- [Voiceover] So today we're gonna learn about covalent
modifications to enzymes.
But first, let's review the idea that enzymes
make reactions go faster.
And looking at a reaction coordinate diagram
you notice that enzymes do this by lowering
the reaction's activation energy.
Also, before we talk about covalently modified
enzymes, I want to remind you
that not all enzymes are proteins.
And often, when we think of enzymes
we think of proteins,
which are amino acid polymers
with primary, secondary, tertiary,
and quadrinary structures.
But there are also many different kinds of enzymes
that aren't proteins.
Inorganic metals, like magnesium,
or small organic molecules, like flavin,
can also act as enzymes.
But for the purposes of this discussion
we're going to focus on the proteins.
And to be clear, when we say covalent modifications,
we refer to modifications to a protein
that involve forming or breaking covalent bonds.
Now there are tons of different covalent modifications
that we can observe.
So I'm only gonna touch on a select few
to get the point across.
And the first category of covalent modifications
I want to talk about
are small post-translational modifications.
Now, when I say translation,
I'm referring to the process of translation
where amino acid polymers are synthesized.
And when I say post-translation,
I refer to events that take place
after that initial synthesis.
Now when I say small,
all I'm referring to are modifications
that involve small functional groups
being added or removed from an enzyme.
And again, there are many different types of these
but I'm just gonna touch on three.
So methylation is a modification of a protein
that involves the addition of a methyl group,
or CH3, to a protein.
Acetylation involves the addition
of an acetyl group.
And glycosylation involves the addition
of a sugar molecule.
And these are just three examples
of a huge list.
And these modifications, although small,
can have pretty significant impacts
on protein as a whole.
And to discuss this, I want to mention the example
of acetylation of a lysine residue on a protein.
So as you many know,
lysine is an amino acid
that has an extra amino group on its side chain
that can act as a base
and carry a positive charge.
If we were to acetylate this lysine residue
and add an acetyl group
to the amino and nitrogen,
which is a covalent modification,
the electron withdrawing effect of the acetyl group
will prevent that nitrogen from carrying a positive charge,
and modify the behavior of that amino acid.
The loss of that positive charge
can change a few properties of the amino acid,
including changes to the lysine's acidity
and basicity, since it can no longer exchange protons,
as well.
And it will also influence lysines
electrostatic interactions with other charged molecules,
since it's lost that positive charge.
So even a small modification,
like the addition of a cell group,
can have significant impacts on the protein overall.
Moving on, I want to discuss another way
in which covalent modifications of enzymes is relevant.
And that's in reference to zymogens.
Now a zymogen is an inactive form of an enzyme
that requires a covalent modification
in order to become active.
And a big example of these zymogens in biology
are the digestive enzymes of the pancreas releases
so that you can digest food.
One of the enzymes of the pancreas releases
is called trypsinogen, which is a zymogen
as indicated by the ogen suffix.
Now this is an inactive form of a chrodeus enzyme
that is shipped to the intestine.
And once in the intestine, it's covalently modified
by an enzyme called enterokinase
which converts it to its active form trypsin.
Now this is to prevent trypsin from breaking down proteins
that we need in the pancreas
since it's inactive at that point as trypsinogen.
And only allows it to break proteins
down in the intestine
after it's encountered enterokinase.
Notice how you can distinguish zymogens
from their active form by their name,
zymogens have ogen added to the end of them.
Now the last example of covalently modified enzymes
that I want to discuss
is the subject of suicide inhibition.
Now, when we think of enzymatic inhibition
we usually think of competetive, non-competetitve,
and uncompetetive inhibitors
which follows certain patterns in terms of
their effects on enzyme kinetics.
But there's another type of inhibitor
that's a little different,
and this is the suicide inhibitor.
Suicide inhibitors covalently bind the enzyme
and prevent it from catalyzing reactions.
And what's interesting is that since these inhibitors
form covalent linkages to the proteins,
they rarely unbind,
which is why we call them suicide inhibitors.
Since after they bind, that's it for them.
And this is what distinguishes this type
of inhibitor from the other three
that you might be familiar with.
So, what did we learn?
Well, we talked about three very different things today
that all have to do with covalent modifications
to enzymes.
First, we talked about
small post-translational modifications,
like methylation, acetylation, and glycosylation.
Second, we discussed zymogens,
inactive proteins that require covalent modification
to become active.
And finally we talked about suicide inhibitors,
which are enzyme inhibitors that
permanently bind their target.