Special cases: Histidine, proline, glycine, cysteine | MCAT | Khan Academy

Special cases: Histidine, proline, glycine, cysteine | MCAT | Khan Academy

September 10, 2019 7 By Kody Olson


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.