Macromolecules: Lipids, Carbohydrates, Nucleic Acid, Excerpt 2 | MIT 7.01SC Fundamentals of Biology


Monomer of nucleic acids is
called a nucleotide, which I will abbreviate NTIDE. And a nucleotide comprises
three parts– a phosphate, a sugar,
and a base. Phosphate, sugar, base –that we
will abbreviate P-S-B. The polymer of nucleotides makes up
ribonucleic acid, RNA; or deoxyribonucleic acid, DNA. You need to know the full
names of those. I’m not going to
write them out. And those are all
polynucleotides. And the way that polynucleotides
are put together is through the joining
of the phosphate and sugar into a sugar phosphate
backbone, from which the bases hang. And so they look kind
of like this. There’s phosphate,
sugar, phosphate, sugar, phosphate, sugar. And from the sugar
hangs the base. The phosphate and the sugar, as
I’ve just said, forms the sugar phosphate backbone. And the bases, as we’ll discuss
in a moment, comprise the information that is encoded
in nucleic acids. Let’s talk more about this
nucleotide and the structure of the nucleotide and the kinds
of components there are in the nucleotide. The sugar of the nucleotide
is a pentose. It’s a five carbon sugar. It is called ribose,
and it’s cyclic. And it’s called ribose in RNA,
and as you will see, deoxyribose in DNA. There are four bases in DNA. They are called adenine,
guanine, cytosine, and thymine. And they are abbreviated
A, G, C, and T– by their first initial. But you need to know
the whole name. In RNA, the bases are the same, except instead of thymine– there is no thymine. Instead, there is something
called uracil, which is closely related, and
abbreviated U. The bases have a particular
structure. You do not need to be able to
draw them, but you should be able to recognize the
class of base. There is a class called
purines, which comprise two rings. I’ll show you some slides
in a moment. And adenine and guanine fall
into that category. And then, there’s another class
called pyrimidines, which are made of one ring. And cytosine, thymine, and
uracil fall into that class. Let’s draw the structure
of a nucleotide out in chemical formula. We’re not going to
draw the bases. We’re going to draw mostly the
sugar and the phosphate, because it will be important
when we think about polymerizing nucleotides. And then I’ll show
you some slides. So nucleotide structure– the best way to draw a
nucleotide structure is to start with the sugar. So start with an oxygen. And then you can put
in the carbons. And the carbons are numbered,
because, in many macromolecules, there are so
many carbons, it can be very useful to give them
specific numbers. And that’s true in the sugar. It’s also true in the bases. But the sugar numberings
of the carbons are very important for you. There’s a one prime carbon, two
prime, three prime, four prime, and five prime. The base is attached to
the one prime carbon. And the phosphate is attached
to the five prime carbon. The two prime and the three
prime carbon are also notable. The three prime carbon always
has a hydroxyl group. And it’s this hydroxyl group and
this hydroxyl group of the phosphate that react together
when the sugar phosphate backbone forms covalent bonds. The two prime carbon can either
have a hydrogen, as in DNA, or a hydroxyl as RNA. Hydroxyl groups are reactive,
and having this extra hydroxyl group on RNA makes this
sugar more reactive than the one in DNA. OK. That is your nucleotide
structure. And you should know it. Let’s see what we have
for slides here. Nucleic acid monomer
and polymer. We’re going to draw in one
moment the nucleic acid polymer on the board,
but here it is. Here is the sugar, the base,
and the phosphate group. All right. Let’s think about how you
actually get this sugar phosphate backbone formed. And let us draw formation
of a dinucleotide. And I’m going to abbreviate on
one of the nucleotides the phosphate as PO4, otherwise we
won’t fit this on the board. So let’s put the sugars first. And let me actually just make
sure that you guys understand that the sugar can be drawn as
I’ve drawn it, with all the carbons there, or it can be
drawn in this way, where the carbons are the apices, or
at the ends of a line. If this is a new you– if this
is new organic chemistry formula to you or chemical
formula to you, then please come and see one of us, and
we’ll make sure that you get up to speed, because you really
do need to know that for this course. Okay so let us draw
some sugars. Actually, I’m going to erase
this one and put it even closer to the top of the board,
because these are small boards no– new boards, nice but small. Okay. And we’re going to put here
a phosphate group. I’m going to extend this. And we’ll put a phosphate
group here. And we’re going to put a base. And we’re going to put a
three prime hydroxyl. So here is the five
prime carbon and the three prime hydroxyl. And this is going to
be nucleotide one. And then we’ll draw an identical
one below it, which will be nucleotide two,
where now I’ll draw out the phosphate. Let’s again start with the
sugar and a hydroxyl. And then let’s put
in the phosphate. Okay. And this is going to
be nucleotide two– so nucleotide one and
nucleotide two. The phosphate, hydroxyl,
and the sugar– and we can put in some
negatives here. On the phosphate, that’s fine. Depends on the pH as to what
the ionization of the phosphate group is. This hydroxyl group and
this phosphate group, are going to interact. And the outcome is going to be
a dinucleotide, where the two nucleotides, as you will see,
are joined by a particular linkage called a phosphodiester
linkage or a phosphodiester bond. We’ll leave a phosphate
there attached to the five prime carbon. Here’s the first base. And now, we’ve got– and I’ve got to fit it in. Okay. So here is our dinucleotide– slightly skewed, but OK. And there are three features
that I want to point out to you on this dinucleotide. The first is the bond that
joins them together, which is this guy. It is called a phosphodiester
bond or phosphodiester linkage. And the second is that
the two ends of this dinucleotide are different. On one end, there is a
free phosphate group. And where there is a free
phosphate group, that is called the five prime
phosphate, or the five prime end. But the five prime end
has got a phosphate. That’s part of its property. On the other end, you’ll
see, there is a free hydroxyl group. And that is called the three
prime hydroxyl, or the three prime end. And they’re equivalent,
pretty much. But you should know that at
one side, there’s a free hydroxyl group, the other side
a free phosphate group. You will see later on that
this is pivotal in synthesizing DNA, as in DNA
replication and mitosis, meiosis, and so on. All right. Few more slides– here are the sugars that are
found in nucleic acids. There’s the deoxyribose
and ribose. I just put these up
for you for recap. Here are the bases. Here are the pyrimidines– cytosine, thymine,
and uracil– and then the purines, with this interesting di-ring structure. This I drew for you, okay? And so it’s on your
PowerPoint. If you’re a bit shaky as to
what’s on the board and how we got there, you can go and get
this from the PowerPoints that I’ll post after class. All right. Now, in contrast to lipids and
carbohydrates, nucleic acids, and as you will see, proteins,
have two extraordinary properties that allow them to
encode information in really a way that is extremely rich. And those two properties I’ve
already touched on. One is that the ends
are different. They’re different in a
dinucleotide, and they’re different in a polynucleotide
that’s a thousand nucleotides long. So they have different ends. And the bases have
a linear order. And this linear order is part
and parcel of the information that the nucleic acid encodes. So let’s draw out,
for instance— and we’re going to start
with five prime. Phosphate, sugar, phosphate,
sugar, phosphate, sugar phosphate– and we’re going to end with the
sugar that has the three prime hydroxyl. Okay, so we’ve got a five prime
and a three prime end. And from this, the bases
are hanging. Now, when nucleotides are
incorporated into a nucleic acid polymer, there is an order
of synthesis, which is why the linear order of the
molecule eventually can be used for information. The base nearest the free
five prime phosphate is the first added. And the base– so it’s part of the
nucleotide– nearest the three prime hydroxyl
is the last added. It’s really important
that you know this. Furthermore, when we write out
nucleotides, nucleotide sequence, when we write out a
nucleic acid sequence, we don’t generally write the sugar
phosphate backbone in. We just write the bases. So it’s written five
prime, base, base, base, base, three prime. But of course, the bases
can be anything. So for example, we could have
five prime, adenine, guanine, guanine, cytosine,
three prime. And there’s a convention that
you have to follow. And it doesn’t matter how long
you’re in this business. When you write out a nucleic
acid polymer, you always write the five prime and the
three prime end. I’ve been in this business for
30 years now, and I still have to write the five prime and
the three prime end. If you don’t, you get lost, and
you will get mixed up in your calculations, both in this
course and in real life. Now, there are lots of
combinations of bases, even though there are only
four bases. For example, if there are four
bases and you have a three nucleotide polymer– four bases, three possibilities,
64 possibilities. Genes can be thousands and
thousands of bases in length. And so the information, the
combinatorics involved in the nucleic acid polymer
is very large. So genes can be, let’s say,
100 to ten to the fifth nucleotides long. And so the number of
possibilities is really extraordinary. And it’s one of the reasons
that all of life can be encoded in nucleic acids. And the last thing that
I want to tell you about nucleic acids– which will become and will
remain one of the most important things you learn
in this class– is that DNA is usually
double stranded. RNA is too, but it’s really
DNA that uses this in an extraordinarily important way. So DNA is usually
double stranded. What does that mean? It gets to be double
stranded via something called base pairing– you’ll see what this
means in a moment– which also means, or there’s
another term that’s used, which is complementarity,
as you will see. And this double strandedness
does not involve covalent bonds. It involves that special type
of bonds that we discussed last time, which are
the hydrogen bonds. And there are rules
about this. Adenine will form two hydrogen
bonds with thymine or uracil. Guanine forms three hydrogen
bonds with cytosine. And that is a rule that is one
of the most important rules in nucleic acids. From your book, here is a
picture of the two bases, adenine and thymine, that can
be lain opposite one another such that these dotted lines
are hydrogen bonds between oxygen and hydrogen or nitrogen
and hydrogen– and the same kind of thing
for guanine and cytosine. You don’t need to know these
structures, exactly, but you do need to know base pairing
inside, outside, and never forget it. Okay. Why is this important? I’ll tell you why this
is important. It’s important for DNA
replication and for the passage of hereditary
information from one generation to the next. So, in DNA replication, the
idea is to pass genes on, unperturbed, in the same
sequence from one generation to the next at every
cell division. So let’s just, for instance,
start with a polymer here. Ah, and something else that I
needed to tell you, which I will in a second, is that when
nucleic acids form double stranded structure, one strand
of nucleic acid– my one arm– will form a double stranded
structure with another strand of nucleic acids, like so. Okay. That’s what’s referred
to up there. The adenine’s on one polymer. The thymine is on
another polymer. When these polymers form, they
form in what’s called an anti-parallel direction. It’s really hard to do. But if this is my five prime end
and three prime end, the five prime end of one and the
will be opposite the three prime end of another strand. I guess I can do it this way– topologically easier. Okay– so five prime opposite three
prime, five prime opposite three prime. So let’s draw the complement
of this for the nucleotide polymer. There’ll be thymine, cytosine,
adenine, thymine. And look what I’ve done to the
five primes and three prime. Means they are one five prime
opposite a three prime, and the other three prime opposite
a five prime. This arrangement called an
anti-parallel arrangement of nucleic acids. And it is super important that
you never forget this. During DNA replication, the
strands of this double stranded polymer separate. And so you have five prime
AGTA three prime– is one strand– plus three prime TCAT five
prime– two single strands. And here’s the magic, and this
is what Watson and Crick got the Nobel Prize for long ago
for understanding that when DNA replicates, those strands
get filled in. So this five prime AGTA three
prime will now get synthesized opposite its complement– three prime of TCAT five
prime plus this guy– three prime TCAT five prime will
get its complement made. And look what you have got. You have started with one
strand, one double stranded moiety, and you’ve landed up
with two identical replicas of what you started with– so two identical replicates. That’s redundant, but it really
pushes the point home– two identical replicates of this
parent molecule that we started with. We’ll have a lot more to say
about this when we spend a whole lecture on DNA
replication, but you should understand that this is one of
the profound natures of DNA as the hereditary information. And from your book– double
stranded DNA. We’ll have more to say about
this, but double stranded DNA, because of chemical
considerations, goes into its most stable chemical state,
which is this very beautiful double helix that has structure
and is able to pack very tightly so that you
can get lots of genetic information in one cell. Last thing about
nucleic acids– RNA is often single stranded,
but it can also form structures that are partially
double stranded. And this is one such RNA
that’s formed this very complicated, partially double
stranded molecule.

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