his paradoxal phosphate earrings
16:53 these are important because paradoxal
16:54 phosphate is actually a component of
16:57 this transfer the transfer of these
16:59 phosphates onto these glucose molecules
17:01 to form glucose one phosphate so he's
17:03 extremely important and paradoxal
17:05 phosphate is actually a derivative
17:08 of vitamin
17:13 B6 okay so now we've done this process
17:15 we know exactly how glycogen is broken
17:16 down because we could keep going through
17:18 this but it all should make sense by
17:20 this point now we have to go to this
17:22 point what happens to these guys well
17:24 you know that free glucose it's not
17:26 chained down by any phosphat so where
17:27 could he
17:32 go he could go right out of the cell and
17:34 go where let's say over
17:37 here outside of this liver
17:41 cell there is a blood vessel if there's
17:43 a blood vessel right here what's going
17:45 to happen it's going to go right into
17:46 the blood when it goes right into the
17:48 bloodstream what's it going to do to the
17:51 actual glucose levels in the blood it's
17:52 going to increase the blood glucose
17:55 levels if it increases the blood glucose
17:56 levels what's going to happen then we
17:58 fixed the problem what was the problem
18:00 the the problem was that we had low
18:03 blood glucose levels and we fixed it so
18:04 now what is going to be here in the
18:09 blood this free glucose molecule okay
18:11 there's our glucose but it's only one
18:13 glucose right out of out of many many of
18:15 those glucose one phosphates we're
18:17 forming very little free glucose so
18:19 really insignificant amounts of this
18:20 glucose is really being contributed to
18:22 the blood glucose levels this guy is the
18:24 one who's accounting for significant
18:26 amounts of the blood glucose levels
18:29 because we're making tons of him okay so
18:32 what's happening to him okay so let's
18:33 say I take this glucose 1 phosphate
18:36 molecule you remember that enzyme guys
18:38 there was that special enzyme he was
18:41 taking the glucose one
18:44 phosphate and he was shifting that
18:46 phosphate from the one carbon to the six
18:48 carbon what was that enzyme guys that
18:50 enzyme that was stimulating this step
18:52 was called phospho
18:54 phospho
18:58 gluco mutase this enzyme is extremely special
18:59 special
19:00 because it's reversible remember how
19:03 this enzyme is also acting in the
19:04 reversible Direction converting glucose
19:06 6 phosphate into glucose 1 phosphate so
19:08 this is a reversible enzyme what's going
19:10 to be the result if I transfer the
19:12 phosph from the one carbon to the sixth
19:13 carbon I get
19:15 glucose six
19:18 phosphate so now I'm going to
19:20 have again what am I going to have over
19:21 here I'm going to have that phosphate
19:24 now on the six carbon so let's show that
19:26 over here I'm going to have my phosphate
19:27 and again just to get our carbon
19:30 straight guys this is one carbon six
19:31 carbon four
19:34 carbon this molecule is now called
19:36 glucose 6
19:38 phosphate here's where we run into an
19:40 issue glucose 6 phosphate can it be
19:42 transported out through this actual glut
19:47 transporter no okay so the liver and the
19:49 kidneys and certain types of parts of
19:51 the GI tract specifically the dadum have
19:54 a special type of enzyme only exclusive
19:58 to them in other words this enzyme this
20:01 enzy enzy here is extremely special this
20:03 enzyme is called glucose
20:05 glucose six
20:12 phosa Tas now I am going to be very very
20:13 picky with this because it's important
20:16 this glucose 6 phosphotase is only found
20:19 in specific organs the
20:22 liver the kidneys specifically in the
20:23 proximal convoluted
20:27 tubal and parts of the GI tract
20:30 particularly the dadum
20:32 this enzyme is not in the muscles so if
20:33 you do not have this enzyme in the
20:35 muscles can the muscle contribute to the
20:38 blood glucose levels no we will explain
20:40 that in the part of gluconeogenesis via
20:42 the glucose alanine cycle and the Corey
20:44 cycle how the muscle is actually getting
20:47 the glucose into the blood it's
20:49 indirectly okay for right now we're only
20:50 going to focus on the glucose 6
20:52 phosphate getting into the blood in the
20:54 liver so now let's take this glucose 6
20:57 phosphate and see what it's doing over
20:59 here okay so what is this guy right here
21:03 this is our specifically our
21:07 glucose six phosphate and how do I know
21:08 that again because this is the one
21:11 carbon four carbon six carbon this
21:13 glucose 6 phosphate is going to get
21:15 brought into this what is this structure
21:16 here you know this structure is actually
21:18 called the endoplasmic reticulum so this
21:20 is the endoplasmic reticulum
21:22 particularly the smooth
21:24 are what happens is this glucose 6
21:26 phosphate gets brought in through a glut
21:28 transporter and we particularly call
21:30 this blood transporter on the outside
21:33 that brings the glucose in we call it
21:35 T1 so now this glucose 6 phosphate is
21:38 going to be brought into the ER when
21:40 it's brought into the endoplasmic
21:42 reticulum it's acted on by a glucose 6
21:45 phosphatase so then look this guy is
21:47 going to react with the glucose 6
21:49 phosphatase enzyme what is that glucose
21:51 6 phosphatase enzyme going to do it's
21:55 going to rip out a phosphate so that
21:58 phosphate is actually going to be lost
22:01 what is this new molecule now this new
22:03 molecule that we formed here is now
22:06 going to be just free glucose and
22:07 where's that free glucose going to go
22:09 you know there's another transporter
22:11 that transports the glucose out it's
22:12 another glut transporter but we
22:14 specifically call it
22:17 T2 this guy is going to transport this free
22:18 free
22:21 glucose out of the endoplasmic reticulum
22:23 and back out into the cytoplasm and so
22:26 now I'm going to have my free glucose
22:28 molecule here where is this free glucose
22:31 molecule going to go now now it can go
22:33 out through the Transporters so it can
22:35 go out through the Transporters and then
22:39 where out into the blood and if it gets
22:41 put onto the
22:43 bloodstream and we're having a lot of
22:45 this activity occurring what's going to
22:46 happen to our blood glucose levels
22:49 eventually it's going to come back up So
22:51 eventually we're going to bring the
22:54 blood glucose levels back
22:56 up and try to be able to bring it back
23:01 to the homeostatic range now again this
23:03 activity of taking the glucose 6
23:05 phosphatase and acting on glucose 6
23:07 phosphate to make glucose can only occur
23:10 in the liver the kidneys and in the git
23:12 but primarily if you think about it we
23:13 didn't mention glycogenolysis occurring
23:15 within the kidneys or the git so we're
23:17 mainly only going to be focusing on this
23:20 activity that you just witnessed only in the
23:21 the
23:24 liver okay so now the reason why I'm
23:26 telling you that is because this enzyme
23:28 is again not in the muscles the muscles
23:31 can do glycogen alysis but they do not
23:33 have this enzyme so they cannot release
23:35 free glucose into the blood they get
23:37 stuck at glucose 6 phosphate so this is
23:38 where it gets stuck in the muscles let's
23:40 actually put that it's stuck in this
23:46 confirmation stuck like this in muscles
23:49 there's another way to get that
23:52 glucose into free glucose but it's an
23:54 indirect mechanism and we're going to
23:56 talk about it it's two cycles that we'll
23:58 discuss and we're going to talk talk
24:00 about the Corey
24:03 cycle and the glucose
24:06 glucose
24:08 alanine cycle we'll talk about this
24:11 whenever we go over gluconeogenesis
24:14 regulation okay all right guys so in
24:15 this video we covered a lot about the
24:18 glycogenolysis processes in the next
24:19 video we're going to go over a brief
24:22 concept of the actual regulation of this
24:25 actual process and different types of
24:26 clinical correlations that can come
24:27 whenever certain of these enzymes are
24:29 mutated all right Engineers I hope all
24:30 this made sense I hope you guys enjoyed
