ORIGINS OF LIFE - CHEMICAL ORIGINS
MACROMOLECULES SUGARS AND NUCLEIC ACIDS
Hi, I'm Sarah Maurer, and in this lecture
we're going to talk about sugars and nucleic acids,
two of the four macromolecules that make up your cells.
Sugars are really important because they are used for generating
and storing biological energy.
In the figure, you can see that carbon dioxide
is turned into glucose through photosynthesis
in plants and some algae.
And, that sugar is then stored until we are ready to use it
to generate ATP through respiration,
which we then exhale the carbon and the oxygen from our lungs.
And, sugars can be used for a lot of other tasks in multicellular organisms,
and even single cells, such as molecular recognition,
and cellular protection, such as a peptidoglycan layer.
But they are also used as an integral part
of the macromolecule RNA and DNA.
Sugars have a huge variety of structure.
And so, here you can see that, when we have a 3-carbon sugar,
there is only one possible structure.
But, when we get down to having a 6-carbon sugar,
there are many possible structures that all have distinct chemical properties.
And, when we talk about sugars, we talk about the sugars being D-sugars.
D-sugars have the second to last carbon with that OH group on the right hand side.
And so, you can see in every layer of this:
the second to last carbon has an OH group on the right.
The other carbons, which can have the OH group
on either the right or the left, have every possible variation of this
to make up our composition of possible sugars.
The most common one that you probably recognize in this group is glucose,
the 6-carbon sugar.
And, when we name sugars "aldose", what we are referring to
is that the first carbon in the sugar has a doubly-bonded oxygen,
called an "aldehyde".
There is a second type of sugar that has the doubly-bonded carbon
on the second carbon,
and that is called a "ketose" or a "ketone sugar".
In ketoses, because there are less carbons that have two sides,
we have less variation.
But, you still end up with the second to last carbon having a "hydroxyl" group,
or an OH-group, on the right hand side, making it a D-sugar.
The ketose that you are probably the most familiar with is fructose,
which is shown in the 6-carbon sugar, the hexose.
These sugars are not always linear,
in fact, they are very infrequently linear in the body.
So, ribose in the body is only in its linear form about 0.9% of the time.
The rest of the time, it either folds up into a 6-membered ring
or into a 5-membered ring.
The 6-membered rings are called "pyrans"
and the 5-membered rings are called "furans".
So, this gives... one 6-carbon sugar
four additional forms, right?
So, sugars can have a huge diversity of structure,
which allows them to have a large amount of function
or a large diversity of function.
The other really important part of the structure of sugar
is whether or not the reactive OH group is on the bottom of the sugar
or on the top of the sugar.
Here, the reactive OH group is shown in green
and it is called the "anomeric" oxygen.
The anomeric oxygen is from either the aldehyde or the ketone,
the top of our sugar - our linear sugar.
And, it can either - depending on how the bond opens -
it can either end up on the bottom of the sugar,
which we would call an "alpha" sugar,
or it ends up on the top of the sugar, which we call a "beta" sugar.
Because the anomeric oxygen is the reactive oxygen,
this is where sugars are going to polymerize,
this is where we are going to add functionality to the sugar.
So, this is really important in making polymeric sugars,
which exist in your body for storage, like amylose or starch,
which you find in potatoes,
or cellulose, which you find in the structural sugars of plants.
The additional reason that this is really important
is because ribose makes a part of our DNA and RNA,
and the type of ribose that is in our DNA or RNA
is the beta furanose form of ribose, which you can see
is not the most abundant naturally- forming ribose cyclic sugar.
And so, we need enzymes to help us to make ribose
into that beta furanose form.
Sugars can be made prebiotically
through what is called the "formose" reaction.
It is called the formose reaction,
because we take these small, organic formaldehydes
and we react them together to make larger and larger carbon units.
So, formaldehyde was possible on Early Earth
through the reaction of carbon dioxide or carbon monoxide with hydrogen gas.
And, by reacting these together in water, you end up with
larger and larger sugar chains, 5-carbon or 6-carbon sugars.
And, this process, if you let it react further,
will turn into something that looks like tar -
kind of what you would end up with if you overcooked your caramel.
Once we have synthesized our 5- and 6- carbon sugars on Early Earth,
then we can start to build nucleic acids, which are a second type of macromolecule.
To make a nucleic acid, you first need to have a "nucleobase".
And, these are called "bases" because they contain nitrogen and carbon.
The nitrogen is what makes these basic.
There are two types of bases, "purines" and "pyrimidines".
Purines have a 6-membered ring, linked to a 5-membered ring,
and they are composed of adenine and guanine - the A and the G base.
Pyrimidines are the cytosine (C), thymine (T) and the uracil (U) base,
and they are a single, 6-membered ring.
Uracil is only found in RNA and thymine is only found in DNA.
These nucleobases can base pair to form specific recognition.
The adenine, or the "A base" base pairs, what we call "Watson and Crick"
base pairs with the T base, forming the A-T pair.
This has two hydrogen bonds, which is shown here
by the dotted line between the A and the T.
And this is a non-covalent bond, it is not as strong as an actual bond,
but it serves so that the bases can come together
and then also be pulled apart if they need to be copied.
In the G-C pair, you can see that we have three of these hydrogen bonds,
which makes the G-C base pairing stronger.
To make these bases in a prebiotic setting is a little bit challenging.
In this synthesis, you can see that we start in the center
with a methane, a CH4, and a nitrogen, N2.
This methane and nitrogen can condense together
to either form a cyanide or a larger carbo-nitrogen complex,
which then goes through subsequent rounds of reaction to form our final bases,
which are highlighted in the periphery in this yellow color.
And, you can see that
there are several ways to make each base,
So, uracil, for example, pops out on a couple of different places.
And so we can use a variety of different environments
to actually synthesize these bases,
depending on the location that we really want for the origins of life.
Once we have the bases, we can add them to our ribose,
which we made through our formose reaction.
The bases here are shown in grey
and they are added to the first carbon of our ribose.
Now remember that's our reactive end of our ribose,
and that is normally where we would have an OH group,
but the OH group leaves and the carbon then binds
to one of the nitrogens on our bases.
The ribose, if it is in RNA, has an OH group on the second carbon.
RNA stands for "ribonucleic acid."
If we have DNA, we are actually going to lose that OH group
and make it a deoxyribonucleic acid.
And so you can see here,
the structure on the right has lost that OH group.
That OH group is really important for forming hydrogen bonds,
which gives RNA a much more complex structural and functional possibility.
DNA is then used predominantly for information storage.
And then, you can see that the final carbon on our ribose
has a phosphate group attached to it.
And, this phosphate-sugar pairing
is going to be what makes up the backbone of our nucleic acids... polymers.
And so, in nucleic acid polymers, we will have a phosphate,
and then a sugar, and then a phosphate, and then a sugar as our backbone,
and then, the bases will decorate the outside of our nucleic acid.
That allows for the bases to come together
and form the Watson and Crick base pair throughout the nucleic acid.
When we are forming these polymers, you can do this one of two ways:
the prebiotic way would be to take the nucleotide
and to dry it down with other nucleotides,
and you get this condensation reaction,
much like we see with peptides and lipids
to produce a larger macromolecule.
So, we drive off the water through dehydration.
and we end up with a polypeptide or a multiple nucleotide unit.
The way that our body does this is, it takes ATP,
or it takes a triphosphate, instead of a single phosphate.
That triphosphate bond is high energy bond,
and so, when you break it, it actually drives the reaction forward
without needing to dehydrate the sample.
And so, the energy comes from the phosphate bond breakage,
instead of through thermal and dehydrating energy.
So, when that phosphate bond breaks, we end up with a linkage
between our ribose and our phosphate on our second molecule.
And that creates our polymeric structure of nucleic acids.
Once we have all of our biomolecules,
we have nucleic acids from our prebiotic soup,
we have lipids in our prebiotic soup, we have proteins in our prebiotic soup,
and then, we have some sugars in our prebiotic soup.
We can mix these all together, just like we see in the living system,
the biomolecules in the same ratios.
We can put in some energy, we can shake it, we can heat it,
and we still cannot create life.
And so, that leads to the question: What are we missing?