OK.  So today we're going to spend a little bit of time on some  
elementary chemistry just to develop our language that we use with one  
another.  And so when I say hydrogen bond, you don't stare blankly at me  
and scratch your heads.  Many of you have had this already.   
For many of you this is a review,  but it's a useful review.   
We believe here at MIT of teaching things two or three times often,   
the same subject matter, but at increasing levels of sophistication.   
So I do this without apology.  Our first issue here is how are  
atoms and molecules held together?  And the most familiar way by which  
atoms and molecules are held together is, of course,   
the covalent bonds.  And covalent bonds have an energy of roughly 80  
kilocalories per mole.  And that's a rather strong energy to  
hold together two atoms because the energy, the thermal energy,   
that is the energy at, let's say,  body temperature is about 0.6  
kilocalories per mole.  And, therefore, if you had a bond,   
if there was something holding things together that was in this  
range or two or three or four times higher then the simple thermal  
energy at room temperature or at body temperature would be sufficient  
to break apart such a bond.  But, in fact, this energy,   
the energy of a covalent bond is so much higher that it's highly  
unlikely that thermal energy is going to break apart a preexisting  
covalent bond.  And I was just reading yesterday  
about how people were analyzing the mitochondrial DNA from some  
Neanderthal bones which were dug up.  The last Neanderthal lived around  
30,000 years ago, our recently demised cousins.   
And they were analyzing the DNA sequences.  And they got out of  
those analyses stretches of DNA that were 200, 300 nucleotides long.   
And that really is stunning testimonial to the fact that under  
very difficult conditions,  nonetheless, complex biological  
molecules are able to survive over astounding periods of time,   
indeed those that are held together by the covalent bonds like this.   
Of course, you remember the film Jurassic Park where they used PCR  
reaction to resurrect the DNA of dinosaurs.  That's a bit of a  
fantasy since dinosaurs left us,  I guess, about 150 million years ago,   
something like that.  There's a big difference,   
obviously, between 300,000 and 150 million year ago.   
Now, the fact is if you look at the way that molecules are actually  
hooked up, for instance,  let's look at a water molecule here.   
Ideally there should be no charge on this molecule.   
And, in fact, there is no net charge.  But the truth of the matter  
is, if one wants to get frank,  that oxygen molecules, and we always  
are here, that oxygen molecules have a greater affinity for electrons  
than do hydrogen atoms,  i.e., they are electronegative.   
And, therefore, what this means is that the swarms of electrons that  
are holding all this together at the orbitals are drawn more closely to  
the oxygen and the hydrogen atoms,  i.e., the protons are relatively  
willing to give up their electrons.  And what this means is that there's  
an unequal distribution.  And, as a consequence, there is a  
fraction of a negative charge here at this end of the molecule and  
there are fractions of positive charges here because it's not as if  
they've totally given up the electrons, but the electrons are  
shifted more in this direction.  And this molecule is therefore  
called a polar molecule by virtue of the fact that here it has a positive  
pole and here it has a negative pole.  There are other pairs of molecules  
which are relatively equally electronegative.   
For example, here,  if we have a carbon and a hydrogen,   
these two atoms are roughly equally matched in terms of their ability to  
pull electrons away,  one from the other.  And,   
as a consequence, there is no net shifting of charge.   
And keep in mind that this delta I show here is only a fraction of an  
electronic charge.  It's not the entire electronic  
charge moved over.  But this has important consequences  
for the entire biochemistry that we're about to get into both today  
and on Monday.  Important because polar molecules,   
such as water like this, are able to dissolve certain compounds.   
And nonpolar molecules, which have large arrays of these kinds of bonds  
or carbon-carbon bonds,  these are relatively insoluble in  
water, and that has important consequences for the organization of  
biological membranes.  We might have a carbonyl bond here,   
that is a C going to an O via a double bond.  And here we have,   
once again, a situation where the oxygen is far more avid in terms of  
its willingness and interest in pulling electrons toward itself.   
And, therefore, the carbon gives up a little bit of the electron cloud  
and it becomes slightly electropositive.   
Whereas, the oxygen atom becomes slightly electronegative.   
Now, the fact of the matter is that there are also other bonds that are  
noncovalent and are much less energetic.  For example,   
let's talk for a moment about a hydrogen bond.   
And it's perhaps easiest to demonstrate a hydrogen bond by  
looking at the structure of two neighboring water molecules in a  
solution of water of all things.  And, the fact of the matter is,   
let's say we draw one water molecule down here and one water molecule  
down here.  What will happen is that this oxygen atom over here by virtue  
of its electronegativity will have a certain affinity for pulling this  
hydrogen atom toward itself.  And, in fact, what actually happens  
in real life, whatever that is at the molecular level,   
is that this hydrogen atom may actually be bouncing back and forth  
between these two oxygens.  It may be rapidly an interchange  
between them.  This interchange causes a strong association between  
two neighboring water molecules.  And, indeed, represents the reason  
why water does not vaporize at room temperature because the water  
molecules have a strong affinity or an avidity for one another.   
And, therefore, just to take some illustrations out of the book,   
this is the way it's illustrated in the book.   
Probably good to have a screen down.  And here you can see the way that  
water molecules are actually arrayed in water.  This is the lower  
illustration here.  Just to indicate to you that the  
hydrogen atoms are not really the possession, the ownership of one  
molecule of water.  They're just constantly being  
exchanged back and forth.  And this back and forth exchange,   
this sharing of a hydrogen atom is what enables a hydrogen bond of  
roughly 5 kilocalories of energy per mole to hold things together.   
5 kilocalories is not much.  It's only one order of magnitude  
above 0.6 rather than being two orders of magnitude.   
And, therefore, if one raises the temperature to the level of boiling,   
if the temperature is high enough,  the thermal energy is high enough to  
rip apart these kinds of associations.   
Now, if we were to go back here to look at this carbonyl atom we would  
find the following sort of situation.  Here we have this unequal sharing  
of electropositive and electronegative bonds.   
Let's put an acidic group like this.  This is a carboxylic acid right  
here.  Here we see a carbon bond to a hydroxyl here via  
this oxygen atom.  Here, once again,   
we have an electronegative atom.  And, in fact, if we talk about an  
ionized acid, normally in the absence of ionization there would be  
a net zero charge right here.  But at neutral pH it may well be  
the case that the association,  for various reasons, between this  
oxygen and this hydrogen will allow the hydrogen, or rather the proton,   
the nucleus of the hydrogen atom to just wander away.   
And, therefore, we can imagine there could be a net negative  
charge here.  A whole, this has one full electron,   
electronegative charge here, the charge of one electron,   
and this proton will have ionized,  will have left the carboxylic group  
in which it originated,  and now we have an ionized acid  
group.  Either before or even after this ionization,   
there is a strong affinity of the carboxyl group with the water around  
it because let's look at what happened before the ionization  
occurred.  This carbon here is strong and  
electronegative.  And, therefore, it will participate  
in hydrogen bonding to the water solvent here, i.   
., this proton will be shared a bit between the oxygen of the water  
molecule and the oxygen right here.  Similarly, here this oxygen will be  
slightly electronegative for the reasons I've just described.   
And here, once again, there may be some weak hydrogen bonding going on.   
Although, not as effective as over here where we have a double-bond  
where we have a lot of concentration of a cloud of electrons pulled  
towards the oxygen atom.  And this begins to give us clues as  
to why certain molecules are soluble in water and others are insoluble.   
For example, if we look at aliphatic compounds.   
Let's look at a compound that's structured like this.   
 I guess most people would call this  
pentane.  And we can call it that,  too.  And this has no  
electronegativity or positivity by virtue of the equal affinities of  
these two kinds of atoms,  that is the hydrogen and the carbons  
for electrons.  And as a consequence,   
this will not be able to form any hydrogen bonds with a solvent around  
it if the solvent happens to be water.   
So there's not good bonding here.  And this will, in fact, also if one  
puts this in a solution of water,  this will cause all the water  
molecules to line up in a certain way, almost a quasi-crystal around  
the aliphatic molecule.  They'll be ordered in a certain  
layer around the aliphatic molecule without being able to form any  
strong hydrogen bonds with them.  And this ordering represents a loss  
of chaos, a loss of entropy.  Entropy is chaos.  It's disorder.   
It's what happens, let's say, at 10:55 when we all leave the room,   
all of a sudden order becomes chaotic.  And here,   
before this lining up occurred,  the water molecules were chaotically  
arrayed throughout the solvent.  After this lining up occurred there  
was a loss of entropy, there was a loss of chaos.   
And thermodynamics tells us that generally the ordering of molecules  
is disfavored.  And consequently we now have two  
reasons why this molecule doesn't like to be in the midst of water.   
First of all, it's unable to form hydrogen bonds with the solvent.   
And second of all there is a decrease in the entropy,   
in the chaos that occurs when this molecule directly confronts water.   
And because of those two reasons it turns out that this molecule doesn't  
like to be in water.  The aliphatic molecule,   
as one would call this in organic chemistry, doesn't like to be in  
water.  And a dislike of water is often called its hydrophobicity,   
or we often call it hydro, might as well spell it right,   
hydrophobic, i.e., it really hates to be in water.   
In fact, class,  there's a second meaning for  
hydrophobia, or hydrophobic has a second meaning.   
Every five years I ask a class to see who knows what the second  
meaning of hydrophobia is.  This is really obscure.  Sorry?   
Rabies, right.  The TAs aren't allowed to answer that.   
If somebody has rabies,  at one stage of rabies, almost near  
the terminal stage,  the individual becomes hydrophobic  
because he or she doesn't like to drink water, for reasons that are  
obscure at least to me.  Now, conversely,   
molecules that have carboxyl group on it would be called hydrophilic.   
And, as we'll see over this lecture and the next one,   
these hydrophobic and hydrophilic tendencies tend to have great  
affects on the overall behavior of molecules.  Let's,   
for example, imagine a situation where we have a long aliphatic tail  
like this.  In fact,  these tails can go on in certain  
aliphatic compounds.  They can go on for 20 or even 30  
carbons.  And at the end of this,  let's just put arbitrarily a  
carboxyl group.  And let's say we ionized it.   
So here's an acidic group that's ionized.  It's shed its proton.   
It's actually acquired a negative charge.  And now we have something,   
this molecule is a bit schizoid.  Because on one end of it,   
it loves to be in water, the other end of it hates to be in water.   
And this has strong affects.  It's sometimes called amphipathic,   
but we don't need to worry about that word.  And,   
therefore, this carboxyl head loves to stick its head,   
to immerse its head in water.  And these things, the aliphatic  
portion hates to be in water.  Now, as a consequence of these  
rather conflicted feelings that these molecules have about water,   
we can ask the question what happens when we put such molecules  
actually into water?  And what we see here is the  
following.  That if we were to construct, for example,   
a molecule of the sort that has here,  in this case we're talking about a  
molecule that has two hydrophobic tails.  We'll get into its detailed  
structure shortly,  but just imagine for a moment two  
long hydrophobic tails out here ended with a hydrophilic head.   
And under such situations,  if we put thousands of these or  
millions of these molecules into a solution of water,   
what we will then see is,  no pointer?  All right.  Pointer?   
All right.  What we will then see is that the hydrophilic head groups,   
which are here depicted in red, will point their way outwards,   
they will want to stick their heads in water.   
And conversely the hydrophobic tails fleeing from the water will actually  
associate one with the other.  And so you have a structure that's  
called, in this case,  an a micelle where you form this  
little globular sphere where the lipid tails are tucked inside.   
And, therefore, are actually being shielded from any direct exposure to  
water.  This structure down here,  the lipid bilayer, is actually, as  
we will discuss in greater detail shortly, the overall topology of the  
way most biological membranes are organized.   
In fact, virtually all of them.  Why is that?  Because biological  
membranes separate two hydrophilic or two aqueous spaces.   
Thank you, sir.  A gentleman you are.  So here is an aqueous space  
and here is an aqueous space.  And as we see the hydrophilic heads  
are immersed or sticking their heads into the hydrophilic space.   
This is called a lipid bilayer.  And, obviously, it's highly  
effective for separately these two aqueous compartments.   
In eukaryotic cells, as I mentioned last time, there is an enormous  
premium placed on separating and segregating different aqueous  
compartments which is invariably achieved through the device of  
constructing these lipid bilayers.  Here's a vesicle.  A vesicle is  
more complicated than a micelle.  Because if you look at the membrane  
lining the vesicle,  you see it's actually a lipid  
bilayer, but one that in 3-dimensional space is actually a  
sphere.  And in the case of this vesicle, we can well imagine that on  
the inside of the vesicle water is kept, can be stored,   
and on the outside of the vesicle water can be stored.   
And many of the membranes that we see within the cytoplasms themselves  
are actually constructed on this kind of design.   
So when we draw,  for example, in this case the Golgi  
apparatus, which I mentioned to you in passing last time we met,   
each one of these membranes here,  it's obviously drawn as a double  
line, but whenever you see a membrane indicated,   
implicit in that drawing is the fact that each one of these membranes is  
actually a bilayer.  There are never any monolayers of  
lipids in living cells.  Each one of these vesicles you see  
here is actually a lipid bilayer with an aqueous inside and,   
once again, aqueous on the outside.  Again, much of the thermodynamic  
stability that allows these vesicles to remain intact rather than just  
diffuse apart is created by these hydrophilic and hydrophobic forces  
which tie such molecules together or will rip them apart.   
Now, in truth there are yet other kinds of forces that govern the  
affinity of molecules to one another.  For example, let's imagine a  
situation where we have an ionized acid group of the sort we just  
talked about before.  Now, by the way,   
here, let's say I'll draw the negative charge on one of these two  
oxygens, if you can see that.  But the truth is that the electrons  
are swarming back and forth,  and so the negative charge is shared  
equally, the negative one electron charge is shared equally between  
these two oxygen atoms.  And this is obviously an area of  
great electronegativity.  Independent of that,   
let's imagine up here we have a basic group, let's say an amine  
group over here.  And, the fact of the matter is,   
amine groups, NH2 groups, that's what an amine is,   
here's an amine group.  This is a carboxylic group.   
And the amine group, which is used very often in biochemistry,   
actually has an affinity.  It has an unpaired set of electrons on the  
nitrogen, and so it likes to attract protons to it,   
which makes it,  causes it to be called basic.   
And this attraction,  the scavenging of protons,   
perhaps from the water, will obviously give this whole group here  
a net positive charge,  a charge equal to the charge of one  
proton.  Here,  once again, we can imagine this is  
hydrophilic because this charge group can once again also associate  
quite intimately with aqueous solvent.   
Now, independent of any other forces that might exist here,   
indeed one could imagine situations where there is a sharing of a proton.   
And, therefore,  a hydrogen bond formed between these  
two.  Independent of that is the simple electrostatic interaction of  
these two groups.  That is the mutual attraction of  
positive and negative groups,  one to the other.  And the  
electrostatic interactions,  you cannot quantify exactly how many  
kilocalories a mole there is because the energetic value in electrostatic  
interaction is equal to one over r squared where r is the distance  
between these two charged groups.  And obviously the further apart you  
get the weaker the attraction with one another.  There are also what  
are called van der Walls interactions.  There are largely of  
interest to a very small community of biochemists.   
You probably will never,  you may never hear this term again  
in your life.  And van der Waals interactions come  
from the fact that if we were to have, for example,   
two molecules over here which are not normally charged in any way,   
let's just talk about two aliphatic chains again.  And I won't put in  
all the protons and everything,  but just imagine a situation like  
this.  What will happen is that because of the fluctuations of  
electrons, because the electrons are swimming around here all the time,   
moving from one area to the next they're never equally distributed  
homogenously over a long period of time, there will be brief instance  
in time, microseconds or even nanoseconds when there happens to be  
more electrons over here than right here.   
Just by chance.  And this area of unequal  
distribution of electrons will in turn induce the opposite kind of  
electron shift in a neighboring molecule down here.   
Obviously, depending on the distance between them.   
But the negative here will repel electrons down here.   
The positive here will attract electrons down here.   
And so you will have these two quasi-polar arrangements here and  
here, very ephemeral,  that is lasting for a very short  
transient period of time.  But, nonetheless, sufficient to  
give a very weak interaction between these two molecules which may  
persist only for a microsecond and then be dissipated because the  
charges then redistributed once again.   
And, as a consequence of that,  one has very weak interactions which,   
in the great scheme of things,  play only a very minor role in the  
overall energy which holds molecules together.  Now,   
with that background in mind,  let's begin to elaborate on it,   
on how we can make molecules that have interesting properties that  
enable them, among other things,  to participate in the construction  
of lipid bilayers,  which will be the first object of  
our attentions today in terms of actual biochemistry.   
So here's a fatty acid.  We see that up here.  I,   
in effect, drew you the structure of a fatty acid up here already once  
before.  And what we can see is through a linkage known as  
esterification we can create this molecule.  So what do I  
mean by esterification?  Well, in this case we're talking  
about a situation here where we have a carbon atom over here like this  
with a hydroxyl group.  You see it over here.  And what  
we're doing is we're dehydrating this, we're pulling out one net  
molecule of water.  And each time we do that,   
on three separate occasions,  what we end up doing is to create  
instead of this is to create a covalent bond between these two.   
And so the end product of dehydrating this,   
pulling out one net molecule of water is that we end up with a  
structure that looks like this.    
And you see that happening on at least three different occasions,   
here, here and here.  Well, actually,  I should put a carbon over here.   
So here we have three esterifications.   
The hydroxyl group in each case is reacting with a carboxyl group here  
pulling out one water,  and each case creating what's called  
triacylglyercol or triglyceride.  Triglyceride refers to the fact  
that we started here with a glycerol and we have now esterified it.   
Now, in fact, there are two directions here in this  
kind of reaction.  Esterification is the kind of  
linkage that we just showed here.  And the truth is that vast numbers  
of biochemical linkages are made by esterification reactions and  
reversed by reactions that are called simply hydrolysis.   
And, in this case, what we're referring to is the fact that if one  
were to reintroduce a water molecule into each of these three linkages,   
one, two and three, we would break the bond and cause this entire  
structure to revert to the two precursors that existed or  
preexisted prior to these three esterification reactions.   
And time and again you'll see,  over the next weeks, that  
esterification reactions are important for constructing different  
kinds of molecules.  Now, the fact of the matter is we  
can do other kinds of modifications of a glycerol like this.   
Here what we've done,  instead of adding a third fatty acid,   
note what was done here.  Here through an esterification,   
let's look up at this one here,  instead of adding a third fatty acid,   
we've saved, we've reserved one of the three groups of the glycerol.   
Here's what we saw just before.  We've saved one of the three groups  
of the glycerol and put on instead this highly hydrophilic phosphate  
group, once again through a dehydration reaction, an  
esterification reaction.  And now what we've done is add  
insult to injury because in the absence of this phosphate it would  
have a hydroxyl here which is mildly hydrophilic.  But now look how  
strongly charged this is.  Here are two negative charges,   
one electron each.  And this is already a bit electronegative.   
So here we have an extremely potent hydrophilic entity.   
And here the degree of schizophrenia between one end of the  
molecule and the other is greatly exaggerated.  Here,   
in fact, this is extremely hydrophilic.   
And, as a consequence of that,  this really likes to stick its head  
inside water.  And when we therefore talk about, we draw the images of  
different kinds of membranes,  like this I showed you before the  
two tails.  Here you saw the two tails I drew before in that diagram.   
Here's what we can imagine they actually look like in more real  
molecular terms.  And the hydrophilic heads sticking  
in the water, this is just repeating what we saw before,   
become even more hydrophilic if we look at a molecule like this.   
Let's look at this thing here.  Here's a very long hydrophobic tail.   
Here are the two glycerols once again.  Here is the phosphate.   
And keep in mind that phosphate obviously has these extra oxygens.   
Phosphate can react with more than just one partner,   
the glycerol down here.  In this case we've added this group  
up here.  And this group up here is,  once again, this happens to be a  
serine which is an amino acid,  this also happens to be quite  
hydrophilic.  Here's our old friend the basic  
amino group.  Here's the carboxyl group.  This is a bit hydrophobic,   
CH2.  And then we once again have the hydrophilic head here.   
And, therefore, we imagine,  if we look at what's called a  
space-filling model,  and a space-filling model really is  
intended to show us what one imagines if one had this vision,   
which we don't have, how much space each of these atoms would actually  
take up if one were able to see them.   
And here we see this space filling model.  This lipid molecule here is  
actually slightly kinked with its hydrophilic head tucked into the  
water space.  And so here's actually the way that many biological  
membranes look in terms of the way that they are constructed.   
Now, the fact of the matter is this also affords the cell the ability to  
segregate contents on one or the other side of whatever lipid bilayer  
it happens to have constructed.  And here we can see about the  
semi-permeability,  how permeable these membranes are to  
different kinds of molecules.  Permeability obviously refers to  
the ability of this membrane to obstruct or to allow the migration  
of molecules from one side to the other.   
Ions, and these ions we see right here are obviously highly  
hydrophilic by virtue of their charge.  That's explains,   
in fact, why, for example,  table salt goes so readily into  
solution, because it readily ionizes into sodium, NA and CL,   
which then are avidly taken up by the water molecules.   
So these are highly hydrophilic ions.  And the questions is,   
can they go from one side of the membrane to the other?   
And the answer is absolutely not or highly improbably.  Why?   
Because these are so highly hydrophilic, the water molecules  
love to gather around them and form hydrogen bonds and electrostatic  
bonds with them.  And if one of these ions ventures  
over here, it's going from an area where it's warmly embraced by the  
solvent molecules to an area where these molecules intensely dislike  
these ions.  And,  therefore, thermodynamically the  
entrance of any one of these ions into the membrane,   
into the hydrophobic portion of the membrane is highly disfavored,   
which makes the membrane essentially,  for all practical purposes,   
impermeable.  The same can be said of glucose  
which happens to be a carbohydrate.  We'll talk about it shortly.  But  
it's also nicely hydrophilic.  It also can go in water.  In fact,   
it can go through.  And it's actually the case,   
to my knowledge, that one doesn't really understand to this day why  
lipid bilayers are reasonably permeable to water.   
You would say, well,  water shouldn't be able to go  
through.  It clearly doesn't have to have a  
net positive or negative charge,  but the physical chemist, if you  
asked them why does water,  why is water able to go through  
lipid bilayers?  They'll say, well,   
we've been working on that and we'll get you an answer in the next five  
or ten years.  And they said that 40 years ago and 30 years ago,   
and they're still saying it.  And we don't really understand why  
water goes through,  which is an embarrassment because  
here's one of the fundamental biochemical properties of living  
matter that is poorly understood.  Gases can go right through.   
And amino acids,  ATP, glucose 6 phosphate,   
highly hydrophilic, can also not go through.  Now,   
the advantage of this is that a cell can accumulate large concentrations  
of these molecules either on the inside or it can pump them to the  
outside.  In other words,  it can create great gradients in the  
concentrations of different kinds of ions.  For example,   
in many cells, the concentration of calcium, CA++ is a thousand times  
higher on the outside of the cell than on the inside of the cell which  
is a testimonial to how impermeable these lipid bilayer membranes are.   
The fact of the matter is I'm fudging a little bit here because in  
the lipid bilayers of the plasma membrane of the cell,   
the outer membrane of the cell that we talked about in passing last time,   
there are ion pumps which are constantly working away pumping ions  
from one side to the other overcomes the little bit of leakage which may  
have occurred if a calcium ion happens to have snuck through in one  
direction or the other.  And we end up expending a lot of  
energy to keep these ion gradients in appropriate concentrations on the  
outside and the inside.  In fact, virtually all the energy  
that is expended in our brain,  almost all of it is expended to  
power the ion pumps which are constantly insuring that the  
concentrations of certain ions on the outside and the inside of  
neurons are kept at their proper respective levels.   
It could therefore be that actually more than half of our metabolic  
burden every day is expended just keeping the ions segregated on the  
outside and inside of cells.  For example, potassium is at high  
levels inside cells,  sodium is at high levels outside  
cells, just to site some arbitrary examples.  There are also,   
by the way, as I mentioned last time,  channels.   
And channels are actually just little doughnut shaped objects which  
are placed, inserted into lipid bilayers in the plasma membranes and  
just allow for the passive diffusion of an ion through them,   
through the doughnut hole enabling an ion, so if here's the lipid  
bilayer, not showing its two things,  these kinds of doughnut shaped  
protein aggregates will allow the passage of ions in one  
direction or another.  And here energy is not being  
expended to enable this passage.  It may just be through diffusion.   
If there's a higher concentration of ion on side of the lipid bilayer  
and a lower one on this side,  this diffusion will allow the ion to  
migrate through the bore of the ion channel from one side to the other.   
In fact, even though this does not involve the expenditure of energy on  
the part of the cell,  the cell may actually use a gating  
mechanism to open or close these channels.   
When the channels are closed then the ions cannot move through.   
When the channels are gated open then diffusion can take over and  
insure the transfer,  the transportation of ions from one  
side to the other.  Now, having said that,   
we can begin to look at yet other higher level structures.   
Here, by the way, is a better drawing than the one I provided you.   
This comes from your book of what a vesicle looks like.   
Here's what it looks like under the electron microscope and here's what  
it looks like when a talented rather than hapless and hopeless artist  
like myself tries to draw it.  So let's just say that's our intro  
into lipids and membranes.  And let's move onto the next layer  
of complexity.  And the next layer of complexity in  
terms of molecules represents carbohydrates.   
And when we talk about a carbohydrate amongst ourselves we're  
talking about a molecule which,  roughly speaking, has one carbon  
atom for every water molecule.  And we'll shortly indulge ourselves  
in talking about all kinds of different carbohydrate molecules.   
Here is really one of the most important carbohydrate molecules,   
glucose.  And what should we note about glucose?   
Well, the first thing you should see is that glucose has six carbon  
atoms.  And, therefore,  as a consequence it's called a  
hexose.  We're going to talk about pentoses  
very shortly.  They only have five,  to state the obvious.  Glycerol,   
which we talked about before,  is also considered in one sense a  
carbohydrate, but it's been called by some people a triose.   
It only has three carbon atoms.  And you can imagine, therefore, in  
principal that there are certain biochemical mechanisms which indeed  
exist which enable one to join two glycerol molecules,   
one to the other, to create something like a hexose, glucose.   
In fact, what we see from this drawing, expertly drawn by yours  
truly, is that the hexose molecule isn't really a linear molecule in  
solution.  What happens is that because of various steric and  
thermodynamic forces it likes to cyclize.  So let me just mention,   
I've just used two words that are useful to know about.   
Steric or stereochemistry refers to the 3-dimensional structure of a  
molecule.  And,  obviously, the stereochemistry of a  
molecule is dictated by the flexibility with which participating  
atoms can form bonds,  whether we have a trivalent atom  
like nitrogen or a tetravalent atom like carbon or a monovalent  
like hydrogen.  And these structures,   
the stereochemistry is dictated both by what atoms are present here and  
by thermodynamic considerations which cause this particular hexose,   
indeed virtually all hexoses, to cyclize.  When I say cyclize,   
obviously I mean to form a circular structure.  Here we note one thing.   
You can see how the hydroxyl here actually attacks the positively  
charged carbon here in order to form this cyclic structure.   
You see one of the six points on this hexagonal structure here is  
oxygen.  It's not carbon at all.  So there is one oxygen and five  
carbons.  And one of the carbons is relegated, is exiled to outside of  
the circle.  It's sometimes called an extracyclic because it's sticking  
out from the actual circle.  And this is the structure in which  
glucose actually exists inside cells.  And, in fact,   
there is, in truth,  two alternative ways by which  
glucose can cyclize,  whether the oxygen attacks the  
carbon on the carbonyl group underneath or on top.   
And you see that gives us two alternative structures.   
What's different about them?  Well, if we think about this hexose  
as existing in a plane,  or the hexagon is in a plane  
In this case the oxygen is above the plane and the hydrogen is below the  
plane.  With equal probability you can have these two atoms reversed  
where hydrogen is now above the plane and hydroxyl is below the  
plane.  And both of these structures,  these alternative structures can  
fairly be considered to be glucose.  Now, let's get a little bit more  
complicated.  Here we have fructose and we have galactose.   
And what we see here is,  by the way, that we have exactly the  
same number of carbon atoms and hydrogen atoms and oxygen atoms but  
they're hooked up slightly differently.  And here now we begin  
to get very picky about the disposition, the orientation of  
these different kinds of hydroxyls and hydrogens.   
And note, by the way,  here that in many cases one doesn't  
even put in the H for the hydrogen.  It's just implied by the end of  
this line.  And here, if you were to look at  
this, you'll see here now we have two extra cyclic carbons.   
Here's galactose which is yet another hexose.   
These are all hexoses,  but their stereochemistry creates  
quite different kinds of structures.  And it turns out that this  
stereochemistry is extremely important.  These molecules function  
very differently, one from the other.   
And, for example,  to the extent that glucose is used  
in different kinds of energy metabolism and to the extent that  
galactose is not,  there must be certain biochemical  
mechanisms in which one has catalysts, the catalysts that we  
call enzymes that ensure that one can convert one of these hexoses  
through an enzyme into,  let's say a less useful one into a  
more useful one,  glucose, which can readily be burnt  
up by the energy-generating machinery.  Here we've gone yet  
another order of magnitude more complex because we've gone from a  
monosaccharide,  i.e., one or another hexose,   
to a disaccharide.  And here's common table sugar.   
And here you see that it's formed once again through an esterification  
reaction, i.e.  there is a dehydration reaction  
between this hydroxyl here and this hydroxyl here.   
And biochemists take the orientation of these hydroxyl and  
hydrogen groups very seriously.  Now, you can say they're a bit  
obsessive.  Indeed they probably are.   
But, nonetheless,  we can admit that the specific  
orientations of all these things dictate very importantly the  
difference between here,  in this case sucrose, and in this  
case lactose.  Why is this important?  Well, this is the sugar in milk  
sugar.  This is the dominant sugar in milk sugar,   
lactose.  And half the world,  as adults, cannot absorb this.   
All kinds of unpleasant things happen when they actually  
drink milk.  How many people here are lactose  
intolerant?  It's nothing to be ashamed of.  I'm married to a very  
lactose intolerant person.  She's otherwise very nice.   
The fact is that the enzyme to break down lactose,   
it's an enzyme which is called lactase.  And here we have yet  
another nomenclature item.  So lactase is the enzyme which  
breaks down lactose.  And, by the way,   
this is just the harbinger of many other enzymes we're going to talk  
about in the future that end in A-S-E.  Whereas,   
carbohydrates, many of them end in O-S-E, as you've already sensed.   
So it turns out that the enzyme lactase is made in large amounts by  
most mammals very early in life.  Why?  To be able to breakdown the  
milk sugar that comes in their mother's milk.   
But once mammals are weaned there's no reason on earth for them to  
continue to make lactase,  in their stomach for example.   
And, as a consequence, in most mammals the production of lactase is  
shut down later in life.  And for some weird quirk of human  
history, a significant proportion of humanity has learned how to retain  
the ability to make lactose through adulthood.  And,   
as a consequence,  people can go and have ice cream  
until the age of 70,  80 or 90 without becoming very  
bloated.  And we don't need to get into all  
the details, but you can begin to imagine.  And what happens is,   
therefore, the lactase enzyme is shut down in their stomach.   
It depends.  Sometimes they lose it at the age of 10 or 15 or 20.   
And then, for the rest of their lives, whenever they have a milk  
containing product,  in fact, my son is also lactose  
intolerant.  I'm surrounded by these people.  Again,   
he is otherwise a tolerant person but he's lactose intolerant.   
So this lactose molecule will go into the stomach,   
it will remain undigested,  it will remain a disaccharide  
instead of being cleaved into two monosaccharides.   
The two monosaccharides are no problem because they can readily be  
interconverted.  The galactose can be readily  
converted into glucose,  and glucose is the universal  
currency of carbohydrate energy.  And so this disaccharide passes  
through the stomach unaltered and it gets into the intestines,   
in the small intestine and the large intestine.   
And it turns out we have more bacterial cells in our gut than we  
have our own cells in the rest of the body.  Imagine that.   
And there are a lot of bacteria that are waiting around in the gut  
for just a little gulp of lactose.  And they never get it because most  
people break down their lactose long before it gets into the intestine.   
But here we have these lactose intolerant people.   
The disaccharide gets into the gut and the bacteria go to town.   
They've been waiting around for years, decades for a little bit of  
lactose.  And now it finally arrives and they go to town,   
ad they start metabolizing it and they ferment and they produce lots  
of gas and other kinds of byproducts.  And, as a consequence,   
this makes people very uncomfortable.  Just to show you,   
now, the fact is that lactose intolerance people can perfectly  
well break down sucrose,  obviously.  This is one of the great  
energy sources from plants.  But they cannot break this down.   
And I emphasize that point to indicate that the stereochemical  
differences between different kinds of carbohydrates makes a very  
important difference.  An enzyme like sucrase will break  
down the sucrose but it will not touch lactose.   
So there's a high degree of stereospecificity as it's called in  
the trade.  Here we now go to another step forward that we're  
going to pursue in much greater detail next time.   
Because here, for the first time,  we talk about polymerization.  We're  
making polymers.  Where the large number of hydroxyl  
groups on these monosaccharides affords one many opportunities to  
make very long linear aggregates end-to-end like this or even side  
branches.  If you imagine that each one of these hydroxyls,   
in principle, represents a site for possible esterification,   
i.e., the formation of a bond to a neighboring side chain.   
Here we see these two linear chains and here we see the branch which is  
afforded, which is made possible by the availability of these unutilized  
hydroxyl side chains which are just waiting around to participate,   
if the opportunity allows them,  in some kind of esterification  
reaction to form a covalent bond.  Here is, by the way, glycogen,   
which is the way we store a lot of sugar in our liver.   
Here's a starch,  which is what we get from many  
plants.  And here's another very interesting polysaccharide.   
It's called cellulose.  And we cannot digest cellulose,   
but termites can.  And why they can is something we'll have to wait  
until next time to learn about.  Have a great weekend.  See you on  
Monday.  
