Okay so what I am going to do now
is take you through step by step
the individual reactions of glycolysis ,
discuss a little bit about the enzymes
and then some additional considerations
for each reaction as appropriate.
In the first reaction we see the glucose
being converted into glucose-6-phosphate.
This is a very simple reaction catalyze
by an enzyme called hexokinase.
You can see that this is one of
reactions that requires an input
of ATP in order to jump start the process.
And the reason that this happens is that
the phosphorylation of glucose by itself
is not energetically favorable. So
the reaction is coupled to an energetically favorable
reaction which is the hydrolysis of ATP
to make ADP and of-course the other
product being glucose-6-phosphate.
This reaction involves the
carbon number 6 of a glucose
as you can see here that becomes attached to the phosphate
which is carbon number 6 shown in the glucose-6-phosphate.
This is a regulated step of glycolysis.
Now glycolysis has a very unusual
system of regulation and there are
some reasons why that's the case.
But glycolysis as we will see has
three points of regulation in it
and this first step is one of
those point of regulation.
Hexokinase, the enzyme, is actually
inhibited by it's product.
So as it's product accumulates in cells,
hexokinase will quit running this reaction.
Now that's important because if a
cell is, for example, making glucose
what will happen is glucose-6-phosphate's
concentration is increased.
And if glucose-6-phosphate
concentration is increasing,
then there is no reason to
continue making more of it.
Hexokinase gets shut off in the process.
The delta G zero prime for this
reaction is very favorable because
of the hydrolysis of ATP being about
-16.7 kJ/mol and it goes forward readily.
Now hexokinase is an interesting enzyme it's
founds inversely all cells of the body
it's not specific to glucose
and that's why it's called
hexokinase instead of glucokinase.
The hexo referring to 6 and the 6 that
it's referring to are 6 carbon sugars.
So for example hexokinase could also work on a 6 carbon
sugar like galactose and make galactose-6-phosphate.
Glucokinase which is a related enzyme
has a higher Km which means that
it requires a greater amount of glucose to
work on and glucokinase is found in the liver.
Now that turns out to be important
because glucose is made in the liver
and so with glucokinase being in
the liver and having a higher Km
it means that glucokinase
will not be active typically
under the glucose concentrations where the liver is
making glucose and that balance is really important.
As I said the hexokinase is
inhibited by it's product
and one other thing about the
hexokinase is very interesting.
Hexokinase has a mechanism of action that
involves what I'd like to describe as jaws.
And these jaws looks sort of
like this before the enzyme
has bound to it's substrate.
The two substrates that hexokinase
binds to are ATP and glucose.
And in this reaction what happens
is, once the enzyme has bound
the ATP in my top hand and the
glucose in my bottom hand
We see the Koshland Induced Fit come into the play
because the enzyme goes through clamping
down of the jaws like I am showing here,
which brings the ATP and the glucose
into very close physical proximity.
This facilitates the movement of
the phosphate from ATP to glucose.
At that point the jaws open and the
ADP and glucose-6-phosphate are released.
In the second reaction of glycolysis this
simple reaction is catalyzed by an enzyme called
phosphoglucoisomerase and as it's name suggest
it's catalyzing an isomerisation.
The isomerisation is simply a rearrangement
of the glucose-6-phosphate
into a different sugar
And though they look very different, fructose and
glucose are fairly closely related to each other.
This is a readily reversible reaction.
It can go forwards and it can go backwards
and the direction that it proceeds will
be a function of concentration of these.
Now reversible reactions are
things to think about because
when we go to make glucose in
the process of gluconeogenesis,
some of the reactions are run in the reverse
reaction. This is one of those reactions.