The reaction of gluconeogenesis are shown on
the screen here and this is a kind of a complicated
pathway. So let's try to break it down a little bit.
There are 7 enzymes, as I said, that are common between
the two and they are shown in dark green here.
I won't talk about those; because, the reactions
of gluconeogenesis that use these enzymes
are simply running a reactions
of glycolysis backwards.
The enzymes of gluconeogenesis
that are different from glycolysis
I wanna spend a little bit of time of talking about;
because, they have some considerations for us.
The first of these reactions that I will
talk about is the reaction catalyzed
by the enzyme known as pyruvate carboxylase,
you can see it on the lower right,
and in this reaction, pyruvate is being converted
into oxaloacetate. What does that mean?
Pyruvate has 3 carbons
and for this reaction a carbon is actually
added to pyruvate. That comes from the
bicarbonate that you can see
at the bottom of that image.
Now ATP energy is required
in order to make this happen
and so we produced ADP in the process.
These are the intermediates that
we are talking about right here.
Now why is the cell doing this? Why is the cell
making oxaloacetate? Why didn't it just reverse
the reaction to go from
pyurvate to phosphoenolpyurate?
Well that was the big bang of glycolysis
and that reaction is essentially irreversible.
The cell is having to take a two step around that.
The first step of which we just now covered.
The first step
using the enzyme pyruvate carboxylase
happens in the mitochondrion.
The first step happens in the mitochondria is
physically isolated from the reactions that are
ocurring in the cytoplasm.
After that reaction occurs in the mitochondrion,
the oxaloacetate that's produced
is moved out to the cytoplasm.
Now here is the reaction
that you just saw.
The pyruvate carboxylase is an
enzyme that uses a co-enzyme.
Now co-enzymes are important helpers for enzymes.
And what they usually do is
they have a specific function.
This specific function of pyruvate carboxylase is to
grab hold of a carbon and put it onto something
and that's what's happening here.
The 3-carbon-intermediate-pyruvate is becoming
Biotin is helping pyruvate
carboxylase to do this.
Now after that reaction
of making oxaloacetate,
the oxaloacetate, as I said, is moved out
to the cytoplasm. And in the cytoplasm
there is an enzyme called phosphoenolpyruvate
carboxykinase, yeah mouth full of name.
PEPCK is actually one of the enzymes
that is regulated at the gene level.
Meaning that most of our cells of
our body won't make this enzyme.
And if they don't make this enzyme,
then they can't do the next step
in gluconeogenesis. So we can see how
gene regulation helps to
control a metabolic pathway.
Cells that's don't have PEPCK, as we call it,
can't go through gluconeogenesis
because they can't catalyzes reaction.
But this enzyme is activated and made
in liver and kidney cells
where gluconeogenesis occurs.
Well, let's look at the reaction. In the
reaction, that is happening right here.
This reaction converts oxaloacetate, OAA,
And notice that it's using the triphosphate
known as GTP to make it all happen.
The GTP has the same energy as ATP.
So in essence in going from pyruvate
back to PEP
we had to use two triphosphates to make that happen.
That big bang was pretty hard to overcome.
We have just seen the two steps. The cells have
to go through to go form pyruvate back to PEP.
The next steps will actually be quite easy for
students to learn and the reason is because
they are simply the reversal of the reactions
that were catalyzed in the glycolysis pathway.
The very same enzymes run
in the backwards direction
go from PEP back to fructose-1,6-bisphosphate.
That fructose-1,6-bisphosphate; however,
there is a different enzyme that's used to make gluconeogenesis
work and there is a very good reason for that.
The next reaction of gluconeogenesis
is catalyzed not as the
reverse of the PFK reaction.
The first reason of that is not
done is because PFK is catalyzing
a reaction that is energetically favorable
in the direction of glycolysis and
it's difficult to overcome that.
So rather than have to go through a 2 step,
the cells are simply bypassing, as we will see here.
The second is that PFK is setup
very well to regulate glycolysis
but it's useful to have a different enzyme
to regulate gluconeogenesis and we will
see how that happens in just a little bit.
So the enzyme that is used
in gluconeogenesis instead of
the enzyme that's used in glycolysis,
the enzyme gluconeogenesis is called FBPase,
as you see in the abbreviation,
or its longer name is
Now this reaction is not
the reverse of the
reaction in glycolysis.
And the reason it's not is because in glycolysis the
PKF enzyme required ATP to put the phosphate on.
In the reverse reaction, all we are
doing is clipping the phosphate off.
We are not regenerating the ATP
that was used in glycolysis.
So the cell is actually cheating here again.
The reason it's cheating, it's not
completely reversing the reaction
even though the intermediate
fructose-6-phosphate is still generated.
What the cell is doing is it's using that
high energy of the phosphate on position 1
to drive this reaction and
all it takes is water.
To go from fructose-6-phosophate to the end of the
gluconeogenesis pathway is now pretty easy.
What happen is, first of all, the fructose-6-phosophate
is converted back to the glucose-6-phosophate
by a reversal of the glycolysis
pathway as we saw before.
That leads us to glucose-6-phosophate that needs
to be converted into glucose.
And here the cell uses the same trick it used
in converting fructose-1,6-bisphosophate
It uses a different enzyme.
The enzyme here is called
G6Pase or glucose-6-phosphatase.
And the reaction that is catalyzing is simply the
clipping off of the phosphate from position 1.
Notice again this is not the
reversal of the hexokinase pathway
the cheating that the cell is doing is, it's not recreating
the ATP that would be required for the reversal of the reaction.
So the energy is realized
by not regenerating that ATP.
This reaction is another reaction
that does not occur in the cytoplasm.
This reaction occurs in the
endoplasmic reticulum. So, again,
we see some sequestration that's happening
and we also sort of see why
all those other reactions
were occurring in the cytoplasm and that was because many
of them were using the same enzymes as glycolysis.