Now, we are going to continue our discussion
of bio-chemical interactions by discussing
enzymes. The aims of this particular lecture
are to introduce enzymes and identify why
they are important drug targets.
We will also be considering enzyme inhibitors
and show you how to categorise them as reversible/irreversible
and either competitive or non-competitive.
We will also be considering the mode of action
in the basic sense of aspirin, a COX-1 inhibitor.
So, what are enzymes? As you can appreciate,
as per in the laboratory, many many reactions
occur within the body. They take place in
aqueous solution. They... enzymes themselves
must work efficiently and in excellent yields
and they must be reliable.
And the role of an enzyme is essentially a
catalyst. All be it a biological catalyst
that lowers the activation energy of a specific
So, how do these factors differ from lab based
organic chemistry? In order for biological
chemistry to work, these complex catalysts
called enzymes control specific reactions.
And what is the definition of a catalyst?
Putting it simply, a catalyst is something
which increases the rate of a specific reaction
by lowering the activation energy. And in
the case of enzymes, all there are is biological
equivalence of these catalysts.
Let’s have a look at an example of an enzyme
in a specific reaction. For example, the reaction
of carbon dioxide with water is necessary
to remove carbon dioxide from tissues into
the blood stream to be returned to the lungs.
Let’s have a look at that reaction now. Carbon
dioxide plus water giving hydrogen carbonate
plus H+. This reaction, if just left on its
own, would be far far too slow to sustain
life, if it were not catalysed. And this
is where the carbonic anhydrase enzyme speeds
up this reaction rate by over 1 million times.
This you can appreciate. It’s a substantial
improvement on what would normally happen
and represents, in many respects, how these
biological catalysts, aside from having selectivity,
which is far better than anything we see in
the laboratory, also, can speed up these reactions
by a substantial rate.
Note, most enzymes such as the carbonic anhydrase
have the suffix “ase” at the end of their
name. And we will see this a little bit later
So, enzymes themselves, what are they? Well,
they are made up of proteins or at least they
are a special class of protein.
What they do, as we will see in the diagram
in the next slide, is they bind a substrate
or the substrate given is the reactants, in
this particular case, bind other molecules
where appropriate. These are known as cofactors.
And if you look at a lot of the vitamins:
Vitamin A and B and so forth, they are used
as cofactors in many of these biological reactions.
And these help... these would be the reagents
in a laboratory synthesis.
The reaction is carried out and then the product
is released, so, in many respects, exactly
as you would find in an organic chemistry
Let’s have a look in a bit more detail. Here
we have a cartoon representation of an enzyme,
shown in green, and a substrate, shown as
red, joined to a blue ellipse.
The first role is to bind the particular substrate
to the enzyme, which is shown in the next
diagram. The reaction then takes place. In
this case, this is a lysis reaction. What
is it doing is it’s separating one component
from another. And finally, the enzyme, in
this case, releases those two products. So,
in this particular case, what we are looking
at is a reaction which splits two things apart
or lyases them.
Let’s have a look at a particular example
of a lysis reaction, in this case, back to
the selectivity that I was eluding to earlier.
Here we have a glucose, specifically an alpha
methyl glucose. This is known as an acetal.
Remember, in previous lectures, we have talked
about hemiacetal, but where we actually have
two alcohol groups attached to a central carbon,
it’s known as an acetal.
Pay particular attention to the stereochemical
difference between the alpha glucose methyl
ether and the beta glucose methyl ether, which
is shown at the bottom.
The difference in stereochemistry effectively
means that only the alpha glucosidase enzyme
is able to hydrolyse that acetal resulting
in the formation of a free alpha glucose and
methanol. The enzyme alpha glucosidase is
unable to break down the beta glucose acetal
equivalent and their reaction occurs.
This, for example, in a very basic sense,
is the reason why human beings cannot break
down things like tree bark and so forth because
the cellulose from which it is constituted
is made up of beta glucose units rather than
alpha glucose units. And therefore, we lack
the enzymes to be able to break it down to
the sugar components which we then use as
part of the glycolysis in citric acid and
electron transport chain.
An enzyme, as I have said, will only catalyse
a certain type of reaction using certain substrates.
In this particular scenario, this is a stereochemical
selectivity for one particular, if you like,
[Unaware 00:06:05] over the other.