Special cases: Histidine, proline, glycine, cysteine Video Lecture

Hey.
So welcome to the
Amino Acids Show.
And this show is going
to be featuring just 4
of the 20 amino acids.
And those amino acids are
histidine, proline, glycine,
and cysteine.
And these four
amino acids deserve
sort of an extra
time in the spotlight
because they each have a side
chain that sort of sets it
apart from the rest.
And so let's go
through one-by-one
and see what exactly these
side chains are all about.
So first up we have
histidine, and I've
drawn the structure of
histidine for you here.
And here is the backbone
of the amino acid.
So this is the same for
all the amino acids.
And then, you see here is
the side chain of histidine.
So what is so special about
histidine, then, with this side
chain?
Well, as it turns out, this side
chain has a pKa of around 6.5.
And this turns out to be really
close to physiological pH,
which is right around 7.4.
So what does this
really mean-- to have
a pKa that's close
to physiological pH?
Well, recall that, at a pH
below an amino acid's pKa,
the amino acid will exist in
a protonated-- or positively
charged-- form.
And at a pH above
an amino acid's pKa,
it will exist in
deprotonated form.
Now, since the
physiological pH--
which is the pH of the fluid
within our own bodies--
is roughly equal to
the pKa of histidine,
then histidine's
going to exist in
both protonated and
deprotonated forms.
So this makes it a
particularly useful amino acid
to have at the active
site of a protein
where it can both stabilize
or destabilize a substrate.
So next step we have
proline and glycine.
If we go ahead and take
a closer look at proline,
we have the backbone
structure here-- just
like all the other amino acids.
But then, you can see that the
side chain is this alkyl group
that wraps around and
forms a second covalent
bond with the nitrogen
atom of the backbone.
And so we say that proline has
a secondary alpha amino group.
And so this is just
referring to the fact
that the side chain forms a
second bond with the alpha
nitrogen-- the nitrogen in the
backbone-- of this amino acid.
Now, let's come over here
and take a look at glycine.
Here we have the backbone
of the glycine molecule.
And then, here we
have the side chain.
And the side chain
for glycine is
the simplest of all side chains.
It is just 1 hydrogen atom.
And I've drawn it out
in wedge-and-dash form
here to help emphasize
how-- because the side
chain of glycine is
a hydrogen atom--
you have a duplication of
atoms coming off of this carbon
here-- the alpha carbon.
And so now this carbon is
no longer a chiral carbon.
So we'll write that here.
No chiral alpha carbon.
And this kind of sets
it apart from the rest
of the amino acids because
the rest of the amino acids
do have a chiral carbon--
meaning optical activity
under plane-polarized light.
And glycine is also considered
to be very flexible because it
just has this little hydrogen
atom as its side chain.
And so there's a
lot of free rotation
around this alpha carbon.
So we also consider it
to be very flexible.
So why are these two amino
acids groups together?
Well, they both play a role in
disrupting a particular pattern
found in secondary
protein structure called
the alpha helix.
And an alpha helix
is just a coiled up
polypeptide chain that
kind of looks like this.
Now, because of its
secondary alpha amino group,
proline introduces kinks
into this alpha helix.
And it ends up
looking like this.
And also, since
glycine is so flexible
around its alpha carbon, it
tends to do the same thing.
And thus both of
these amino acids
are known as alpha
helix breakers.
So last but not least,
we have cysteine.
And here's the backbone again.
And then, here is
our side chain.
And the side chain for cysteine
has a special thiol group.
And all thiol is
really referring
to is the sulfur and the
hydrogen at the end there.
So cysteines have
this neat little trick
where, if they're
in close proximity
with each other within
a polypeptide chain
or even between two different
polypeptide chains, then
their side chains can
form a bond together
between the two sulphur atoms
called a disulfide bridge.
So let's bring up 2
cysteine amino acids here.
And I've shown them as
isolated amino acids,
but remember that they are part
of a greater polypeptide chain.
And the formation of
the disulfide bridge
occurs separate
from the backbone.
It is just between
the side chains.
The cysteine at the
top is flipped over
to bring its side chain
in close proximity
with the second
cysteine below it.
And then, the bridge forms
between the two sulphur atoms.
So before we go over how a
disulfide bridge is formed,
let's do a quick little
review of redox reactions.
And really, what
you want to remember
is the mnemonic OIL RIG.
And that's to mind you
that, in oxidation, you
have a loss of electrons.
So oxidation is loss.
And in reduction, you
have a gain of electrons.
So reduction is gain.
So remembering
that will help you
understand the disulfide
bridge formation.
So going back to
our 2 cysteines.
If you look closely
at their side chains,
the thiols are existing
in reduced form.
So you're going to
find these tholes
in a reducing environment.
Now, say those cysteines end
up in an oxidizing environment.
In that case, you would see
the loss of these hydrogens
and then the formation of a
bond between these two sulphur
groups, which looks like this.
So this here is your
disulfide bridge.
So when do you see
cysteines going solo,
kind of like you see here in
the separate thiol group form?
And when do you see them
forming these disulfide bridges?
Well, it turns out that it
depends a little bit on what
the rest of the environment
around them is like.
And as it turns
out, the exterior
of the cell or the
extracellular space
is an oxidizing environment.
So I'll write that down here.
So the extracellular
space will favor
the formation of
disulfide bridges.
But in the intracellular
space, you're
more likely to find a
reducing environment.
So I'll write that down here.
And the way that I like
to keep this straight
is that I kind of think of
how the interior of the cell
has these little molecules
called antioxidants.
And these antioxidants,
which-- you can kind of
tell by the name of it--
stifle any oxidizing reactions.
And so they keep the
intracellular space
a reducing environment.
So you might have seen
cysteine spelled without an e,
like this.
And you're probably
thinking to yourself,
is it cysteine with an e?
Is it cysteine without an e?
Is it cystine?
Which one is it?
I'm so confused.
There are actually two official
ways of spelling cysteine.
The version with the
e refers to cysteine
when it's in its reduced form.
And the version
without the e refers
to cystine when it
has been oxidized.
And the way I remember
this is by picturing
that the e stands for electrons.
And so you have
the electrons when
you're in the reduced form.
And then, you don't
have the e for electrons
when you're in
the oxidized form.
So hopefully that helps you keep
things straight a little bit.