00:01
Now the metabolism of glycogen turns out to be
relatively simple compared to other metabolic pathways
that I have talked about in these presentations.
00:09
The complexity of glycogen
actually relates to its regulation.
00:13
We see on the screen a depiction of the
way in which glycogen is broken down.
00:18
So glycogen is broken down
by an enzyme called glycogen phosphorylase
and in many places this is abbreviated
and simply called phosphorylase.
00:28
As we will see there are a couple of different
forms of phosphorylase for consideration.
00:34
Now glycogen phosphorylase
is an interesting enzyme in the
way that it breaks glycogen down.
00:39
Many molecules like sugars and so forth
are broken down by hydrolysis using
water to break bonds.
00:48
Glycogen phosphorylase does
not use water. Instead
it uses phosphate as you can see here.
00:54
And so this is, instead of being called
a hydrolysis, is called a phosphorolysis.
00:58
Now that's not just not an
important thing of nomenclature.
01:02
But rather it actually is saving
the cell energy, as we shall see.
01:06
The phosphorolysis of glycogen
results in production of a molecule
called glucose-1-phosphate that
you can see on the lower left
and a glycogen that's
been reduced by one residue.
01:17
So what has happened in this catalytic
action, is that the enzyme has
broken the bond, the 1,4 bond
between the end of the glycogen chain.
01:26
Now it's important to recognize
that glycogen phosphorylase
works only on ends. It doesn't cut
in the middle, it works on ends
and it's subsequently chose
its way into a glycogen.
01:37
So one of the reasons that the branchedness as it
were of the glycogen is important is; because,
that the more ends there are, the more glycogen
phosphorylases can start on ends and subsequently release
a tremendous amount
of glucose very quickly.
01:53
We heard stories about somebody who is in
a terrifying situation. They do incredible
feats of lifting something heavy that
which seems otherwise impossible and
the ways in this happen actually
happens because of the branchedness
of glycogen which releases this burst of glucose
that people use to accomplish what they do.
02:14
Glucose-1-phosphate is readily
turned into glucose-6-phosphate
by the enzyme phosphoglucomutase.
02:20
Now this is a reversible
reaction, as you can see.
02:23
The significance of the
reaction though is that glucose-6-phosphate
is produced and if we remember
we started with a glycogen
that had glucose that had no phosphates on them.
02:34
We have at this point an intermediate in glycolysis,
glucose-6-phosphate, that does have a phosphate on there.
02:40
And that phosphate got on there
not not by the use of ATP.
02:44
If you recall from the
glycolysis presentations
hexokinase uses an ATP to put a
phosphate onto glucose to make glucose-6-phosphate.
02:54
Here this phosphate got put
onto the glucose from the glycogen
by using a phosphorylases
reaction that did not require ATP.
03:02
This saves the cell energy.
03:04
And the energy for putting that phosphate
on actually came from the breaking
of the 1,4 bond by
the glycogen phosphorylase.
03:11
So cells are very efficient. Cells use
whatever they have available to them
to do things as efficiently as possible
and this is a very good example.
03:21
Now glycogen breakdown proceeds, as I said, by
the action of glycogen
phosphorylase working from ends
and I also noted that glycogen
is a very branch molecule.
03:31
We can see on the screen
here a branch of glycogen
and learn a little bit about the way
that glycogen phosphorylase works.
03:38
You see on the top, the branch,
and you see the end of
the molecule where we have
10 different blue residues
that are shown on the left.
03:46
Those 10 residues are all
targets for glycogen phosphorylase.
03:51
So as the enzyme acts, it
goes through and it releases
those 10 subsequently in the reaction that
I showed in the beginning of this lecture.
04:00
It takes 10 phosphates and 10
glucose-1-phosphate are produced as a result.
04:05
Now at that point, glycogen
phosphorylase won't go any further.
04:09
So glycogen phosphorylase
has a limit in how close
to a branch it will work.
04:15
You know that the branch is at the base of
the yellow molecule, shown on the very top.
04:21
Now as we moved down to the second part,
you see we have changed the color of those
glucose. So that three of
them are still in yellow
and 1 is now shown in the sort of orange
color and there is a reason for that.
04:32
There is an enzyme called debranching enzyme that
plays the second role in breaking down glycogen.
04:38
Debranching enzyme takes the 3 yellow
residues that you see in the square
and transfers them down
to the chain below.
04:46
So because glycogen phosphorylase can only
work within about 4 units of a branch
this debranching enzyme plays
the important role of rearranging
molecules so the glycogen phosphorylase will
have additional substrates to work on.
05:00
Debranching enzyme is also interesting in another
respect that is it actually catalyzes two different reactions.
05:06
The first reaction you
can see on the screen
which is the transfer of the 3 residues
of glucose down to the lower chain.
05:13
What's left behind is that
single molecule that is shown
above the main chain.
05:19
That's single molecule has that α-1,6 bond
that's part of the glycogen branching.
05:28
That last molecule is removed
by a hydrolysis reaction. So
water is actually used to release that and glycogen
debranching enzyme catalyzes that reaction.
05:39
So it's a very flexible, it's a very
remarkable enzyme in doing what it does.
05:43
But because of that you can see that
an unbranched form is now left behind
and glycogen phosphorylase can come back in
and continue the phosphorolysis
that it was doing originally.
05:56
I should also note one of the
point here and that is that
the release here of glucose is the only place in
glycogen metabolism where free glucose is released.
06:04
All other releases are glucose-1-phosphate.