>> Hello, and welcome to The Penguin Prof Channel.
In today's episode, we are going to tackle tautomeric shifts.
That's the explanation for why sometimes nucleobases misbehave.
You can get adenine pairing with cytosine, for example.
We got to talk about tautomers, and we're going to talk
about what happens when you have a tautomeric shift.
Yeah, we're going there.
All right.
You know the drill.
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All right.
Early on, you were taught that the bases are
like puzzle pieces, and the reason why adenine
and thymine always go together and cytosine
and guanine always go together is
because that's just how they fit, and that's true.
Later in your career, you were shown why they fit the way
they do.
It has to do with hydrogen bonds.
Adenine and thymine are held together
by two hydrogen bonds while cytosine
and guanine are held together by three.
And wow, isn't that beautiful?
And everything makes sense, but then they hit you with this.
Oh my gosh, there can be changes and mutations, and purines
and pyrimidines can even be switched out
and they don't tell you why, and it's all very frustrating
and most textbooks don't explain it.
But you came to the right place.
We're going to talk about how that happens.
First, we have to understand what structural
or constitutional isomers are.
They're molecules with the same molecular formula,
but they're connected differently.
Look, an example.
Here's butane, C4H10.
Look. this is isobutane.
It's also C4H10.
So the number of carbons and hydrogens is the same,
but the structure is different,
and this is an example of a chain isomerism.
Let's look at another one.
Here's one some of you may know.
That's ethanol, and this is dimethyl ether.
That's toxic.
You find it in propellants and things
like hairspray and bug spray.
These are also structural isomers,
and we call them functional group isomers
because the functional groups the stick off
of the chain are different.
Okay, here's a quick analogy for you.
Okay, we're gonna look at LEGO --
okay, we're going to look at Building Bricks.
And you know how -- oh, God, the lawyers.
You know how sometimes you get a kit
and you can build two different toys from the same kit?
That would be a great example of a structural isomer.
Okay, so we got it: different connectivity.
Now, tautomers, they are structural isomers.
They're a subset, but they can interconvert
between the two forms and they exist in an equilibrium.
Okay, let's look.
Here is acetone.
You know acetone.
Acetone is in nail polish remover and paint thinner.
Acetone exists in two different forms.
This form is called the keto form,
so named because of the ketone functional group right there.
It is in equilibrium with an enol form,
so named because there's an alkene
and an alcohol group right here.
So you get the ene, and then you get the ol.
This is also a functional group isomerism,
and the idea is you want to look at that arrow there,
this little equilibrium symbol, and it shows you
which form is dominant.
So the keto form dominates over the enol form, but the idea is,
they are tautomers because there are these two different
structural forms, but they interconvert.
Okay, so in my analogy -- it's going to get real weird here --
your brick toy is going to spontaneously shift
between the two options all by itself.
Okay, that's pretty crazy, but you get the idea.
This understanding is going to allow us to get
at these nucleobases and see what happens
when they undergo a tautomeric shift like that.
All right, so here's what can happen.
In their most common forms, adenine and cytosine exist
in what we call an amino form,
but when they undergo a tautomeric shift,
they become a different shape, and we call them an imino form,
imino with an I, and I'm going to designate that with a star,
and they exist in an equilibrium between these forms.
Notice again, these equilibrium arrows show you
which form is the dominant form.
In this case, the amino form of each.
All right, we got two more bases: guanine and thymine.
These are examples of that keto enol isomerism
that we saw earlier with acetone.
Same exact idea.
Did you notice?
This is the ketone group,
and these are the enol groups over there.
Hopefully they're starting to look a little familiar.
Same idea.
The keto form dominates over the enol form.
Okay, so now you're ready to see how these play together.
So the tautomer of cytosine, C-star, binds with adenine,
and the tautomer of thymine,
that's the T-star, binds with guanine.
This explains why they do this, guys.
The tautomer of adenine binds with cytosine, and the tautomer
of guanine binds with thymine.
Okay, so these are the structures,
but what we're really interested in in biology has more to do
with what happens to the DNA: typical
and atypical base pairings.
You guys ready?
We're going to look at a very simple strand.
This is ultimately supposed to code for the amino acid lysine.
We're going to replicate it twice.
We're going to have a tautomeric shift,
and we're going to see what happens.
You guys ready?
So here we have our first replication.
So we've got some separation here, and this adenine is going
to undergo a tautomeric shift.
I's going to switch to the imino form.
And so instead of a thymine being bound to it,
it's going to bind a cytosine.
Okay, ready?
So here are all the other bases coming
in like they're supposed to, and boom,
there's that C. That's bizarre.
Okay, let's go ahead and put the backbone in there.
It looks a little bit better.
Okay, now what's going to happen?
We're going to replicate again, and the thing to notice is
that adenine is going to revert back to the amino form.
That's the more stable form.
That's the form it's in most of the time,
but this cytosine, that stays.
It has changed -- that's the mutation --
because of the previous tautomeric shift of its partner.
Okay, let's go ahead and fill in the rest,
and now you notice we've got one mutant copy.
The rest are all wild-type or normal.
We're going to go ahead and transcribe those,
and again you're gonna see there is one change when we translate.
Instead of lysine, because of that tautomeric shift,
we get arginine instead.
Okay, so just to be super clear here --
you can see white on tautomeric shifts are a little tricky,
right?
It's not a mutation in and of itself.
It's just a change from usually a common form
to a more rare form, as we saw here from the amino form
to the imino form in the case of adenine.
The tautomeric shift in adenine produced a mutation
in the complimentary strand, and that is the mutation
which is going to cause, in this case, a change in the amino acid
from what should have been lysine to arginine.
I hope we made some sense out of those tautomeric shifts.
Now, one more question:
Is it going to matter in the final protein?
And to get at that, I'm going to recommend this video:
Amino Acids and Protein Structure.
That'll take you there.
As always, I hope that was helpful.
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