In the next reaction, 3-phosphoglycerate is converted
into 2-phosphoglycerate by an enzyme known
as phosphoglycerate mutase.
And on the surface this looks like a very simple reaction but
there is actually a lot of complexity to this.
We are seeing the phosphate move from
position 3 to position 2. However, this
molecule has an intermediate that is created that is
important to consider and this intermediate is something
that has 2 phosphates. It's called 2,3-BPG.
Now one of the important
things about the 2,3-BPG
is it's a molecule that has a very
interesting affect on hemoglobin.
Hemoglobin is the oxygen
carrying protein in our blood
and hemoglobin can bind to 2,3-BPG.
And when it binds to 2,3-BPG,
hemoglobin lets go its oxygen.
Now that's important because
where do we want hemoglobin
letting go its oxygen. We want it
to be like go at places where a lot of metabolism is
going on because that's where the oxygen will be needed.
And when glycolysis is going a lot
one another things that it's making
as a by product is 2,3-BPG.
This is a good indicator to the body
that "Hey here is where I need the oxygen"
and hemoglobin is tuned to give it exactly.
Now the delta G zero prime for this reaction
is about 4.4 kJ/mol. It readily goes
either direction as we have seen
with some of the other reactions.
Well 2,3-BPG is a pretty important molecule as you
probably guess. So let's spend a little bit of time
understanding how it is
the cells make 2,3-BPG.
There are actually two ways
that cells can make this happen.
One of these is by using an intermediate
in the previous step of glycolysis.
Now that intermediate was 1,3-BPG
and in glycolysis you saw that it
was converted to 3-phosphoglycerate
and that generated a molecule of ATP.
But 1,3-BPG can also be converted by an enzyme
called bisphosphoglycerate mutase into 2,3-BPG.
Now this is actually the most
common way that cells will
make 2,3-BPG and this enzyme
is found in erythrocytes.
Erythrocytes being blood cells and this helps blood cells to
make 2,3-BPG to get rid of oxygen so that's very good.
2,3-BPG can be converted back into
3-phosphoglecrate as you can see here,
by the 2,3 bisphosphoglycerate phosphatase. Phosphatase
is an enzyme that takes the phosphate off of something.
So if that happens then what the cell
has done is that little side steps
around that substrate level phosphorylation
in the last step of glycolysis.
It doesn't affect our consideration
of glycolysis, however.
Now what I have been telling you
though is that 3-phosphoglycerate
can also make 2,3-bisphosphoglycerate
and the way that that happen is through the
unusual mechanism of action of phosphoglycerate
mutase, the enzyme that catalyzes
the conversion into 2-phosphoglycerate.
Now so let's think about this. In the
first reaction we saw two enzymes
that had to convert first to the 2,3-biphosphoglycerate,
and then back to the 3-phosphoglycerate.
Now we see one enzyme that is
making a by product that's 2,3-biphosphoglycerate.
That's a little confusing. But let me tell you how the enzyme
works and may be you will better understand how this all happens.
In the enzymatic mechanism of going from
3-phosphoglycerate to 2-phosphoglycerate,
one of the things that happens is the enzyme has the phosphate
on position 3 and it wants to get the phosphate to position 2.
Now you might logically think that the enzyme
grabs the phosphate and it moves it up one.
But that's not the way that a
mutase works. A mutase, instead,
starts with 3-phosphoglycerate, the phosphate on position 3,
and it puts a phosphate on position 2.
And then when it's done with that, it
takes the phosphate away from position 3
and it's left behind with
the phosphate on position 2.
So you can see that in the intermediate
phase the molecule has 2 phosphates on it.
A phosphate on position 3 and a phosphate on position 2
that's how 2,3-bisphosphoglycerate is an intermediate
in this pathway. Now 2,3-bisphosphoglycerate sometimes escapes the
enzyme and that's how it gets out and goes and flags
to the hemoglobin "Here is
where the oxygen is needed,"
because of an accident in the process.
If that accident doesn't happen then
2-phosphoglecrate is made
and there is no 2,3-BPG.
So the slower glycolysis is going, the less
likely the accident will be to happen.
In the next step of glycolysis, 2-phosphoglycerate
is converted into phosphoenolpyruvate
and the acronym for this one
is pretty easy. This calls PEP.
And you remember PEP because it has a lot of PEP.
PEP is an intermediate that has a tremendous amount of
energy as we shall see. It has a tremendous amount of PEP.
Now the enzyme that catalyzes
this reaction is known as enolase.
And in this reaction what's happening is
a water is being removed from 2-phosphoglycerate.
That's what creates the double bond that we see
in phosphoenolpyruvate and it's that double bond
that helps give all the
energy to this molecule.
The delta G zero prime for this reaction is about 1, so
it pretty much goes backwards and forwards
without any significant difficulties.
But PEP as we shall see is important
for the last step of glycolysis.
In the last step of glycolysis I'd like to call
this reaction the big bang of glycolysis
and there is a very good reason why. This reaction
is another substrate level phosphorylation.
We see that the PEP is converted into
another 3 carbon molecule called pyruvate
and in the process the phosphate
is transferred from PEP
onto ADP to make ATP. That means that PEP
has to have a lot of
energy to have that happen.
We saw the same thing with 1,3-bisphosphoglycerate
going to 3-phosphoglycerate.
But what's different here?
This substrate phosphorylation,
what I call the big bang, this
substrate level phosphorylation
has a delta G zero prime of -31.7 kJ/mol.
That's almost enough energy
to make a second ATP.
That's amazing. Well if we think about this "What
happens to energy that we don't use?"
"What happens when we have all this energy released?"
Well one of the by products of inefficiency,
whether that it's an automobile engine or it's a
cell, one of the by products of inefficiency is heat.
And heat is generated, the more we
run this reaction, the more we get.
So once you think about the
last time you went jogging,
and when you were out jogging, you got hot.
Why did you get hot? Well you got hot
because you had to run a
lot of metabolic pathways
and running those metabolic pathways,
like this reaction, generates heat.
Okay now this reaction because
the delta G zero prime is so negative
it's essentially irreversible.
This means that if the cell is going to
start with pyruvate and make glucose
it actually has to do a little dance around this pathway,
and we will see how that happens in pathway of gluconeogenesis.