Glycogenolysis is the metabolic process of breaking down stored glycogen into glucose to increase blood glucose levels, primarily occurring in the liver and muscles in response to low blood sugar.
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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
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
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
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
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
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
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
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
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
glyco cdic
cdic
Bond if I count one two three four this
guy right here I'm going to put a mark right
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
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
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
six
carbon six carbon there and again give
them the smiley faces so we know orientation
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
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
glucose transfer
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
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
phospho
gluco mutase this enzyme is extremely special
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
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
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
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
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
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