HAZEL SIVE: Another truism of
biochemistry is that many of
the molecules within cells
are very large.
And they're called
macromolecules, to indicate this.
So macromolecules.
So these are often --
Biological molecules are
often macromolecules.
And these macromolecules
are often polymers--
not always--
where a polymer is some
kind of repeat of
a monomer "n" times.
And in formation of
macromolecules, there are two
kinds of reactions that
you need to know.
They are called condensation
and hydrolysis reactions.
And they go something
like this.
Condensation reactions
form bonds.
Hydrolysis reactions
break bonds.
And condensation reactions
go something like this.
If we call the monomer M, there
would be a monomer with
a hydroxyl group that interacts
with another monomer
that has a hydroxyl group.
And the outcome of that would
be a bond between the two
monomers, with the
release of water.
And the flip of that, during
a hydrolysis reaction, is
exactly the opposite, where this
dimonomer here, M-O-M,
where there's an ether bond
between the two monomers as
I've drawn it, called different
things-- we'll talk
about that--
adds water and then is broken
down into two monomers.
And so you should know a
condensation and a hydrolysis
reaction, because every reaction
that we talk about in
this course and in much of
biochemistry involves either
condensation or hydrolysis
reactions.
Often, both condensation or
hydrolysis require energy,
sometimes that they
release it.
So often, both often require
energy in order to proceed.
Okay.
Very good.
Let's move then to the second
topic that I'd like to discuss
today, which is the
first big class of
macromolecules, the lipids.
Lipids are a fascinating
class of macromolecules
essential for life.
They comprise about 5% of the
dry mass of a cell, the dry
mass referring to the mass
remaining after the water has
been removed.
And lipids are crucial--
and we discussed this briefly
last lecture--
for formation of the membranes
around the cell and around the
various organelles.
So lipids are required
for membranes.
They also serve as major energy
stores for the cells.
Their bonds are very
energy rich.
They are also involved in
various signaling processes.
We'll touch on this today
and later in the course.
And of course, they are involved
in insulation, both
in keeping the whole organism
warm-- if it's an animal,
during winter--
but also in insulating nerve
cells as nerve cells transmit
their signals by insulating
them, kind of like an
electrical wire is insulated
by plastic.
The condensation reactions
that form during lipid
formation often involve
synthesis of things called
triglycerides.
And triglycerides are formed
from glycerol.
And I'm going to warn you that
my chemical structures are
going to be casual.
We assume that you have enough
chemistry that if you know
that I write CH2OH, you
actually know that the
hydrogens are sticking out
around the carbon.
Okay?
That's my contract with you.
We assume you know enough
chemistry to deal with that.
If you don't, then please come
and see me or Dr. Sinha.
And to that glycerol is
added a fatty acid.
And the fatty acid has got a
hydroxyl group attached to a
carbonyl, which is attached to
a long-chain hydrocarbon,
where n is 16 to 20.
And this guy here is called
a fatty acid.
And out of the addition of
glycerol and the fatty acid--
I'm going to put a line between
the two so that you
can see the difference--
comes something called
a triglyceride.
And I'm going to draw this for
just one of the glycerol
carbon atoms.
And then the same thing is
true for all the others.
So you'll have CH2 at
the end, and then a
condensation reaction.
And we're going to write et
cetera here, being casual
about this.
And out of this comes
this triglyceride.
This reaction is a condensation
reaction.
It eliminates water.
It's a condensation reaction.
And it's also a
transesterification, where you
can see the ester bond formed
in the triglyceride.
I'm going to notate
triglycerides in a slightly
different way.
I'll show you this
in a moment.
But let's take a look at a
picture here so you can see
what it actually looks like.
Here's glycerol,
from your book.
And here is a fatty acid.
And here are the reactive
species interacting to give
you a condensation reaction and
joining up the glycerol to
the fatty acid.
And the glycerol then serves
as a backbone to have these
three chains of fatty acid.
Hence the name triglycerides.
Lipids are not, strictly
speaking, polymers.
And so what I said about
macromolecules being polymers
really doesn't hold
for lipids.
But the other principles do.
One of the things about lipids
is that they can be modified.
And they can be modified by
replacing one of the fatty
acid chains with something
that is polar.
So if you look at this
triglyceride, you can see at a
glance that it is really
hydrogens and carbons.
It's very non-polar.
There's a couple of
oxygens up here.
But there are so few relative
to the molecule that really
this is a very non-polar
molecule.
But you can change the
properties of lipids in an
extraordinary way by replacing
one of the fatty acid chains
with something polar.
And that is particularly
done in phospholipids.
And we're going to now draw a
triglyceride in a different
way, in shorthand, where the
glycerol is going to have a
horizontal bar and the fatty
acid chains are going to
emanate as vertical lines.
The triglyceride, your classic
one, is hydrophobic because it
is non-polar.
But you can also take one of
those side chains, or one of
those fatty acid chains,
and replace it
with a phosphate group.
So you can replace one fatty
acid with a phosphate, which
is highly charged.
And then you get something like
this, where the blob is
the phosphate group.
Phospholipids are the things
which make cell membranes.
And they make cell membranes
because they are on one end
polar, and on the other
end they're non-polar.
And so here on the top end,
they are polar and
hydrophilic.
And then the bottom
part is non-polar.
And this causes them to
self-associate so that the
polar groups face water
and the non-polar
groups face one another.
And these will spontaneously
form a lipid bilayer, the
thing that surrounds all of
the cell and all of the
organelles.
So they will go and
spontaneously associate into a
bilayered membrane, which we can
draw like this, using our
shorthand notation.
And what I've done is to now
put the hydrophobic or the
non-polar bits facing
one another.
And these polar bits are now
interacting with water.
So these are hydrophilic--
which I'm going to hyphenate.
And they are indeed interacting
with water.
Let's look at some pictures
to exemplify this.
Here is the chemical structure
of a phospholipid.
They're the long-chain
fatty acids.
And here's the phosphate
group.
This is actually a modified
phosphate group.
It's got a choline moiety,
which makes
it even more polar.
And here you go with this
little bit sticking out.
So you can see the shape of
the molecule has changed.
And also its electronegativity
has changed.
And here are these molecules
that spontaneously form this
lipid bilayer, the phospholipid
membrane, with
all the hydrophilic parts
sticking out and touching
water on either side and the
hydrophobic parts interacting
with one another.
I want to really make
a point that this is
not a double membrane.
This is a single membrane.
We talked last time about
mitochondria and the nucleus
having double membranes
around them.
That would be two of these.
This thing that we've got up
here is a single membrane.
This is what all cell membranes
and organelle
membranes look like.
That's an important
thing to realize.
The last thing I want
to mention --
Actually, the last thing
I want to mention about
triglycerides is that there
are a couple of different
kinds of triglyceride
chains which are
very important medically.
And you've heard of them.
There are saturated fats, where
the triglyceride chains
have got all single
carbon atoms.
And all of these completely
saturated--
in other words, there
are no double bonds.
Triglycerides with these
types of chains
tend to pack tightly.
And this gives them the property
of chemical stability
and confers on them a
high melting point.
So saturated fats
are often solid.
And this is bad.
These are bad for you.
In contrast, unsaturated fats
are sometimes good for you and
sometimes not.
So unsaturated fats all
have, somewhere, a
carbon double bond.
There are two kinds of
unsaturated fats.
There are cis-unsaturated
fats, where--
let's just put in some
extra bonds here--
where the other bonds that are
available to the carbons are
on the same side of
the molecule.
And you remember that there's
no free rotation around a
double bond.
So if that molecule looks like
that, it is stuck that way.
If it synthesized that way,
it's stuck that way.
On the other hand, there are
trans-unsaturated fats, where
the additional valencies of
carbon are on opposite sides
of the molecule.
Cis fats--
I'll show you a slide
in a moment--
so these have got
double bonds.
The cis fats pack poorly because
they are kinked.
And these have got a
low melting point.
And these are good for you.
The trans-fats, however, are
much more like the saturated
fats, and they pack tightly, et
cetera, high melting point.
And they are particularly
bad for you.
Trans-fats are very seldom
found in nature.
They are found in Twinkies
and other gourmet treats.
All right, let's look
at some structures
here from your book.
Saturated fats, you can see the
chains are all straight,
and they pack very tightly.
Cis-unsaturated fats, here's a
bend in the chain, and this
makes the molecules
pack loosely.
This is a steric, a spatial,
consideration.
And then if you look at
trans and cis fats,
here's oleic acid.
It's the same carbon chain.
But trans-oleic acid has
a straight chain,
cis-oleic has a bend.
They're both unsaturated fats.
And the question that I am sure
you have seen is whether
or not trans fat should be
removed from all food, and how
that can be done, and why
it is bad for you.
And now it's required that there
are ingredients posted
on various food so that you
know what you're eating.
And I'm going to tell you a
little bit about why trans fat
is bad for you.
But I have to introduce to you
another lipid and another
class of lipids in
order to do so.
And that's not the only reason
that I'm going to introduce
this other class of lipids.
I'm going to do it because it's
a very important class.
So a second class of lipids that
we should consider beyond
the triglycerides are
the steroids.
Steroids share a common
ring structure.
They are lipids with a common
ring structure.
And I have the slide up so you
can look at it even now.
Their precursor is
cholesterol.
And cholesterol is,
in fact, not bad.
It is an essential lipid.
And it's essential both for
formation of the membrane, and
all membranes, and it is also
crucial for signaling.
And if an organism develops
without cholesterol, it
develops with one eye.
You lack the whole midline that
divides you into two more
or less bilaterally
symmetric parts.
So cholesterol is a very
essential component.
Other things that come from
lipids are vitamin D, much in
the news also with regard to
preventing inflammation, and
various hormones.
Their structure's on the
board -- on the screen.
And you can see, in green, the
common ring structure with
various other groups attached,
which give these different
steroidal lipids their
particular structures.
And we'll come back to the
notion of cholesterol and why
it's both essential but--
let me annotate here--
too much is bad.
All right.
In the news a lot are steroids
androgens, a particular class
of artificial androgens
are normal steroids.
But there is a class of
artificial steroids.
Here's one,
tetrahydrogestrinone, which is
used by athletes.
It is mostly undetectable.
The tests for anabolic steroids
used by athletes are
actually very high tech.
And this one is very difficult
to detect.
And it makes the question of
whether particular athletes
have used steroids rather
difficult to answer
unequivocally.
Too much cholesterol --
I should be using the screen.
Too much cholesterol leads
to a condition called
atherosclerosis, where
cholesterol is deposited in
the arteries.
Here it is.
And this literally physically
blocks up the artery, causes
the blood to clot, and leads
to heart attacks.
And here's an artery
that's OK--
well, actually it's
not quite, there.
You can see it's being injected
with contrast, and
there's a little place
where it's not OK.
And here's one which is
completely occluded by an
atherosclerotic plaque.
What's the deal with
cholesterol?
Cholesterol is used for
membranes and signalling.
But it also is carried through
the body by a component called
low-density lipoprotein.
And this low-density
lipoprotein, or LDL, is
deposited in the arteries, where
it plugs them and leads
to heart attack.
If cholesterol binds
high-density lipoproteins, a
different kind of a transport
molecule, then the excess
cholesterol is excreted by the
liver, and you're good.
You're well.
Turns out, through complicated
reasons, that trans fat and
saturated fat increases the
levels of this bad,
low-density lipoprotein
and thereby
increases heart attacks.
I should note that most
cholesterol is made by you.
80% of your cholesterol
is made by you.
20% you get from food.
So eating a low cholesterol diet
usually doesn't do much
for cholesterol levels.
You actually have to interfere
with synthesis, which is what
the various drugs called
statins do.
All right.
So enough about lipids.
Let us move to our third topic
today, another fascinating and
important set of macromolecules,
the
carbohydrates.
Carbohydrates make up
about 25% of the dry
mass of a cell .
They're used as an energy
source, as a carbon source to
build other molecules.
And they also encode
information, as in your blood
type, which I will try to touch
on in a few moments.
Their chemical formula is much
simpler and is polymeric,
unlike the lipids.
(CH2O)n, or if you like, more
informatively, (H-C-OH)n.
And because of the hydroxyl
group, carbohydrates are
pretty much always
hydrophilic.
The monomer of carbohydrates
is called a monosaccharide.
And there can be polymers
that are two
monomers or multiple monomers.
So the monomer--
and you should know this--
is called a monosaccharide,
where
saccharide sounds like saccharin.
That means sugar.
And there can be dimers, which
would be a small polymer,
which would be a disaccharide.
And then you can also get long
sugars, which would be
polysaccharides.
A monosaccharide, for example,
would be glucose.
A disaccharide, sucrose.
And a polysaccharide, glycogen
in animals or
cellulose in plants.
All right.
Let's look at the condensation
reaction that is responsible
for making carbohydrates.
It's a simple condensation
reaction, at
least on the board.
It requires careful
orchestration by the cell, but
on the board it's
easy to draw.
One carbohydrate plus another
carbohydrate--
I'm not going to put all the
side groups on, but you
understand there are other side
groups here or another
carbon there, giving rise to--
with the release of water.
So here is a condensation
reaction.
And this bond that forms
in carbohydrates--
I'm actually going to add the
next carbons on here, instead
of X. I apologize for erasing
here, but let's put some
carbons here rather than X
because that will be clearer.
But the bond between two
monomers is called a
glycosidic bond.
And that designates that it
is found in carbohydrates.
Carbohydrates can isomerize.
That means the same chemical
formula can change its shape,
can change the organization of
its atoms, and can isomerize
between the ring and
a linear structure.
And carbohydrates can
also be modified.
They remain hydrophilic in
general, but there are many
modifications which are rather
crucial to their function.
They can get, for example,
phosphate
groups or amino groups.
And this will change their
particular properties.
Let's look at some slides.
And then I want to tell you
about a very fascinating and
important example of
carbohydrates as an
information source.
So here's glucose as straight
chain and glucose as a ring.
If you're not familiar with
looking at chemical
structures--
I keep forgetting that
is my usual board.
But let's look at this one
because it's brighter.
If you're not familiar with
looking at chemical
structures, if you see these
dark areas in a molecule, it
means that the molecule is
coming out of the board
towards you.
So it gives a bit of
three-dimensionality to that molecule.
And here are the condensation
reactions involved in the
formation of maltose, which
is a glucose disaccharide.
And here is the glycosidic
linkage.
The atoms in carbohydrates
get particular numbers.
It is the carbon atoms that
get particular numbers.
And next lecture, that is going
to become very important
when we talk about
nucleic acids.
And here is sucrose, a dimer
of glucose and fructose.
Now, depending on the
orientation of these bonds
between the saccharides, between
the monomers, they may
or may not be able to be broken
by the enzymes, by the
chemicals in your body
that are involved
in hydrolysis reactions.
So sucroses can be broken down
pretty much by everyone.
But lactose, which is the
galactose-glucose dimer has
got a glycosidic bond which
has a particular shape.
And that particular shape is
only recognized by people who
have a molecule called
lactase--
we'll talk about this in
a couple of lectures--
which is able to break this
chemical bond here.
And if you're lactose
intolerant, the reason you get
stomach ache and so on is
because you get accumulation
of this disaccharide, and it
has side effects on your
digestive system.
All right.
So I want to tell you now about
a really fascinating
example of information as
encoded by carbohydrates.
We will have much more
to say about
carbohydrates as we go along.
But I'm going to tell you
about information--
particularly here, because
we won't talk about
it very much more.
One example of carbohydrates
giving information is in your
blood type.
So for blood type, there
are specific
carbohydrates for each.
But there is the same core set
of molecules, which is then
modified to give you the
different blood groups, to
four blood groups.
This is a representation of
the four blood groups.
They are called O,
A, B, and AB.
And you probably know
which one you are.
I am A.
One of those blood groups
is really valuable.
It's called O. And it's valuable
because anyone could
receive this blood
in a transfusion.
And anyone can because it's kind
of your basic blood type.
It contains an H group, which is
the basic sugar information
on blood cells.
And all of the other blood
groups also contains this
basic information, but they
contain other sugars as well,
here indicated by purple.
The key to these different
sugars is indicated below.
But O can be given to any kind
of person because you do not
have antibodies against this
particular H group.
Because everyone's got it.
So O is the only blood group
where, when you put it into
anyone, there are
not antibodies--
which you'll learn about
later in the course--
that will then attack the blood
cells and cause massive
blood clots and deaths.
When people donate blood, 3/4 of
it is not O. After a time,
blood is thrown away from blood
banks because it's not
usable forever.
And a lot of this type, A, B and
AB blood, is thrown away.
And so investigators have been
asking for a long time whether
they couldn't remove these extra
sugars from AB, B, and
A, and turn those bloods into
type O, which would then be
useful for everyone.
It turns out that's kind
of difficult to do.
But a few years ago, a group
did come up with
what may be a solution.
It still hasn't been proved,
even though this
was a few years ago.
It takes a long time.
Here's a different
representation of the sugars
on blood types.
Here's group A and group B.
And there are enzymes--
there you see, office hours.
I'm not kidding.
It's on my calendar.
All right.
There are substances, enzymes,
we'll talk about which can
actually remove some of these
sugars off groups A and B and
convert them into group O.
These substances, these
enzymes, were isolated
by Liu et al.
When you see this
at the bottom--
Here's a piece of education.
Often I will show you something,
and in the bottom
right-hand corner it will say
"Liu et al" or "Jones et al"
and a date.
That refers to a publication.
This group was able to convert
group type A and type B into a
type O. And they are now working
on a machine which can
convert type A, AB, and
B blood into type O.
And we'll stop there.
