Now, I’d like to bring you on to metal containing
enzymes. Metal-activated enzymes associate
loosely with ions. And they usually come from
the group 1 or group 2 part of the periodic
Although some of them, as we will see, such
as zinc or iron containing enzymes come from
the transition metal. And they use these ions
to adopt a specific structure or shapes, sometimes
bringing together more than one protein.
Metalloenzymes is the general name for these
and they contain tightly bound metals usually
from the transition block which can bind substrates
in specific orientations and carry out RedOx
reactions with changes in the metal oxidation
state. It’s also possible for them to stabilise
negative charges. Around a third of all enzymes
require the presence of a metal ion for activity.
So, let’s have a particular look at our friend
carbonic anhydrase. This is the enzyme, if
you remember, that’s is responsible for
the conversion of carbon dioxide and water
into hydrogen carbonate.
Here, you can see a diagram which shows the
orientation of different amino acid residues
in relation to zinc, which remember is found
as a transition metal within the periodic
table, in order to hold these particular groups
Note the coordination of the histidine 96
residue, the histidine 94 residue and the
histidine 119 residue. So, all of those key
histidine residues are donating electrons
into the shell of the zinc ion in the center.
Also, note the coordination with water that's
shown here as H2O. This is very important
in relation to how it coordinates with the
carbon dioxide. So, how does it actually work?
Let’s go through it step by step.
Here we have, in the left hand side corner,
a zinc which is tetrahedrally coordinated
to the imidazole rings of 3 histidine residues
and if you are unsure as to what we mean by
that, I recommend that you look up histidine
as an amino acid.
And you will see that you are looking at the
imidazole nitrogen containing cyclic structure
which donates electrons into the zinc positively
charged cation and holds it together.
In the first instance, what we have is water
coordinated to the Zn2+, the zinc ion, as
we saw in the previous diagram. What happens
in this scenario is the coordination makes
the one of the protons on the water more labile
and this results in the coordination effectively
of a hydroxyl group to the zinc 2+ resulting
in the loss of H+, as we can see.
Now, we have a negative charge on that oxygen,
this can then nucleophilically attack our
carbon dioxide, shown here on the right hand
side. Bear in mind, if you recall back when
we were talking about dipoles, it’s important
to realise that where we have those two very
electronegative oxygens pulling electron density
away from that carbon, that carbon itself
is going to be quite delta positive.
This means the negative charge on the oxygen
would find it easy to carry out a nucleophilic
attack on that carbon breaking open that carbon
oxygen double bond.
Once that happens, you have a coordination
effect, as you can see here, where you have
the oxygen, now covalently bound to the carbon
of the carbon dioxide. And this ultimately
results in the release of hydrogen carbonate.
Note now, the complex iron CO3- is only loosely
bound by that dative covalent bond shown
as a dash between the zinc 2+ and the oxygen
and HCO3 can be produced.
Enzymes and drugs.
So, not only are enzymes important in maintaining
reactions within the body, everything from,
as I said, glycolysis, metabolism, catabolism
and so forth, they are also important in regulating
Enzymes bring about drug metabolism and of particular
importance are the cyctochrome P-450 mixed
function oxidases that are often found in
Some enzymes can be used to activate pro-drugs,
as we have already said and as we will see
in greater detail a little later on. Enzymes
themselves can sometimes be drug targets.
And some disease states arise through the
malfunctioning of a specific enzyme.
If the body is, for example, attacked by foreign
invaders, e.g. micro-organisms or viruses
then these can be halted by the interference
with their enzymes.