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OK. So today we're going to
spend a little bit of time on some

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elementary chemistry just to develop
our language that we use with one

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another. And so when I say hydrogen
bond, you don't stare blankly at me

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and scratch your heads. Many
of you have had this already.

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For many of you this is a
review, but it's a useful review.

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We believe here at MIT of teaching
things two or three times often,

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the same subject matter, but at
increasing levels of sophistication.

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So I do this without apology.
Our first issue here is how are

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atoms and molecules held together?
And the most familiar way by which

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atoms and molecules are
held together is, of course,

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the covalent bonds. And covalent
bonds have an energy of roughly 80

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kilocalories per mole. And
that's a rather strong energy to

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hold together two atoms because
the energy, the thermal energy,

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that is the energy at, let's
say, body temperature is about 0.6

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kilocalories per mole. And,
therefore, if you had a bond,

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if there was something holding
things together that was in this

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range or two or three or four
times higher then the simple thermal

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energy at room temperature or at
body temperature would be sufficient

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to break apart such a bond.
But, in fact, this energy,

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the energy of a covalent bond is
so much higher that it's highly

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unlikely that thermal energy is
going to break apart a preexisting

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covalent bond. And I was
just reading yesterday

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about how people were analyzing
the mitochondrial DNA from some

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Neanderthal bones which were dug
up. The last Neanderthal lived around

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30,000 years ago, our
recently demised cousins.

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And they were analyzing the DNA
sequences. And they got out of

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those analyses stretches of DNA
that were 200, 300 nucleotides long.

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And that really is stunning
testimonial to the fact that under

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very difficult conditions,
nonetheless, complex biological

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molecules are able to survive
over astounding periods of time,

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indeed those that are held together
by the covalent bonds like this.

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Of course, you remember the film
Jurassic Park where they used PCR

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reaction to resurrect the DNA
of dinosaurs. That's a bit of a

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fantasy since dinosaurs left us, I
guess, about 150 million years ago,

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something like that.
There's a big difference,

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obviously, between 300,000
and 150 million year ago.

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Now, the fact is if you look at
the way that molecules are actually

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hooked up, for instance, let's
look at a water molecule here.

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Ideally there should be
no charge on this molecule.

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And, in fact, there is no net
charge. But the truth of the matter

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is, if one wants to get frank,
that oxygen molecules, and we always

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are here, that oxygen molecules
have a greater affinity for electrons

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than do hydrogen atoms, i.e.,
they are electronegative.

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And, therefore, what this means is
that the swarms of electrons that

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are holding all this together at the
orbitals are drawn more closely to

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the oxygen and the hydrogen atoms,
i.e., the protons are relatively

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willing to give up their electrons.
And what this means is that there's

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an unequal distribution. And,
as a consequence, there is a

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fraction of a negative charge here
at this end of the molecule and

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there are fractions of positive
charges here because it's not as if

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they've totally given up the
electrons, but the electrons are

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shifted more in this direction.
And this molecule is therefore

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called a polar molecule by virtue of
the fact that here it has a positive

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pole and here it has a negative pole.
There are other pairs of molecules

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which are relatively
equally electronegative.

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For example, here, if we
have a carbon and a hydrogen,

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these two atoms are roughly equally
matched in terms of their ability to

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pull electrons away,
one from the other. And,

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as a consequence, there is
no net shifting of charge.

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And keep in mind that this delta I
show here is only a fraction of an

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electronic charge. It's
not the entire electronic

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charge moved over. But this
has important consequences

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for the entire biochemistry that
we're about to get into both today

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and on Monday. Important
because polar molecules,

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such as water like this, are able
to dissolve certain compounds.

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And nonpolar molecules, which have
large arrays of these kinds of bonds

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or carbon-carbon bonds, these
are relatively insoluble in

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water, and that has important
consequences for the organization of

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biological membranes. We might
have a carbonyl bond here,

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that is a C going to an O via
a double bond. And here we have,

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once again, a situation where the
oxygen is far more avid in terms of

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its willingness and interest in
pulling electrons toward itself.

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And, therefore, the carbon gives up
a little bit of the electron cloud

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and it becomes slightly electropositive.

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Whereas, the oxygen atom
becomes slightly electronegative.

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Now, the fact of the matter is that
there are also other bonds that are

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noncovalent and are much
less energetic. For example,

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let's talk for a moment
about a hydrogen bond.

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And it's perhaps easiest to
demonstrate a hydrogen bond by

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looking at the structure of two
neighboring water molecules in a

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solution of water of all things.
And, the fact of the matter is,

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let's say we draw one water molecule
down here and one water molecule

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down here. What will happen is that
this oxygen atom over here by virtue

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of its electronegativity will have
a certain affinity for pulling this

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hydrogen atom toward itself. And,
in fact, what actually happens

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in real life, whatever that
is at the molecular level,

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is that this hydrogen atom may
actually be bouncing back and forth

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between these two oxygens. It
may be rapidly an interchange

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between them. This interchange
causes a strong association between

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two neighboring water molecules.
And, indeed, represents the reason

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why water does not vaporize at
room temperature because the water

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molecules have a strong affinity
or an avidity for one another.

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And, therefore, just to take some
illustrations out of the book,

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this is the way it's
illustrated in the book.

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Probably good to have a screen down.
And here you can see the way that

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water molecules are actually
arrayed in water. This is the lower

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illustration here. Just
to indicate to you that the

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hydrogen atoms are not really the
possession, the ownership of one

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molecule of water. They're
just constantly being

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exchanged back and forth. And
this back and forth exchange,

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this sharing of a hydrogen atom
is what enables a hydrogen bond of

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roughly 5 kilocalories of energy
per mole to hold things together.

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5 kilocalories is not much.
It's only one order of magnitude

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above 0.6 rather than being
two orders of magnitude.

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And, therefore, if one raises the
temperature to the level of boiling,

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if the temperature is high enough,
the thermal energy is high enough to

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rip apart these
kinds of associations.

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Now, if we were to go back here to
look at this carbonyl atom we would

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find the following sort of situation.
Here we have this unequal sharing

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of electropositive and
electronegative bonds.

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Let's put an acidic group like
this. This is a carboxylic acid right

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here. Here we see a carbon
bond to a hydroxyl here via

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this oxygen atom.
Here, once again,

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we have an electronegative atom.
And, in fact, if we talk about an

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ionized acid, normally in the
absence of ionization there would be

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a net zero charge right here.
But at neutral pH it may well be

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the case that the association,
for various reasons, between this

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oxygen and this hydrogen will allow
the hydrogen, or rather the proton,

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the nucleus of the hydrogen
atom to just wander away.

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And, therefore, we can imagine
there could be a net negative

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charge here. A whole,
this has one full electron,

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electronegative charge here,
the charge of one electron,

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and this proton will have ionized,
will have left the carboxylic group

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in which it originated, and
now we have an ionized acid

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group. Either before or
even after this ionization,

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there is a strong affinity of the
carboxyl group with the water around

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it because let's look at what
happened before the ionization

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occurred. This carbon
here is strong and

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electronegative. And,
therefore, it will participate

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in hydrogen bonding to
the water solvent here, i.

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., this proton will be shared a
bit between the oxygen of the water

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molecule and the oxygen right here.
Similarly, here this oxygen will be

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slightly electronegative for
the reasons I've just described.

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And here, once again, there may be
some weak hydrogen bonding going on.

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Although, not as effective as over
here where we have a double-bond

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where we have a lot of concentration
of a cloud of electrons pulled

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towards the oxygen atom. And
this begins to give us clues as

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to why certain molecules are soluble
in water and others are insoluble.

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For example, if we look
at aliphatic compounds.

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Let's look at a compound
that's structured like this.

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I guess most people
would call this

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pentane. And we can call it
that, too. And this has no

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electronegativity or positivity by
virtue of the equal affinities of

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these two kinds of atoms, that
is the hydrogen and the carbons

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for electrons. And
as a consequence,

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this will not be able to form any
hydrogen bonds with a solvent around

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it if the solvent
happens to be water.

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So there's not good bonding here.
And this will, in fact, also if one

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puts this in a solution of water,
this will cause all the water

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molecules to line up in a certain
way, almost a quasi-crystal around

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the aliphatic molecule.
They'll be ordered in a certain

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layer around the aliphatic molecule
without being able to form any

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strong hydrogen bonds with them.
And this ordering represents a loss

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of chaos, a loss of entropy.
Entropy is chaos. It's disorder.

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It's what happens, let's say, at
10:55 when we all leave the room,

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all of a sudden order
becomes chaotic. And here,

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before this lining up occurred,
the water molecules were chaotically

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arrayed throughout the solvent.
After this lining up occurred there

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was a loss of entropy,
there was a loss of chaos.

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And thermodynamics tells us that
generally the ordering of molecules

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is disfavored. And
consequently we now have two

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reasons why this molecule doesn't
like to be in the midst of water.

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First of all, it's unable to form
hydrogen bonds with the solvent.

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And second of all there is
a decrease in the entropy,

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in the chaos that occurs when this
molecule directly confronts water.

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And because of those two reasons it
turns out that this molecule doesn't

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like to be in water.
The aliphatic molecule,

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as one would call this in organic
chemistry, doesn't like to be in

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water. And a dislike of water is
often called its hydrophobicity,

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or we often call it hydro,
might as well spell it right,

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hydrophobic, i.e., it
really hates to be in water.

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In fact, class, there's
a second meaning for

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hydrophobia, or hydrophobic
has a second meaning.

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Every five years I ask a class
to see who knows what the second

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meaning of hydrophobia is.
This is really obscure. Sorry?

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Rabies, right. The TAs
aren't allowed to answer that.

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If somebody has rabies, at one
stage of rabies, almost near

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the terminal stage, the
individual becomes hydrophobic

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because he or she doesn't like to
drink water, for reasons that are

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obscure at least to
me. Now, conversely,

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molecules that have carboxyl group
on it would be called hydrophilic.

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And, as we'll see over this
lecture and the next one,

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these hydrophobic and hydrophilic
tendencies tend to have great

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affects on the overall
behavior of molecules. Let's,

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for example, imagine a situation
where we have a long aliphatic tail

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like this. In fact, these
tails can go on in certain

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aliphatic compounds. They
can go on for 20 or even 30

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carbons. And at the end of this,
let's just put arbitrarily a

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carboxyl group. And
let's say we ionized it.

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So here's an acidic group that's
ionized. It's shed its proton.

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It's actually acquired a negative
charge. And now we have something,

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this molecule is a bit schizoid.
Because on one end of it,

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it loves to be in water, the other
end of it hates to be in water.

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And this has strong affects.
It's sometimes called amphipathic,

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but we don't need to
worry about that word. And,

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therefore, this carboxyl
head loves to stick its head,

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to immerse its head in water.
And these things, the aliphatic

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portion hates to be in water.
Now, as a consequence of these

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rather conflicted feelings that
these molecules have about water,

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we can ask the question what
happens when we put such molecules

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actually into water? And
what we see here is the

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following. That if we were
to construct, for example,

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a molecule of the sort that has here,
in this case we're talking about a

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molecule that has two hydrophobic
tails. We'll get into its detailed

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structure shortly, but just
imagine for a moment two

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long hydrophobic tails out here
ended with a hydrophilic head.

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And under such situations, if
we put thousands of these or

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millions of these molecules
into a solution of water,

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what we will then see is, no
pointer? All right. Pointer?

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All right. What we will then see
is that the hydrophilic head groups,

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which are here depicted in red,
will point their way outwards,

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they will want to stick
their heads in water.

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And conversely the hydrophobic tails
fleeing from the water will actually

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associate one with the other.
And so you have a structure that's

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called, in this case, an a
micelle where you form this

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little globular sphere where the
lipid tails are tucked inside.

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And, therefore, are actually being
shielded from any direct exposure to

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water. This structure down here,
the lipid bilayer, is actually, as

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we will discuss in greater detail
shortly, the overall topology of the

220
00:16:31,000 --> 00:16:36,000
way most biological
membranes are organized.

221
00:16:36,000 --> 00:16:40,000
In fact, virtually all of them.
Why is that? Because biological

222
00:16:40,000 --> 00:16:45,000
membranes separate two
hydrophilic or two aqueous spaces.

223
00:16:45,000 --> 00:16:50,000
Thank you, sir. A gentleman you
are. So here is an aqueous space

224
00:16:50,000 --> 00:16:55,000
and here is an aqueous space. And
as we see the hydrophilic heads

225
00:16:55,000 --> 00:17:00,000
are immersed or sticking their
heads into the hydrophilic space.

226
00:17:00,000 --> 00:17:04,000
This is called a lipid bilayer.
And, obviously, it's highly

227
00:17:04,000 --> 00:17:08,000
effective for separately
these two aqueous compartments.

228
00:17:08,000 --> 00:17:12,000
In eukaryotic cells, as I mentioned
last time, there is an enormous

229
00:17:12,000 --> 00:17:16,000
premium placed on separating
and segregating different aqueous

230
00:17:16,000 --> 00:17:20,000
compartments which is invariably
achieved through the device of

231
00:17:20,000 --> 00:17:24,000
constructing these lipid bilayers.
Here's a vesicle. A vesicle is

232
00:17:24,000 --> 00:17:28,000
more complicated than a micelle.
Because if you look at the membrane

233
00:17:28,000 --> 00:17:32,000
lining the vesicle, you
see it's actually a lipid

234
00:17:32,000 --> 00:17:36,000
bilayer, but one that in
3-dimensional space is actually a

235
00:17:36,000 --> 00:17:40,000
sphere. And in the case of this
vesicle, we can well imagine that on

236
00:17:40,000 --> 00:17:43,000
the inside of the vesicle
water is kept, can be stored,

237
00:17:43,000 --> 00:17:47,000
and on the outside of the
vesicle water can be stored.

238
00:17:47,000 --> 00:17:51,000
And many of the membranes that we
see within the cytoplasms themselves

239
00:17:51,000 --> 00:17:55,000
are actually constructed
on this kind of design.

240
00:17:55,000 --> 00:17:58,000
So when we draw, for example,
in this case the Golgi

241
00:17:58,000 --> 00:18:02,000
apparatus, which I mentioned to
you in passing last time we met,

242
00:18:02,000 --> 00:18:05,000
each one of these membranes here,
it's obviously drawn as a double

243
00:18:05,000 --> 00:18:09,000
line, but whenever you
see a membrane indicated,

244
00:18:09,000 --> 00:18:13,000
implicit in that drawing is the fact
that each one of these membranes is

245
00:18:13,000 --> 00:18:16,000
actually a bilayer. There
are never any monolayers of

246
00:18:16,000 --> 00:18:20,000
lipids in living cells. Each
one of these vesicles you see

247
00:18:20,000 --> 00:18:24,000
here is actually a lipid bilayer
with an aqueous inside and,

248
00:18:24,000 --> 00:18:28,000
once again, aqueous on the outside.
Again, much of the thermodynamic

249
00:18:28,000 --> 00:18:34,000
stability that allows these vesicles
to remain intact rather than just

250
00:18:34,000 --> 00:18:39,000
diffuse apart is created by these
hydrophilic and hydrophobic forces

251
00:18:39,000 --> 00:18:45,000
which tie such molecules
together or will rip them apart.

252
00:18:45,000 --> 00:18:51,000
Now, in truth there are yet other
kinds of forces that govern the

253
00:18:51,000 --> 00:18:56,000
affinity of molecules to one
another. For example, let's imagine a

254
00:18:56,000 --> 00:19:02,000
situation where we have an ionized
acid group of the sort we just

255
00:19:02,000 --> 00:19:07,000
talked about before.
Now, by the way,

256
00:19:07,000 --> 00:19:11,000
here, let's say I'll draw the
negative charge on one of these two

257
00:19:11,000 --> 00:19:15,000
oxygens, if you can see that. But
the truth is that the electrons

258
00:19:15,000 --> 00:19:19,000
are swarming back and forth, and
so the negative charge is shared

259
00:19:19,000 --> 00:19:23,000
equally, the negative one electron
charge is shared equally between

260
00:19:23,000 --> 00:19:27,000
these two oxygen atoms. And
this is obviously an area of

261
00:19:27,000 --> 00:19:32,000
great electronegativity.
Independent of that,

262
00:19:32,000 --> 00:19:36,000
let's imagine up here we have a
basic group, let's say an amine

263
00:19:36,000 --> 00:19:40,000
group over here. And,
the fact of the matter is,

264
00:19:40,000 --> 00:19:44,000
amine groups, NH2 groups,
that's what an amine is,

265
00:19:44,000 --> 00:19:48,000
here's an amine group.
This is a carboxylic group.

266
00:19:48,000 --> 00:19:52,000
And the amine group, which is
used very often in biochemistry,

267
00:19:52,000 --> 00:19:56,000
actually has an affinity. It has
an unpaired set of electrons on the

268
00:19:56,000 --> 00:20:00,000
nitrogen, and so it likes
to attract protons to it,

269
00:20:00,000 --> 00:20:04,000
which makes it, causes
it to be called basic.

270
00:20:04,000 --> 00:20:08,000
And this attraction, the
scavenging of protons,

271
00:20:08,000 --> 00:20:12,000
perhaps from the water, will
obviously give this whole group here

272
00:20:12,000 --> 00:20:16,000
a net positive charge, a charge
equal to the charge of one

273
00:20:16,000 --> 00:20:20,000
proton. Here, once again,
we can imagine this is

274
00:20:20,000 --> 00:20:24,000
hydrophilic because this charge
group can once again also associate

275
00:20:24,000 --> 00:20:29,000
quite intimately
with aqueous solvent.

276
00:20:29,000 --> 00:20:33,000
Now, independent of any other
forces that might exist here,

277
00:20:33,000 --> 00:20:37,000
indeed one could imagine situations
where there is a sharing of a proton.

278
00:20:37,000 --> 00:20:41,000
And, therefore, a hydrogen
bond formed between these

279
00:20:41,000 --> 00:20:45,000
two. Independent of that is the
simple electrostatic interaction of

280
00:20:45,000 --> 00:20:50,000
these two groups. That is
the mutual attraction of

281
00:20:50,000 --> 00:20:54,000
positive and negative groups,
one to the other. And the

282
00:20:54,000 --> 00:20:58,000
electrostatic interactions, you
cannot quantify exactly how many

283
00:20:58,000 --> 00:21:02,000
kilocalories a mole there is because
the energetic value in electrostatic

284
00:21:02,000 --> 00:21:06,000
interaction is equal to one over
r squared where r is the distance

285
00:21:06,000 --> 00:21:11,000
between these two charged groups.
And obviously the further apart you

286
00:21:11,000 --> 00:21:15,000
get the weaker the attraction with
one another. There are also what

287
00:21:15,000 --> 00:21:19,000
are called van der Walls
interactions. There are largely of

288
00:21:19,000 --> 00:21:23,000
interest to a very small
community of biochemists.

289
00:21:23,000 --> 00:21:27,000
You probably will never, you
may never hear this term again

290
00:21:27,000 --> 00:21:32,000
in your life. And van der
Waals interactions come

291
00:21:32,000 --> 00:21:36,000
from the fact that if we
were to have, for example,

292
00:21:36,000 --> 00:21:40,000
two molecules over here which are
not normally charged in any way,

293
00:21:40,000 --> 00:21:44,000
let's just talk about two aliphatic
chains again. And I won't put in

294
00:21:44,000 --> 00:21:49,000
all the protons and everything,
but just imagine a situation like

295
00:21:49,000 --> 00:21:53,000
this. What will happen is that
because of the fluctuations of

296
00:21:53,000 --> 00:21:57,000
electrons, because the electrons are
swimming around here all the time,

297
00:21:57,000 --> 00:22:02,000
moving from one area to the next
they're never equally distributed

298
00:22:02,000 --> 00:22:06,000
homogenously over a long period of
time, there will be brief instance

299
00:22:06,000 --> 00:22:10,000
in time, microseconds or even
nanoseconds when there happens to be

300
00:22:10,000 --> 00:22:15,000
more electrons over
here than right here.

301
00:22:15,000 --> 00:22:19,000
Just by chance. And
this area of unequal

302
00:22:19,000 --> 00:22:23,000
distribution of electrons will in
turn induce the opposite kind of

303
00:22:23,000 --> 00:22:27,000
electron shift in a
neighboring molecule down here.

304
00:22:27,000 --> 00:22:31,000
Obviously, depending on
the distance between them.

305
00:22:31,000 --> 00:22:34,000
But the negative here will
repel electrons down here.

306
00:22:34,000 --> 00:22:38,000
The positive here will
attract electrons down here.

307
00:22:38,000 --> 00:22:42,000
And so you will have these two
quasi-polar arrangements here and

308
00:22:42,000 --> 00:22:46,000
here, very ephemeral, that
is lasting for a very short

309
00:22:46,000 --> 00:22:50,000
transient period of time.
But, nonetheless, sufficient to

310
00:22:50,000 --> 00:22:54,000
give a very weak interaction
between these two molecules which may

311
00:22:54,000 --> 00:22:58,000
persist only for a microsecond
and then be dissipated because the

312
00:22:58,000 --> 00:23:02,000
charges then
redistributed once again.

313
00:23:02,000 --> 00:23:06,000
And, as a consequence of that, one
has very weak interactions which,

314
00:23:06,000 --> 00:23:11,000
in the great scheme of things,
play only a very minor role in the

315
00:23:11,000 --> 00:23:16,000
overall energy which holds
molecules together. Now,

316
00:23:16,000 --> 00:23:21,000
with that background in mind,
let's begin to elaborate on it,

317
00:23:21,000 --> 00:23:25,000
on how we can make molecules that
have interesting properties that

318
00:23:25,000 --> 00:23:30,000
enable them, among other things,
to participate in the construction

319
00:23:30,000 --> 00:23:35,000
of lipid bilayers, which
will be the first object of

320
00:23:35,000 --> 00:23:40,000
our attentions today in
terms of actual biochemistry.

321
00:23:40,000 --> 00:23:44,000
So here's a fatty acid.
We see that up here. I,

322
00:23:44,000 --> 00:23:48,000
in effect, drew you the structure
of a fatty acid up here already once

323
00:23:48,000 --> 00:23:53,000
before. And what we can see
is through a linkage known as

324
00:23:53,000 --> 00:23:57,000
esterification we can create
this molecule. So what do I

325
00:23:57,000 --> 00:24:02,000
mean by esterification? Well,
in this case we're talking

326
00:24:02,000 --> 00:24:07,000
about a situation here where we have
a carbon atom over here like this

327
00:24:07,000 --> 00:24:12,000
with a hydroxyl group. You
see it over here. And what

328
00:24:12,000 --> 00:24:17,000
we're doing is we're dehydrating
this, we're pulling out one net

329
00:24:17,000 --> 00:24:22,000
molecule of water. And
each time we do that,

330
00:24:22,000 --> 00:24:27,000
on three separate occasions,
what we end up doing is to create

331
00:24:27,000 --> 00:24:32,000
instead of this is to create a
covalent bond between these two.

332
00:24:32,000 --> 00:24:36,000
And so the end product
of dehydrating this,

333
00:24:36,000 --> 00:24:40,000
pulling out one net molecule of
water is that we end up with a

334
00:24:40,000 --> 00:24:48,000
structure that
looks like this.

335
00:24:48,000 --> 00:24:53,000
And you see that happening on at
least three different occasions,

336
00:24:53,000 --> 00:24:58,000
here, here and here. Well, actually,
I should put a carbon over here.

337
00:24:58,000 --> 00:25:02,000
So here we have
three esterifications.

338
00:25:02,000 --> 00:25:07,000
The hydroxyl group in each case is
reacting with a carboxyl group here

339
00:25:07,000 --> 00:25:11,000
pulling out one water, and
each case creating what's called

340
00:25:11,000 --> 00:25:16,000
triacylglyercol or triglyceride.
Triglyceride refers to the fact

341
00:25:16,000 --> 00:25:21,000
that we started here with a glycerol
and we have now esterified it.

342
00:25:21,000 --> 00:25:25,000
Now, in fact, there are
two directions here in this

343
00:25:25,000 --> 00:25:30,000
kind of reaction.
Esterification is the kind of

344
00:25:30,000 --> 00:25:34,000
linkage that we just showed here.
And the truth is that vast numbers

345
00:25:34,000 --> 00:25:38,000
of biochemical linkages are made
by esterification reactions and

346
00:25:38,000 --> 00:25:43,000
reversed by reactions that
are called simply hydrolysis.

347
00:25:43,000 --> 00:25:47,000
And, in this case, what we're
referring to is the fact that if one

348
00:25:47,000 --> 00:25:51,000
were to reintroduce a water molecule
into each of these three linkages,

349
00:25:51,000 --> 00:25:56,000
one, two and three, we would break
the bond and cause this entire

350
00:25:56,000 --> 00:26:00,000
structure to revert to the
two precursors that existed or

351
00:26:00,000 --> 00:26:05,000
preexisted prior to these
three esterification reactions.

352
00:26:05,000 --> 00:26:10,000
And time and again you'll
see, over the next weeks, that

353
00:26:10,000 --> 00:26:16,000
esterification reactions are
important for constructing different

354
00:26:16,000 --> 00:26:22,000
kinds of molecules. Now,
the fact of the matter is we

355
00:26:22,000 --> 00:26:28,000
can do other kinds of modifications
of a glycerol like this.

356
00:26:28,000 --> 00:26:32,000
Here what we've done, instead
of adding a third fatty acid,

357
00:26:32,000 --> 00:26:36,000
note what was done here. Here
through an esterification,

358
00:26:36,000 --> 00:26:40,000
let's look up at this one here,
instead of adding a third fatty acid,

359
00:26:40,000 --> 00:26:44,000
we've saved, we've reserved one of
the three groups of the glycerol.

360
00:26:44,000 --> 00:26:48,000
Here's what we saw just before.
We've saved one of the three groups

361
00:26:48,000 --> 00:26:52,000
of the glycerol and put on instead
this highly hydrophilic phosphate

362
00:26:52,000 --> 00:26:56,000
group, once again through
a dehydration reaction, an

363
00:26:56,000 --> 00:27:00,000
esterification reaction. And
now what we've done is add

364
00:27:00,000 --> 00:27:04,000
insult to injury because in the
absence of this phosphate it would

365
00:27:04,000 --> 00:27:07,000
have a hydroxyl here which is
mildly hydrophilic. But now look how

366
00:27:07,000 --> 00:27:11,000
strongly charged this is.
Here are two negative charges,

367
00:27:11,000 --> 00:27:14,000
one electron each. And this is
already a bit electronegative.

368
00:27:14,000 --> 00:27:18,000
So here we have an extremely
potent hydrophilic entity.

369
00:27:18,000 --> 00:27:21,000
And here the degree of
schizophrenia between one end of the

370
00:27:21,000 --> 00:27:25,000
molecule and the other is
greatly exaggerated. Here,

371
00:27:25,000 --> 00:27:29,000
in fact, this is
extremely hydrophilic.

372
00:27:29,000 --> 00:27:33,000
And, as a consequence of that,
this really likes to stick its head

373
00:27:33,000 --> 00:27:37,000
inside water. And when we therefore
talk about, we draw the images of

374
00:27:37,000 --> 00:27:41,000
different kinds of membranes,
like this I showed you before the

375
00:27:41,000 --> 00:27:46,000
two tails. Here you saw the two
tails I drew before in that diagram.

376
00:27:46,000 --> 00:27:50,000
Here's what we can imagine they
actually look like in more real

377
00:27:50,000 --> 00:27:54,000
molecular terms. And the
hydrophilic heads sticking

378
00:27:54,000 --> 00:27:58,000
in the water, this is just
repeating what we saw before,

379
00:27:58,000 --> 00:28:03,000
become even more hydrophilic if
we look at a molecule like this.

380
00:28:03,000 --> 00:28:07,000
Let's look at this thing here.
Here's a very long hydrophobic tail.

381
00:28:07,000 --> 00:28:11,000
Here are the two glycerols once
again. Here is the phosphate.

382
00:28:11,000 --> 00:28:15,000
And keep in mind that phosphate
obviously has these extra oxygens.

383
00:28:15,000 --> 00:28:19,000
Phosphate can react with
more than just one partner,

384
00:28:19,000 --> 00:28:23,000
the glycerol down here. In
this case we've added this group

385
00:28:23,000 --> 00:28:27,000
up here. And this group up here
is, once again, this happens to be a

386
00:28:27,000 --> 00:28:31,000
serine which is an amino acid,
this also happens to be quite

387
00:28:31,000 --> 00:28:35,000
hydrophilic. Here's
our old friend the basic

388
00:28:35,000 --> 00:28:39,000
amino group. Here's the carboxyl
group. This is a bit hydrophobic,

389
00:28:39,000 --> 00:28:43,000
CH2. And then we once again
have the hydrophilic head here.

390
00:28:43,000 --> 00:28:47,000
And, therefore, we imagine,
if we look at what's called a

391
00:28:47,000 --> 00:28:50,000
space-filling model, and a
space-filling model really is

392
00:28:50,000 --> 00:28:54,000
intended to show us what one
imagines if one had this vision,

393
00:28:54,000 --> 00:28:58,000
which we don't have, how much space
each of these atoms would actually

394
00:28:58,000 --> 00:29:02,000
take up if one were
able to see them.

395
00:29:02,000 --> 00:29:07,000
And here we see this space filling
model. This lipid molecule here is

396
00:29:07,000 --> 00:29:12,000
actually slightly kinked with its
hydrophilic head tucked into the

397
00:29:12,000 --> 00:29:18,000
water space. And so here's actually
the way that many biological

398
00:29:18,000 --> 00:29:23,000
membranes look in terms of the
way that they are constructed.

399
00:29:23,000 --> 00:29:28,000
Now, the fact of the matter is this
also affords the cell the ability to

400
00:29:28,000 --> 00:29:34,000
segregate contents on one or the
other side of whatever lipid bilayer

401
00:29:34,000 --> 00:29:39,000
it happens to have constructed.
And here we can see about the

402
00:29:39,000 --> 00:29:44,000
semi-permeability, how
permeable these membranes are to

403
00:29:44,000 --> 00:29:49,000
different kinds of molecules.
Permeability obviously refers to

404
00:29:49,000 --> 00:29:54,000
the ability of this membrane to
obstruct or to allow the migration

405
00:29:54,000 --> 00:30:00,000
of molecules from
one side to the other.

406
00:30:00,000 --> 00:30:03,000
Ions, and these ions we see
right here are obviously highly

407
00:30:03,000 --> 00:30:07,000
hydrophilic by virtue of
their charge. That's explains,

408
00:30:07,000 --> 00:30:11,000
in fact, why, for example,
table salt goes so readily into

409
00:30:11,000 --> 00:30:15,000
solution, because it readily
ionizes into sodium, NA and CL,

410
00:30:15,000 --> 00:30:18,000
which then are avidly taken
up by the water molecules.

411
00:30:18,000 --> 00:30:22,000
So these are highly hydrophilic
ions. And the questions is,

412
00:30:22,000 --> 00:30:26,000
can they go from one side
of the membrane to the other?

413
00:30:26,000 --> 00:30:30,000
And the answer is absolutely
not or highly improbably. Why?

414
00:30:30,000 --> 00:30:33,000
Because these are so highly
hydrophilic, the water molecules

415
00:30:33,000 --> 00:30:37,000
love to gather around them and form
hydrogen bonds and electrostatic

416
00:30:37,000 --> 00:30:40,000
bonds with them. And if
one of these ions ventures

417
00:30:40,000 --> 00:30:44,000
over here, it's going from an area
where it's warmly embraced by the

418
00:30:44,000 --> 00:30:47,000
solvent molecules to an area where
these molecules intensely dislike

419
00:30:47,000 --> 00:30:51,000
these ions. And, therefore,
thermodynamically the

420
00:30:51,000 --> 00:30:55,000
entrance of any one of
these ions into the membrane,

421
00:30:55,000 --> 00:30:58,000
into the hydrophobic portion of
the membrane is highly disfavored,

422
00:30:58,000 --> 00:31:02,000
which makes the membrane essentially,
for all practical purposes,

423
00:31:02,000 --> 00:31:05,000
impermeable. The same
can be said of glucose

424
00:31:05,000 --> 00:31:09,000
which happens to be a carbohydrate.
We'll talk about it shortly. But

425
00:31:09,000 --> 00:31:12,000
it's also nicely hydrophilic.
It also can go in water. In fact,

426
00:31:12,000 --> 00:31:15,000
it can go through. And
it's actually the case,

427
00:31:15,000 --> 00:31:19,000
to my knowledge, that one doesn't
really understand to this day why

428
00:31:19,000 --> 00:31:22,000
lipid bilayers are
reasonably permeable to water.

429
00:31:22,000 --> 00:31:26,000
You would say, well, water
shouldn't be able to go

430
00:31:26,000 --> 00:31:29,000
through. It clearly
doesn't have to have a

431
00:31:29,000 --> 00:31:32,000
net positive or negative charge,
but the physical chemist, if you

432
00:31:32,000 --> 00:31:35,000
asked them why does water,
why is water able to go through

433
00:31:35,000 --> 00:31:38,000
lipid bilayers?
They'll say, well,

434
00:31:38,000 --> 00:31:41,000
we've been working on that and we'll
get you an answer in the next five

435
00:31:41,000 --> 00:31:44,000
or ten years. And they said that
40 years ago and 30 years ago,

436
00:31:44,000 --> 00:31:47,000
and they're still saying it. And
we don't really understand why

437
00:31:47,000 --> 00:31:50,000
water goes through, which
is an embarrassment because

438
00:31:50,000 --> 00:31:53,000
here's one of the fundamental
biochemical properties of living

439
00:31:53,000 --> 00:31:56,000
matter that is poorly understood.
Gases can go right through.

440
00:31:56,000 --> 00:32:00,000
And amino acids, ATP,
glucose 6 phosphate,

441
00:32:00,000 --> 00:32:05,000
highly hydrophilic, can
also not go through. Now,

442
00:32:05,000 --> 00:32:09,000
the advantage of this is that a cell
can accumulate large concentrations

443
00:32:09,000 --> 00:32:14,000
of these molecules either on the
inside or it can pump them to the

444
00:32:14,000 --> 00:32:19,000
outside. In other words, it can
create great gradients in the

445
00:32:19,000 --> 00:32:23,000
concentrations of different
kinds of ions. For example,

446
00:32:23,000 --> 00:32:28,000
in many cells, the concentration
of calcium, CA++ is a thousand times

447
00:32:28,000 --> 00:32:33,000
higher on the outside of the cell
than on the inside of the cell which

448
00:32:33,000 --> 00:32:38,000
is a testimonial to how impermeable
these lipid bilayer membranes are.

449
00:32:38,000 --> 00:32:41,000
The fact of the matter is I'm
fudging a little bit here because in

450
00:32:41,000 --> 00:32:45,000
the lipid bilayers of the
plasma membrane of the cell,

451
00:32:45,000 --> 00:32:49,000
the outer membrane of the cell that
we talked about in passing last time,

452
00:32:49,000 --> 00:32:53,000
there are ion pumps which are
constantly working away pumping ions

453
00:32:53,000 --> 00:32:57,000
from one side to the other overcomes
the little bit of leakage which may

454
00:32:57,000 --> 00:33:01,000
have occurred if a calcium ion
happens to have snuck through in one

455
00:33:01,000 --> 00:33:05,000
direction or the other. And
we end up expending a lot of

456
00:33:05,000 --> 00:33:10,000
energy to keep these ion gradients
in appropriate concentrations on the

457
00:33:10,000 --> 00:33:15,000
outside and the inside. In
fact, virtually all the energy

458
00:33:15,000 --> 00:33:20,000
that is expended in our brain,
almost all of it is expended to

459
00:33:20,000 --> 00:33:25,000
power the ion pumps which are
constantly insuring that the

460
00:33:25,000 --> 00:33:30,000
concentrations of certain ions
on the outside and the inside of

461
00:33:30,000 --> 00:33:36,000
neurons are kept at their
proper respective levels.

462
00:33:36,000 --> 00:33:40,000
It could therefore be that actually
more than half of our metabolic

463
00:33:40,000 --> 00:33:44,000
burden every day is expended just
keeping the ions segregated on the

464
00:33:44,000 --> 00:33:48,000
outside and inside of cells.
For example, potassium is at high

465
00:33:48,000 --> 00:33:52,000
levels inside cells, sodium
is at high levels outside

466
00:33:52,000 --> 00:33:56,000
cells, just to site some
arbitrary examples. There are also,

467
00:33:56,000 --> 00:34:00,000
by the way, as I mentioned
last time, channels.

468
00:34:00,000 --> 00:34:04,000
And channels are actually just
little doughnut shaped objects which

469
00:34:04,000 --> 00:34:08,000
are placed, inserted into lipid
bilayers in the plasma membranes and

470
00:34:08,000 --> 00:34:13,000
just allow for the passive
diffusion of an ion through them,

471
00:34:13,000 --> 00:34:17,000
through the doughnut hole enabling
an ion, so if here's the lipid

472
00:34:17,000 --> 00:34:22,000
bilayer, not showing its two things,
these kinds of doughnut shaped

473
00:34:22,000 --> 00:34:26,000
protein aggregates will allow
the passage of ions in one

474
00:34:26,000 --> 00:34:31,000
direction or another. And
here energy is not being

475
00:34:31,000 --> 00:34:35,000
expended to enable this passage.
It may just be through diffusion.

476
00:34:35,000 --> 00:34:39,000
If there's a higher concentration
of ion on side of the lipid bilayer

477
00:34:39,000 --> 00:34:43,000
and a lower one on this side, this
diffusion will allow the ion to

478
00:34:43,000 --> 00:34:47,000
migrate through the bore of the ion
channel from one side to the other.

479
00:34:47,000 --> 00:34:51,000
In fact, even though this does not
involve the expenditure of energy on

480
00:34:51,000 --> 00:34:55,000
the part of the cell, the
cell may actually use a gating

481
00:34:55,000 --> 00:35:00,000
mechanism to open or
close these channels.

482
00:35:00,000 --> 00:35:04,000
When the channels are closed
then the ions cannot move through.

483
00:35:04,000 --> 00:35:08,000
When the channels are gated open
then diffusion can take over and

484
00:35:08,000 --> 00:35:12,000
insure the transfer, the
transportation of ions from one

485
00:35:12,000 --> 00:35:17,000
side to the other.
Now, having said that,

486
00:35:17,000 --> 00:35:21,000
we can begin to look at yet
other higher level structures.

487
00:35:21,000 --> 00:35:25,000
Here, by the way, is a better
drawing than the one I provided you.

488
00:35:25,000 --> 00:35:30,000
This comes from your book
of what a vesicle looks like.

489
00:35:30,000 --> 00:35:34,000
Here's what it looks like under the
electron microscope and here's what

490
00:35:34,000 --> 00:35:39,000
it looks like when a talented rather
than hapless and hopeless artist

491
00:35:39,000 --> 00:35:44,000
like myself tries to draw it. So
let's just say that's our intro

492
00:35:44,000 --> 00:35:49,000
into lipids and membranes. And
let's move onto the next layer

493
00:35:49,000 --> 00:35:54,000
of complexity. And the
next layer of complexity in

494
00:35:54,000 --> 00:35:59,000
terms of molecules
represents carbohydrates.

495
00:35:59,000 --> 00:36:03,000
And when we talk about a
carbohydrate amongst ourselves we're

496
00:36:03,000 --> 00:36:07,000
talking about a molecule which,
roughly speaking, has one carbon

497
00:36:07,000 --> 00:36:11,000
atom for every water molecule.
And we'll shortly indulge ourselves

498
00:36:11,000 --> 00:36:15,000
in talking about all kinds of
different carbohydrate molecules.

499
00:36:15,000 --> 00:36:19,000
Here is really one of the most
important carbohydrate molecules,

500
00:36:19,000 --> 00:36:23,000
glucose. And what should
we note about glucose?

501
00:36:23,000 --> 00:36:27,000
Well, the first thing you should
see is that glucose has six carbon

502
00:36:27,000 --> 00:36:31,000
atoms. And, therefore, as
a consequence it's called a

503
00:36:31,000 --> 00:36:35,000
hexose. We're going
to talk about pentoses

504
00:36:35,000 --> 00:36:39,000
very shortly. They only have five,
to state the obvious. Glycerol,

505
00:36:39,000 --> 00:36:44,000
which we talked about before,
is also considered in one sense a

506
00:36:44,000 --> 00:36:48,000
carbohydrate, but it's been
called by some people a triose.

507
00:36:48,000 --> 00:36:53,000
It only has three carbon atoms.
And you can imagine, therefore, in

508
00:36:53,000 --> 00:36:57,000
principal that there are certain
biochemical mechanisms which indeed

509
00:36:57,000 --> 00:37:02,000
exist which enable one to
join two glycerol molecules,

510
00:37:02,000 --> 00:37:07,000
one to the other, to create
something like a hexose, glucose.

511
00:37:07,000 --> 00:37:11,000
In fact, what we see from this
drawing, expertly drawn by yours

512
00:37:11,000 --> 00:37:16,000
truly, is that the hexose molecule
isn't really a linear molecule in

513
00:37:16,000 --> 00:37:20,000
solution. What happens is that
because of various steric and

514
00:37:20,000 --> 00:37:25,000
thermodynamic forces it likes to
cyclize. So let me just mention,

515
00:37:25,000 --> 00:37:30,000
I've just used two words
that are useful to know about.

516
00:37:30,000 --> 00:37:34,000
Steric or stereochemistry refers
to the 3-dimensional structure of a

517
00:37:34,000 --> 00:37:39,000
molecule. And, obviously,
the stereochemistry of a

518
00:37:39,000 --> 00:37:43,000
molecule is dictated by the
flexibility with which participating

519
00:37:43,000 --> 00:37:48,000
atoms can form bonds, whether
we have a trivalent atom

520
00:37:48,000 --> 00:37:52,000
like nitrogen or a tetravalent
atom like carbon or a monovalent

521
00:37:52,000 --> 00:37:57,000
like hydrogen. And
these structures,

522
00:37:57,000 --> 00:38:03,000
the stereochemistry is dictated both
by what atoms are present here and

523
00:38:03,000 --> 00:38:08,000
by thermodynamic considerations
which cause this particular hexose,

524
00:38:08,000 --> 00:38:13,000
indeed virtually all hexoses,
to cyclize. When I say cyclize,

525
00:38:13,000 --> 00:38:19,000
obviously I mean to form a circular
structure. Here we note one thing.

526
00:38:19,000 --> 00:38:24,000
You can see how the hydroxyl here
actually attacks the positively

527
00:38:24,000 --> 00:38:30,000
charged carbon here in order
to form this cyclic structure.

528
00:38:30,000 --> 00:38:36,000
You see one of the six points on
this hexagonal structure here is

529
00:38:36,000 --> 00:38:43,000
oxygen. It's not carbon at all.
So there is one oxygen and five

530
00:38:43,000 --> 00:38:49,000
carbons. And one of the carbons is
relegated, is exiled to outside of

531
00:38:49,000 --> 00:38:56,000
the circle. It's sometimes called
an extracyclic because it's sticking

532
00:38:56,000 --> 00:39:02,000
out from the actual circle. And
this is the structure in which

533
00:39:02,000 --> 00:39:06,000
glucose actually exists
inside cells. And, in fact,

534
00:39:06,000 --> 00:39:10,000
there is, in truth, two
alternative ways by which

535
00:39:10,000 --> 00:39:14,000
glucose can cyclize, whether
the oxygen attacks the

536
00:39:14,000 --> 00:39:18,000
carbon on the carbonyl
group underneath or on top.

537
00:39:18,000 --> 00:39:22,000
And you see that gives us
two alternative structures.

538
00:39:22,000 --> 00:39:26,000
What's different about them?
Well, if we think about this hexose

539
00:39:26,000 --> 00:39:30,000
as existing in a plane, or
the hexagon is in a plane

540
00:39:30,000 --> 00:39:35,000
In this case the oxygen is above the
plane and the hydrogen is below the

541
00:39:35,000 --> 00:39:40,000
plane. With equal probability you
can have these two atoms reversed

542
00:39:40,000 --> 00:39:45,000
where hydrogen is now above the
plane and hydroxyl is below the

543
00:39:45,000 --> 00:39:50,000
plane. And both of these structures,
these alternative structures can

544
00:39:50,000 --> 00:39:55,000
fairly be considered to be glucose.
Now, let's get a little bit more

545
00:39:55,000 --> 00:40:00,000
complicated. Here we have
fructose and we have galactose.

546
00:40:00,000 --> 00:40:04,000
And what we see here is, by the
way, that we have exactly the

547
00:40:04,000 --> 00:40:08,000
same number of carbon atoms and
hydrogen atoms and oxygen atoms but

548
00:40:08,000 --> 00:40:12,000
they're hooked up slightly
differently. And here now we begin

549
00:40:12,000 --> 00:40:16,000
to get very picky about the
disposition, the orientation of

550
00:40:16,000 --> 00:40:20,000
these different kinds of
hydroxyls and hydrogens.

551
00:40:20,000 --> 00:40:24,000
And note, by the way, here
that in many cases one doesn't

552
00:40:24,000 --> 00:40:28,000
even put in the H for the hydrogen.
It's just implied by the end of

553
00:40:28,000 --> 00:40:31,000
this line. And here,
if you were to look at

554
00:40:31,000 --> 00:40:35,000
this, you'll see here now we
have two extra cyclic carbons.

555
00:40:35,000 --> 00:40:38,000
Here's galactose which
is yet another hexose.

556
00:40:38,000 --> 00:40:41,000
These are all hexoses, but
their stereochemistry creates

557
00:40:41,000 --> 00:40:45,000
quite different kinds of structures.
And it turns out that this

558
00:40:45,000 --> 00:40:48,000
stereochemistry is extremely
important. These molecules function

559
00:40:48,000 --> 00:40:52,000
very differently,
one from the other.

560
00:40:52,000 --> 00:40:55,000
And, for example, to the
extent that glucose is used

561
00:40:55,000 --> 00:40:59,000
in different kinds of energy
metabolism and to the extent that

562
00:40:59,000 --> 00:41:03,000
galactose is not, there
must be certain biochemical

563
00:41:03,000 --> 00:41:07,000
mechanisms in which one has
catalysts, the catalysts that we

564
00:41:07,000 --> 00:41:11,000
call enzymes that ensure that one
can convert one of these hexoses

565
00:41:11,000 --> 00:41:14,000
through an enzyme into, let's
say a less useful one into a

566
00:41:14,000 --> 00:41:18,000
more useful one, glucose,
which can readily be burnt

567
00:41:18,000 --> 00:41:22,000
up by the energy-generating
machinery. Here we've gone yet

568
00:41:22,000 --> 00:41:26,000
another order of magnitude more
complex because we've gone from a

569
00:41:26,000 --> 00:41:30,000
monosaccharide, i.e.,
one or another hexose,

570
00:41:30,000 --> 00:41:34,000
to a disaccharide. And
here's common table sugar.

571
00:41:34,000 --> 00:41:38,000
And here you see that it's formed
once again through an esterification

572
00:41:38,000 --> 00:41:42,000
reaction, i.e. there is
a dehydration reaction

573
00:41:42,000 --> 00:41:46,000
between this hydroxyl here
and this hydroxyl here.

574
00:41:46,000 --> 00:41:50,000
And biochemists take the
orientation of these hydroxyl and

575
00:41:50,000 --> 00:41:54,000
hydrogen groups very seriously.
Now, you can say they're a bit

576
00:41:54,000 --> 00:41:58,000
obsessive. Indeed
they probably are.

577
00:41:58,000 --> 00:42:02,000
But, nonetheless, we can
admit that the specific

578
00:42:02,000 --> 00:42:07,000
orientations of all these things
dictate very importantly the

579
00:42:07,000 --> 00:42:11,000
difference between here, in
this case sucrose, and in this

580
00:42:11,000 --> 00:42:16,000
case lactose. Why is this important?
Well, this is the sugar in milk

581
00:42:16,000 --> 00:42:20,000
sugar. This is the dominant
sugar in milk sugar,

582
00:42:20,000 --> 00:42:25,000
lactose. And half the world,
as adults, cannot absorb this.

583
00:42:25,000 --> 00:42:29,000
All kinds of unpleasant things
happen when they actually

584
00:42:29,000 --> 00:42:34,000
drink milk. How many
people here are lactose

585
00:42:34,000 --> 00:42:38,000
intolerant? It's nothing to be
ashamed of. I'm married to a very

586
00:42:38,000 --> 00:42:43,000
lactose intolerant person.
She's otherwise very nice.

587
00:42:43,000 --> 00:42:48,000
The fact is that the enzyme
to break down lactose,

588
00:42:48,000 --> 00:42:52,000
it's an enzyme which is called
lactase. And here we have yet

589
00:42:52,000 --> 00:42:57,000
another nomenclature item.
So lactase is the enzyme which

590
00:42:57,000 --> 00:43:02,000
breaks down lactose.
And, by the way,

591
00:43:02,000 --> 00:43:06,000
this is just the harbinger of many
other enzymes we're going to talk

592
00:43:06,000 --> 00:43:10,000
about in the future that
end in A-S-E. Whereas,

593
00:43:10,000 --> 00:43:14,000
carbohydrates, many of them end
in O-S-E, as you've already sensed.

594
00:43:14,000 --> 00:43:18,000
So it turns out that the enzyme
lactase is made in large amounts by

595
00:43:18,000 --> 00:43:22,000
most mammals very early in life.
Why? To be able to breakdown the

596
00:43:22,000 --> 00:43:27,000
milk sugar that comes
in their mother's milk.

597
00:43:27,000 --> 00:43:30,000
But once mammals are weaned there's
no reason on earth for them to

598
00:43:30,000 --> 00:43:34,000
continue to make lactase,
in their stomach for example.

599
00:43:34,000 --> 00:43:38,000
And, as a consequence, in most
mammals the production of lactase is

600
00:43:38,000 --> 00:43:42,000
shut down later in life. And
for some weird quirk of human

601
00:43:42,000 --> 00:43:46,000
history, a significant proportion
of humanity has learned how to retain

602
00:43:46,000 --> 00:43:50,000
the ability to make lactose
through adulthood. And,

603
00:43:50,000 --> 00:43:54,000
as a consequence, people
can go and have ice cream

604
00:43:54,000 --> 00:43:58,000
until the age of 70, 80
or 90 without becoming very

605
00:43:58,000 --> 00:44:02,000
bloated. And we don't
need to get into all

606
00:44:02,000 --> 00:44:06,000
the details, but you can begin
to imagine. And what happens is,

607
00:44:06,000 --> 00:44:10,000
therefore, the lactase enzyme
is shut down in their stomach.

608
00:44:10,000 --> 00:44:14,000
It depends. Sometimes they lose
it at the age of 10 or 15 or 20.

609
00:44:14,000 --> 00:44:18,000
And then, for the rest of their
lives, whenever they have a milk

610
00:44:18,000 --> 00:44:22,000
containing product, in
fact, my son is also lactose

611
00:44:22,000 --> 00:44:26,000
intolerant. I'm surrounded
by these people. Again,

612
00:44:26,000 --> 00:44:30,000
he is otherwise a tolerant person
but he's lactose intolerant.

613
00:44:30,000 --> 00:44:33,000
So this lactose molecule
will go into the stomach,

614
00:44:33,000 --> 00:44:37,000
it will remain undigested,
it will remain a disaccharide

615
00:44:37,000 --> 00:44:40,000
instead of being cleaved
into two monosaccharides.

616
00:44:40,000 --> 00:44:44,000
The two monosaccharides are no
problem because they can readily be

617
00:44:44,000 --> 00:44:47,000
interconverted. The
galactose can be readily

618
00:44:47,000 --> 00:44:51,000
converted into glucose,
and glucose is the universal

619
00:44:51,000 --> 00:44:54,000
currency of carbohydrate energy.
And so this disaccharide passes

620
00:44:54,000 --> 00:44:58,000
through the stomach unaltered
and it gets into the intestines,

621
00:44:58,000 --> 00:45:02,000
in the small intestine
and the large intestine.

622
00:45:02,000 --> 00:45:06,000
And it turns out we have more
bacterial cells in our gut than we

623
00:45:06,000 --> 00:45:10,000
have our own cells in the
rest of the body. Imagine that.

624
00:45:10,000 --> 00:45:14,000
And there are a lot of bacteria
that are waiting around in the gut

625
00:45:14,000 --> 00:45:19,000
for just a little gulp of lactose.
And they never get it because most

626
00:45:19,000 --> 00:45:23,000
people break down their lactose long
before it gets into the intestine.

627
00:45:23,000 --> 00:45:28,000
But here we have these
lactose intolerant people.

628
00:45:28,000 --> 00:45:31,000
The disaccharide gets into the
gut and the bacteria go to town.

629
00:45:31,000 --> 00:45:35,000
They've been waiting around for
years, decades for a little bit of

630
00:45:35,000 --> 00:45:39,000
lactose. And now it finally
arrives and they go to town,

631
00:45:39,000 --> 00:45:43,000
ad they start metabolizing it and
they ferment and they produce lots

632
00:45:43,000 --> 00:45:46,000
of gas and other kinds of
byproducts. And, as a consequence,

633
00:45:46,000 --> 00:45:50,000
this makes people very
uncomfortable. Just to show you,

634
00:45:50,000 --> 00:45:54,000
now, the fact is that lactose
intolerance people can perfectly

635
00:45:54,000 --> 00:45:58,000
well break down sucrose,
obviously. This is one of the great

636
00:45:58,000 --> 00:46:01,000
energy sources from plants.
But they cannot break this down.

637
00:46:01,000 --> 00:46:05,000
And I emphasize that point to
indicate that the stereochemical

638
00:46:05,000 --> 00:46:09,000
differences between different
kinds of carbohydrates makes a very

639
00:46:09,000 --> 00:46:13,000
important difference. An
enzyme like sucrase will break

640
00:46:13,000 --> 00:46:17,000
down the sucrose but it
will not touch lactose.

641
00:46:17,000 --> 00:46:21,000
So there's a high degree of
stereospecificity as it's called in

642
00:46:21,000 --> 00:46:25,000
the trade. Here we now go to
another step forward that we're

643
00:46:25,000 --> 00:46:29,000
going to pursue in much
greater detail next time.

644
00:46:29,000 --> 00:46:33,000
Because here, for the first time,
we talk about polymerization. We're

645
00:46:33,000 --> 00:46:38,000
making polymers. Where the
large number of hydroxyl

646
00:46:38,000 --> 00:46:43,000
groups on these monosaccharides
affords one many opportunities to

647
00:46:43,000 --> 00:46:48,000
make very long linear aggregates
end-to-end like this or even side

648
00:46:48,000 --> 00:46:53,000
branches. If you imagine that
each one of these hydroxyls,

649
00:46:53,000 --> 00:46:58,000
in principle, represents a site
for possible esterification,

650
00:46:58,000 --> 00:47:03,000
i.e., the formation of a bond
to a neighboring side chain.

651
00:47:03,000 --> 00:47:08,000
Here we see these two linear chains
and here we see the branch which is

652
00:47:08,000 --> 00:47:13,000
afforded, which is made possible by
the availability of these unutilized

653
00:47:13,000 --> 00:47:18,000
hydroxyl side chains which are
just waiting around to participate,

654
00:47:18,000 --> 00:47:23,000
if the opportunity allows them,
in some kind of esterification

655
00:47:23,000 --> 00:47:28,000
reaction to form a covalent bond.
Here is, by the way, glycogen,

656
00:47:28,000 --> 00:47:34,000
which is the way we store
a lot of sugar in our liver.

657
00:47:34,000 --> 00:47:38,000
Here's a starch, which
is what we get from many

658
00:47:38,000 --> 00:47:43,000
plants. And here's another
very interesting polysaccharide.

659
00:47:43,000 --> 00:47:47,000
It's called cellulose. And
we cannot digest cellulose,

660
00:47:47,000 --> 00:47:52,000
but termites can. And why they
can is something we'll have to wait

661
00:47:52,000 --> 00:47:56,000
until next time to learn about.
Have a great weekend. See you on

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Monday.