Okay. Now the last inhibition I wanna
do, is a little hard to get your head
around and I mainly want to just introduce
what it does and the effects of this inhibitor.
This inhibitor, this type of inhibition
is called uncompetitive. An uncompetitive
is somewhere in between the two.
An uncompetitively inhibited reaction occurs by a
mechanism that you see on the screen.
The normal substrate binds to an enzyme as before.
But in the case of the uncompetitive inhibitor,
it only binds to the ES complex.
Now that ES complex is on
the way to becoming product
and so it's only binding at that point.
So the more ES complex we have
which is we are gonna have with more
substrate. The more ES complex we have
the more inhibited enzyme that we have.
Now that's kinda hard to get our heads twisted around.
We are gonna see, in fact, as we look at the plot
that's gonna be difficult
to conceptualize as well.
Let's take a look at the kinetics
now of an uncompetitive reaction
compared to that of an uninhibited reaction.
Again we are plotting V versus S,
as we have done before.
The orange plot is the uninhibited reaction, no inhibitor
present, and we see a normal hyperbolic plot.
When we plot the uncompetitive inhibited reaction; however,
we see something that's a little hard to get our heads around.
The confusion with the
uncompetitive reaction is that,
first of all, we see that it has a lower apparent
Vmax and it does have a low apparent Vmax.
And the other thing that's confusing
about this, is it has
a slightly higher velocity at lower concentrations.
And that happens actually; because, the uncompetitive
inhibitor favors the ES complex. It says if we are
increasing the percentage of the
enzyme present in the ES complex,
and that has the affect of apparently speeding up
the reactions which is why that first part of the curve,
the velocity for the uncompetitive reaction is higher
than it is for the reaction with no competitor.
Well when we do the plots we also see something
interesting that happens and that is
that the uncompetitive
reaction has a lower Km value.
So not only does the uncompetitive reaction at
high substrate concentrations have a lower velocity;
because, at higher substrate concentration we
will have a greater percentage of the enzyme in
ES complex which is greater target
for the uncompetitive inhibitor.
But we also see that the apparent Km of the enzyme
is decreased. And again this happens because the
the inhibitor is favoring the ES complex. It's making
it look like the enzyme is binding substrate better.
Well that confusing result is reflected in
what we see on a Lineweaver Burk plot.
On the Lineweaver Burk plot, what we have
is something that looks like this.
The green line, again, shows
the uninhibited reaction
with what we have seen before, that 1/Vmax
intercept on y-axis, and the -1/Km on the x-axis.
The Lineweaver Burk plot for
the uncompetitive reaction shows
a value higher on the y-axis for 1/Vmax
and that's reflect with the fact that the
Vmax has decreased so 1/Vmax has increased.
And we also see the x-axis
has moved further to the left,
meaning -1/Km has further away from 0 which
is what happens when we have a lower Km.