Good morning. Let me also welcome you to
biology 1A and back to campus. This is
your first day of classes; I always like
this class the first day because
everybody's here and you'll notice
that today and then you'll come next
Monday and you will notice a lot of
people aren't here. I'll talk
about that. Mike has talked a lot about
the syllabus, so there isn't much more I
I want to say about the syllabus. But
please look at it, because there's useful
information in there, particularly when
the exams are and this little section on
page 3: "how to do well". I cannot stress
enough the point of keeping up with the
material in this course. We move very
quickly. I have 14 lectures and I have to
be finished by my 14th lecture
because Bob Fischer comes after me and I
I can't borrow a lecture to finish
up, so we move very quickly.
Now a lot of you, I can tell you what
you're going to do. We webcast our
lectures; they're not simulcast anymore,
but they are on the web. And if you don't
know how to look them up on the web, that
is also presumably in the syllabus, but
what students do is then they don't come
to lecture.
I understand, it's easier to watch the
webcast at 4 o'clock or 8 o'clock at
night or 10 o'clock at night and get up
at 8 o'clock in the morning but you tend
to slide back and don't watch those
lectures until the weekend before the
midterm and then all of a sudden you're
faced with 10 or 12 lectures with an
enormous amount of material and some of
you may do all right, go get through that
material and understand it. I would say
most of you don't do all right. So by not
keeping up with the material you are
building up sort of this backlog of
material that you're gonna have to deal
with. You also lose the advantage of
coming to office hours on a regular
basis and getting your questions
answered. So we think the webcasts are
great as long as they are used as an
auxilary to the
to the lecture. That is, come to lecture
and thenm if you're going over your notes
and you don't understand something
because you fell asleep during that part
of the lecture or whatever, go to the
webcast and and clarify that
material. The other thing Mike stressed
is we have office hours and
availability for you on a regular basis.
I put all my information up there. My
office address, my phone number, my email
address. I will have office hours every
Monday, Wednesday, Friday after lecture
from 9:00 to 10:00. I will also have
office hours on Tuesday and Thursday
from 9:00 to 10:00. If you can't make any
of those office hours and want to get
material covered with me, let me know.
people walk down from here to VLSB [Valley Life Sciences Building]. The
office hours are held in 2084 VLSB. After
lecture people walk down and ask me
questions. That's fine. If you see me
walking across campus and you want to
ask me questions, that's fine. I also go
to the gym, RSF [Recreational Sports Facility], every morning at 6 a.m.,
before lecture. Six to seven in
lecture days and six to little later
than seven on Tuesdays and Thursdays. I
have had students come up to me at the
gym and say I didn't understand, this
thing you were talking about protein
structure. That's fine, that's good. I mean,
believe me, I'm at the gym everyday.
The weekends too — not at six, they don't
open at six. So, it's important for you
to keep up with material and, as
Mike said, those of us who teach this
class, do it because we enjoy doing it.
I have taught it for 20 years. Nobody
makes me teach this class, I teach it
because I like the material,
I think biology is a fantastic subject
and really exciting, and I like the
students, you guys out there, so I
continue to teach this class. We like
students, believe it or not. All of us,
myself, Bob and John, we really do like
students and we like teaching students.
So this is why we're involved with this
class and we think it's a very good
class. It's a demanding class, but if you
put the effort in, you're going to do
okay. I think we we all do a good job at
trying to tell you what we expect out of
you from the lecture material. This
booklet, this green booklet, is very
important for my lectures. I cover the
material that's in those 50
or 60 or whatever number of pages. So
it's absolutely important for you to
have that booklet bring it the lecture
and I will be referring to figure 1,
figure 2, etc. down through the book, to
figure 130-something. And when it comes
to my exam, I sit down with that booklet
and I look at those figures and I create
my exam questions from the figures that
I have lectured from. So,
whatever it's called, lecture, course
reader or whatever is absolutely
important. I don't use PowerPoint, I use
the blackboard. Some of the figures that I
draw are terrible because I'm lousy. My
handwriting will never be as clear as
this, because I had some time. I do get
here early before lecture and I try to
put on this far board what I will be
covering. Another important announcement,
so if you wander in here and you want to
know what's going on today, look at this
board; it tells you we gonna talk about
molecules and macromolecules. Office
hours will start on Monday and there's
one hand out: the syllabus. I talk
fast, I'm sorry.
Any questions? You can ask questions. If I
see you, I will answer them. It's very
hard in this room to see students and
it's very hard to see when hands go up.
Yes?
No, no, those are the five subjects that I
will lecture on. There are five
different subjects and they're broken
down by these titles. Now in the
lecture handout you will notice that at the
end of each section there are what I
call study questions. These are questions
that I've [inaudible]. Some of them are trivially
simple, but they are a general review of
the topics in that particular section. I
structure my exam in this order. In other
words I'll talk about this subject,
then questions on this [inaudible] like that, and
that I think makes it a little easier
for you.
Okay. Yes? 421C. It's a little
office inside a lab. Don't be intimidated.
If you ever have to go into a lab go,
go into the lab. The first thing we like
to point out in here is on page one
of our of the exam of the lecture
readout, and that is the the chemistry
requirement. I assume you've all had
chemistry. We assume you all have
chemistry. Yes? I don't think we've we've,
nom we've never used iClickers. I
protest against iClickers. I don't know
why. Maybe someday somebody will want to
try it, but I'm not going to do that. Okay,
the chemistry requirement is clear. What
we expect you to know in a general way
is shown on that first figure. For my
part what I expect you to know is
something about ionization, what that
means, something about bond strength, what
that means... More importantly the
functional group or functional groups in
organic compounds. We're going to be
talking about basically organic
chemistry: sugars, amino acids, nucleic
acids, and you have to know when I
say it what an alcohol is and what
an aldehyde is and what is
ester is. We don't spend any time giving
you the background of organic chemistry.
Later on in the last portion of
my lectures on these two subjects we will
be talking about oxidation-reduction
processes generating energy, and if you
aren't familiar with oxidation-reduction,
that's going to be difficult. Another thing
we talk about which is very important
is phosphate and phosphate bonds. So
things like that which are summarized on
page 1 are pretty important. So. as I
said, the first subject that I talk
about is biological molecules, and if you
look at all living organisms,
interestingly the composition of these
organisms in terms of what you find in a
bacterium, a plant cell, an animal cell, is
very similar. And that's shown on Figure
2. That's a pie, a pie shape figure. And the
interesting feature of the pie shape
figure to the left (I can draw this one
for you, because I can draw a circle).
Essentially 3/4 of this is water, so if
you look at any living organism, it is
primarily composed of water. And this is
of course when they send probes on to
Mars or the Moon, the the first thing
they're looking for is water because the
belief is that there's no life living
organism that will exist
in the absence of water. So, if there's no
water on the Moon, there's no life-forms
as we know them on the Moon. Same for
Mars. The rest of this pie shape is
primarily biological macromolecules.
About, I don't know this is 75%
roughly. This may be another 20%
which would be biological macromolecules.
and then the rest, some five or ten
percent, are small metabolites or their
ions and things like that. Since we are
primarily water, I think it's worth me
spending five or ten minutes talking
about water and using this to introduce
a couple of subjects that will be
important when we talk about the
structure of molecules. Water
appears to be a very simple molecule, H2O.
So you've got oxygen and two hydrogens.
The interesting feature of water is it's
a molecule that has a polarity. This end
of the molecule has a partial negative
charge. This end of the molecule has a
partial positive charge, the hydrogen's.
And what this allows water to do is to
form basically a linear structure.
Water in solution is structured in terms
of hydrogen bonds between oxygen and
hydrogen, and this is shown better in
Figure 3a than I could draw it on the
board. Hydrogen bonds would be something
like this, with a hydrogen here and you
know it goes on and on. So that water in
solution is not just an individual water
molecule, but it's this lattice of water
molecules that are interacting through
hydrogen bonds. Hydrogen bonds are weak
bonds. The strength of hydrogen bonds are
approximately 1 to 5 kilocalories per
mole and this contrasts with covalent
bonds,
which are approximately 100 kilocalories
per mole. 20 times stronger. So these are
weak bonds and it's important, you'll see,
that hydrogen bonds play an important
role in the structure of proteins and
the structure of nucleic acids. And
particularly within proteins, enzyme
structure is very important, it is very
critical.
It critically uses hydrogen bonds. The
reason these bonds are important is
they're weak and they can be broken and
reformed relatively easily. This lattice
structure that exists for water in
solution gives water a lot of
very unusual properties, most of which I
won't talk about. Those of you who have
had — how many people have had bio 1B? Fair
number. Well, I know Lou Feldman
spends a lot of time talking about how
the water gets from the bottom of the
tree to the top of the tree. Right? That's
because of hydrogen bonds.
The feature that of this structure that
I want to talk about is the interaction
of water with other molecules and that's
shown in Figure 3C on page three.
Molecules that can hydrogen bond or
interact with the charges of the water
molecule, such as ions. Ions are charged
species. If you've got this structure, this is
positive and this is negative. If you
have another positive species, an ion
for example, a sodium ion I
guess is shown in the figure. Sodium
chloride is being shown. That is soluble
in water because it can interact through
hydrogen bonding or ionic bonding with
the polar water molecule. Molecules that
readily dissolve in water are known as
hydrophilic molecules,
which means water-loving molecules. So in
biological systems, ions — sodium chloride,
magnesium, potassium, iron — all of these
things are highly soluble in water
because they are charged. There are other
kinds of molecules — organic molecules —
that contain hydroxide groups (—OHs), sugars
for example — as we'll talk about probably
on Monday — they are easily dissolved in
water, again because of the interaction
of polar regions in the molecule with
the water molecule. There are however
some types of molecules that are not
very soluble in water. Those of you who
make salad dressing using oil and the
vinegar (acetic acid) know oil and water
don't mix. Oil and water don't mix
because the oil molecules are highly
insoluble in water. They don't have any
polar groups. Try to dissolve benzene in
water: it doesn't dissolve. You get two
layers. Molecules that don't dissolve in
water are known as hydrophobic —
water-hating I guess — and it turns out
that there are a group of molecules in
biological systems that are relatively
insoluble in water. So, all of a cell is
not soluble in water. There are for
example membranes, which are little
barriers around the cell and within the
cell, which are made of hydrophobic
substances and prevent water and other
charged molecules from crossing that
membrane. So you've got two classes of
interaction with water —molecules that
are readily soluble in water and molecules
that are really insoluble in
water —
both of these are found in biological
systems. We'll talk about these
molecules in much more detail over the
course of next week.
Now when you look at this pie — such pie
shaped figure — and you remove the water
and you look at what's left in this
circle, that is what's
the nature of the biological
molecules and what are the components
that we talk about in terms of
biological molecules, you can see this
again in Figure 2 that (oh, this time I
guess it's like this) some 60% to 70%
of the biological molecules are
made of proteins. Clearly the largest
component in a biological cell is the
protein various proteins then there are
sort of three other compounds: there are
lipids, there are carbohydrates and there
are nucleic acids representing the
remaining 30% or so, I think. You can see
the importance of proteins in terms of
cells and cell function by this very
simple representation of what one finds
in living organisms. I'm going to start
talking about proteins today and I spend
a lot of time on proteins for a variety
of reasons. One is, proteins are the
largest cellular component other than
water. Secondly, proteins play an enormous
variety of functions roles in a cell and
I think proteins are the most
interesting macromolecule (large
molecule) in the cell. I've worked for, you
know, 40 years or more on proteins.
Proteins, various protein structures and
function. So proteins are pretty
important. You'll hear much more about
nucleic acids in the second portion of
this
class when Bob Fischer lectures, so I
don't talk that much about nucleic acids.
If you look at figure 4, it shows
something important about the kinds of
molecules that are found in cells. These
molecules are in general — they are
macromolecules — we call them
macromolecules being large molecular
weight components. And this one, this one
and this one — I can even put them in
the boxes — are generally found as
high molecular weight polymers, which are
built up from lower molecular weight
individual units. That's what's shown in
figure 4.
So sugars or carbohydrates are
polymerized through the addition of
sugar individual sugar units to form
polysaccharides. Amino acids are the
building unit of protein, so one takes an
amino acid or a number of amino acids
and puts them together to make a protein.
One takes a nucleotide and puts a number
of those together to make a new nucleic
acid. The monomeric unit is different:
in this case it's a monosaccharide, in
this case it's a nucleotide, in this case
it's an amino acid. Now I've left lipids
out of this, because lipids are a little
different. Lipids don't form high
molecular weight polymers, although they
form something which is bigger than the
individual components. For example in a
fatty acid one has a glycerol molecule
and a carboxylic acid — and we'll talk
about that — but there are no high
molecular weight polymers that are
formed in relation to lipids. The kind of
bonds that are built up as you make
these polymers varies and we'll talk
about that in much more detail.
Some of the types of molecules
are summarized in Table 5. Table 5
is kind of a useful table. Here's an
examplem and I'll keep making this point
over and over. You should look at
this table and you know — don't memorize
it. I cannot emphasize enough to you.
Please don't memorize very large
complicated tables. Do not memorize
chemical structures. We're gonna go to a
figure very quickly on the next page, on
page five, where all of the amino acid
structures are given. I don't want you to
memorize those structures. I'll tell you
what I do want you to know. Later on
we're gonna be dealing with the
structure of DNA and RNA nucleic acids;
it's the same thing. I don't expect you to
memorize all of the bases that are
forming DNA and RNA. There are some
things you have to know, there's some
things you have to understand, but you
don't have to memorize these structures.
You're all gonna take MCB 102 or MCB 100,
which is the basic biochemistry –
molecular biology course. You'll have
ample opportunity to memorize chemical
structures there. If it's the same as it
used to be. An example of what we're
doing when we're making these polymers
amino acids: have a molecular weight of
about a hundred daltons, okay? If you take
50 amino acids,
you will make a protein that has a
molecular weight of 5000. If you take 500
amino acids you will have a protein that
has a molecular weight of 50,000.
There's no average weight molecular
weight for a protein, but it's not
unusual to find proteins with masses of
50,000 to 100,000 or larger. So what
you're doing is you're taking a large
number of amino acids and putting them
together to make a protein. Now the
question that often comes up is "how many
amino acids does it take before you call
it a protein?" Depends who you're talking
to. Probably 5.000 Da would be, you
know... 50 amino acids or something,
people will start to call that thing a
protein. Below that they give it a
different name, but there's no
rhyme nor reason to say: "the cutoff
point for calling some polymer a
protein is 3800 or 4000 or 5000". Then that
doesn't exist. When we synthesize these
polymers, fortunately for you it's very
simple. If you look at figure 5 it
shows how two monomeric units, in this
case sugar molecules, are being condensed
to form a disaccharide. The sugar units
are monosaccharides; they react together;
water is split out and a disaccharide is
formed. In this case — I'll put this on the
board. So proteins contain amino acids
and these amino acids are linked by
peptide bonds. And we'll go through this
in more detail. Polysaccharides, which are
the polymers of carbohydrates, contain
monosaccharides
and the bonding are glycosidic bonds.
If you can't read what I
write, if you can't hear what I say,
you're gonna have to yell and scream,
okay? And nucleic acids. The units here
are nucleotides and the bonding is
called phosphodiester bonds. So this
is sort of — and then we've got the
lipids, which I'm just gonna leave open
here and open here, because they're
they're different enough so that we
don't include them in this table. So in
each of these cases one is taking a
single unit such as a nucleotide or a
monosaccharide an amino acid, condensing
it with another amino acid,
monosaccharide or nucleotide, splitting out
water and synthesizing. In this case it's
the dimer and then you continue doing
this until you get a high molecular
weight polysaccharide. The synthesis of
these compounds requires energy. The
reaction is reversible as it's shown in
that figure 5. You can break down
these compounds, these high molecular
weight compounds. If the synthesis
requires energy,
the breakdown releases energy. For
example when we digest sugars or
proteins, we are releasing energy to
ourselves that can be used for the
synthesis of other molecules and
materials. So there's this synthesis and
degradation that occurs in all
biological systems. OK, in the next five
or ten minutes — oh, the other thing I
have to mention, this is important: at
nine o'clock this stage rotates. Do you
know that? You ever seen it rotate? And
the chemists comes
streaming in. There's chem 1A, follows
this. And they are unforgiving. They'll
trample you know, run you over. So I have
to get off the stage, otherwise I
disappear in the back. So I can't linger
around on the stage very long, so if I'm
a little short with you you know why.
Because the chemists are... they're much
more aggressive than the biologists. The
first year I taught this
course, there was a professor who
followed me and he gave me a lecture — the
first lecture — he lectured me. He said: "you
have to be off of that stage at nine
o'clock, cause we have to start." The
chemistry people are in the back. Their
setting up the material for their
lectures, they do a lot of demonstrations.
Do not be afraid if you hear an
explosion. Every now and then there's you
hear a boom and somebody will appear at
the door and say it's alright. Don't
worry about, but they're back there, this
is a threeway stage so they're back
there setting up for the chemistry.
What I'm going to talk about is proteins
and as I said, I think proteins are
really neat, okay?
The basic unit when we talk about
proteins is the amino acid. And an amino
acid looks like this — it's got an amino
group, it's got a central carbon which
has a hydrogen on it, it's got a carboxyl
group and it has an R group, it has a
sidechain. And what makes amino acids
different is the nature of the R group.
So every amino acid has an amino group, a
carboxyl group and an R-group. I've
always included this little figure,
Figure 7, because it comes back later
to sort of haunt us. Clearly if I've got
an amino group and a carboxyl group.
This for example carboxyl, depending on
the pH, can lose a proton. This is a pH it
can ionize.
And it shows you, Figure 7, at various
pHS what form of the amino acid exists.
Besides the carboxyl and the amino group
can gain a proton and become
positively charged. Some of the side
chains that we're going to talk about
can also lose or gain protons. That has
become positively charged or neutral. And
this turns out to be very important in
the structure of proteins and the
structure and function of enzymes which
we will talk about in great detail. So
you should be aware that you can ionize
the carboxyl, ionize the amino group and
ionize some of the side chains that have
for example carboxyl groups in them and
that may come into play when we talk
about the structure of proteins. Okay.
There are in proteins — I don't know if
this is good or bad — there are twenty
amino acids, twenty different amino acids,
that are found in proteins. Now there are
probably thousands of amino acids that
exist out there in the world, but only
twenty amino acids are found in proteins.
Not all twenty are found in any one
protein, some have missing several, but
the maximum number of different amino
acids that you will find in a protein is
twenty. So I suppose that's good because
ultimately you only have to learn twenty
structures, okay. The amino acids are
grouped together based on the properties
of this R-group sidechain. So you can see —
this is why you have to
have this book okay, you look at the top
of that Figure 20 and it says amino
acids with electrically charged
hydrophilic side chains. I've told you
what hydrophilic means — hydrophilic means
they are going to interact strongly with
water — so you might expect those side
chains to have positive charges or
negative charges.
And if you look through these compounds,
you can see there some of them have
positive charges, because they have an
amino group in this R, okay. So you may
have something — it goes up up up up — and
then there's an NH2 that can be
positively charged. Then there is also a
series of amino acid side chains which
are negatively charged: glutamic acid and
aspartic acid. They do not contain this,
but they will have an R-group that has
a carboxyl group on it, and that carboxyl
can be ionized, so these side
chains have the capacity to have a
charge in them. Then there are a series
of amino acid side chains which don't
have charged groups but they may have
OHs or they may have SHs. And these are
still hydrophilic, because these are
electron rich compounds and they can
bond very strongly with water. The
classic example is serine, the amino acid
side chain serine, this is the R-group in
serine, okay, CH2OH. That is shown, yeah.
Let's give you the right structure.
Okay, that's the serine R-group. So that
oxygen makes this a very hydrophilic
side chain. We'll deal with special cases
in a minute. Then there are a number of
amino acid side chains which are what we
would call nonpolar, and we would also
now use the term hydrophobic. These are
amino acid side chains that have no
charges,
they have no oxygens they have no
sulfurs. They're basically hydrocarbon-like.
The best one to look at is
something like isoleucine or leucine
where you have just carbon atoms, okay? So
that's a side chain that is not
going to interact very well with water.
There are also some, what we call special
cases. The most important one that I want
to talk about is the amino acid side
chain cysteine, which has a CH2—SH. Its
side chain has a sulfur. This sulfur can
react with another sulfur in another
cysteine. And what would have is this and
you can remove these hydrogens and you
get this thing you get a sulfur sulfur
bond. This amino acid is known as
this is cystine, okay. And we'll talk
more about this kind of structure in
molecular structure of proteins. They're
very important, so the others are not all
that important. What I want you to
appreciate in terms of the structure of
amino acids is how these things are
grouped. What are the features, what's the
basis of putting an amino acid in say,
the hydrophilic side chain group or the
hydrophobic side chain group. And then after
we talk more about protein structure, I
want you to be able to appreciate how
these amino acid side chains are going
to organize themselves within the
protein, because when proteins are formed
they form a three-dimensional structure
that is essential to their activity. And
to form that three-dimensional structure,
there's interactions of side chains of
amino acids. Okay, last thing. If you look
at Figure 9, Figure 9 shows how you make
a peptide. That is, you take amino acid 1,
AA1, and AA2. In this case it's a
glycine and an alanine, and the carboxyl
group on one amino acid reacts with the
amino group on the other amino acid. So
I'm just going to abbreviate this.
R1, R2, I'm just drawing what's in
the — ok. So what you do is you split off,
you split off water, H2O, okay? That's this
condensation reaction. Water is split off
and the structure that's formed, which I
won't put on the board here, is a peptide
bond, where one amino acid is linked to a
second amino acid. On one end you've got
an amino group, which is still free, on
the other end you've got a carboxyl
group, which is still free. Wvery protein
has an amino end, which is called the
N-terminal end, and a carboxyl end, which
is called the C-terminal end. So there's
always a free end here and a free end
here. This carboxyl will react with
another amino group in another amino
acid to build this polymer up until you
have some you know 500 amino acids which
becomes a protein. OK, I think this is a
fine place to stop
and on Monday we're gonna continue, I'm
going to talk about what happens when
you have this protein built up and how
does it obtain its real structure.
