And Then Came The Polymers

What are the polymers? Well, this is a huge family of substances, and they can be synthetic or natural.

The term “polymer” derives from the Greek words “polys” (many, much) and “meros” (part). Thus, each part, or unit, is called “monomer” (as “monos” is “one” in Greek). So a polymer is made by monomers, but, what this exactly mean? A polymer can be described as a chain formed by monomers, being each monomer a subunit that is repeated all along the chain. For example, polyethylene consists of subunits of ethylene (C₂H₂) repeated one after the other. It sounds quite logical, don’t you think?

Now why would I like to talk today about polymers? Because I wanted to talk about the polymers that are present in life forms. As biochemistry is the chemistry of life, these natural polymers are called biopolymers. There are three main types of biopolymers: polysaccharides, polypeptides (a.k.a. proteins) and polynucleotides.

Let’s start with the polysaccharides, then. Under this seemingly strange name we find something we are indeed quite familiar with: sugars (here I am using the general term sugars for the whole family of saccharides; when I refer to the sugar everybody knows I will use it in singular, just “sugar”). Actually, the “-saccharide” ending comes from the Greek “sacchar”, which means sugar. Another term used for polysaccharides is carbohydrates.

Glucose, a famous member of the family of sugars, is a monosaccharide. Other examples of monosaccharides are fructose and galactose. There are many different monosaccharides. What happens if two monosaccharides get chemically bound to each other? Then we get a disaccharide. Examples: sucrose, or saccharose (made of glucose and fructose) and lactose (made of galactose and glucose). So what is a polysaccharide, then? I would define it as a ramified (non-linear) chain of monosaccharides of a rather significant length. A polysaccharide may have between 200 and 2500 monosaccharides joined one after the other!

And what is their role? Well, they can have many different functions. For example, starch and glycogen are energy storage polysaccharides (glycogen means “generates glucose” so you can guess what is it made of… yes, glucose units linked together one after the other!). Polysaccharides can also be structural, like the cellulose in plants and the chitin forming the shield (exoskeleton) of some insects.

They can also have more than one function at the same time, like hyaluronic acid (a.k.a., HA). This HA, even with its “acid” name which would sound as a not nice thing, is very important. It is able to retain a lot of water molecules so it provides moisture (and remember that we humans NEED water), but it also acts as a lubricant between cells, it is an important component of the cartilage, and it is involved in skin repair, movement and proliferation of cells, and plays a role in innate immunity. It has even been suggested it plays an important role in brain development! Another example of a multi-functional polysaccharide is the beta-glucan: it activates the immune system, and it reduces the concentration of cholesterol in blood (so if in the supermarket you find “beta-glucan-rich” cookies, you know where the interest on buying them may lie).

Before I move on to the second group of biopolymers, I would like to make a point on the relevance of glucose. This is just a monosaccharide, but it is a very important one. To mention a powerful example, when we eat anything with sugar and the sucrose is converted in our body into the separate components (glucose and fructose), we are getting the only nutrient, glucose, from which the brain gets its energy… exclusively!! (Only in certain “desperate situations” does the brain use other substances to obtain energy). Of course we need a balance of how much glucose do we intake, so please be moderate about eating sweet things!

But here is a curious thing about the glucose: it is so much important, known and famous that a lot of biochemical substances related to it derive their name from “gluco-“ or “glyco-“. For example, the aforementioned beta-glucan, or proteins which incorporate polysaccharydes into their structure (yes, this happens!) that are named glycoproteins, and if they incorporate many sugar chains then they are called proteoglycans. Even the chemical bond between monosaccharides is called glycosidic bond!!

Now let’s go on with the polypeptides. Or proteins, which is a much simpler word. In this case, the subunits that form them are the amino acids. Again, we find the “acid” word on the name, and again, our cells live with it. But where does this “amino” come from? Well, you might remember the unpleasant smell of ammonia (NH₃). And yes, the amino acids contain nitrogen (the amine group is –NH₂). Actually, in this case the amine group has a basic character which counteracts the acidic character of the other side of each amino acid. (Please remember that an acid gives a low pH and a base gives a high pH, and that the normal physiological pH is 7.4).

As opposed to monosaccharides, for which there are many of them, there are only 20 amino acids that form the proteins. Apart from that list, there are a few more that we can find in nature, but those 20 are extremely important.

The chemical union between different amino acids is called peptidic bond, and a relatively short chain of amino acids, smaller than a true protein, is called a peptide. Where does the difference between peptide and protein lie? Well, in general a peptide can consist of up to 50 amino acids, while a protein is much larger (it is made of one or more polypeptides arranged in a biologically functional way). The order in which these amino acids are linked is the sequence, and this sequence determines not only the structure but also the function of the peptide or the protein.

Again, proteins can have many functions. If the DNA is the “instructions manual” of the cells, proteins are the “machinery” that DOES the work. And like in a manufacturing plant, the shape determines the function of the protein (if the three-dimensional structure of the protein has a mistake, it will not work properly). There are proteins meant to stay inside the cells, proteins meant to go to the cell membrane and stay there (the transmembrane proteins), and proteins meant to go outside the cell (extracellular proteins, like the collagen).

An interesting example of a transmembrane protein function is the receptor of insulin. Insulin is a peptide hormone which regulates the content of glucose in blood, as its excess would be toxic. So how does it do that? The peptide is “recognised” by a receptor, so they specifically interact like a key is able to unlock its corresponding door. This triggers a signal inside the cell to uptake glucose (by another transmembrane protein which binds glucose and then makes a kind of tunnel -called channel- so glucose ends inside the cell), and the same signal activates the storage of glucose into the polysaccharide glycogen, the glycolysis (the obtention of energy from glucose metabolism) and further storage of energy in form of fat (fatty acids).

A lot of processes in our body are regulated in such a way (with biochemical messengers being “captured” by receptors which then instruct the cells to activate this and/or deactivate that). It is just amazing that with only 20 amino acids there are so many different proteins with so many different functions, and also so many small peptides, each one capable of a specific role as a messenger for certain functions (immune system, cell division, cell movement, etc).

There are even proteins which help other proteins to achieve their correct three-dimensional structure!! And proteins in charge of destroying the proteins which are too damaged to do their job!! And all this with only 20 amino acids!!!

And then we get to the last group I mentioned before: the polynucleotides. This might be the most difficult to explain but I think it is also a very exciting group of biopolymers. First, to understand what a nucleotide is we have to imagine a molecule consisting in three parts, being the central one a monosaccharide. The two famous polynucleotides are the DNA and the RNA, and in these names the D and the R stand for the monosaccharide name: deoxyribose and ribose. DNA means “deoxyribonucleic acid”, and RNA means “ribonucleic acid”. And just to satisfy the eventual curiosity of some readers, the “nucleic” part of these names comes from the place in the cell where we normally will find them (the mRNA -we will see later what it exactly is- is, at least when referring to the RNA, sythesized there): the nucleus. Again and for the third time in this article, the “A” stands for “acid”, but polynucleotides are, as you may imagine by now, very important and our cells don’t have any problem with these “acids” running around. (Anecdotically, I can also mention that a famous vitamin, the vitamin C, is also known as ascorbic acid, and you may as well remember I mentioned earlier in this post the fatty acids, so there are plenty of examples of acids we don’t only live with but also live from).

So back to the definition of a nucleotide: we have a monosaccharide (deoxyribose, D, or ribose, R), with a nitrogenous base bound on one side and one phosphate group bound on the other end. These phosphate groups are what give DNA and RNA their “acid” character. So here we have two strange things around a sugar (here I mean the general term for saccharides). And today I don’t want to mess around with chemical structures, but as their names indicate, the phosphates contain phosphorus and the nitrogenous bases contain nitrogen. It might not be of much help now, but this is just to give an idea of what they are made of. Nevertheless, these nitrogenous bases are better known by their one-letter-nicknames: in DNA, we have A, T, C and G; and in RNA we have A, U, C and G. I know, DNA is very famous, while RNA is like the hidden brother very few have ever heard of, so A, T, C and G are letters many have seen, but what’s that U in the RNA?? I beg you a bit of patience, we will get there later…

So again, in order not to lose track: a sugar, D or R, a phosphate on one side, and one of these A, C, T, G… on the other. So how does the DNA form its well-known 3D structure? Rather easy! The phosphates bind the sugars one after the other, so we get the sequence phosphate-sugar-phosphate-sugar-phosphate-sugar-…, and the bases (A, C, T, G) get exposed to the side. And, complementarily, there is another chain going the other sense (antiparallel), doing the same arrangement. And most amazingly, each chain exposes its bases complementarily: every A matches a T and every G matches a C. And then comes the real magic: this antiparallel arrangement would look like a wooden ladder, but the nature of this structure makes it twist so it is more similar to a spiral staircase. That’s it! Voilà! Double helix formed!

The RNA gets arranged in a single chain (single-stranded), but there is a trick on the way it works so even when it is less spectacular than the DNA it is still crucial. In our DNA we have all the instructions, which means we humans have around 20000 protein-coding genes spread though the length of our genome (three billion DNA base pairs!!!).

But even when it is quite convenient to store all that information in the double helix inside the nucleus, there is not enough room so the DNA is usually coiled and condensed. Which means that, if a particular cell needs to produce a protein for a needed function, first we need machinery to identify where on Earth the coding gene is located, and unfold that section of the genome. And then, and only then, the cell machinery in charge of producing that protein will be able to start the process.

So to make things easier, from the double-stranded DNA segment, first a single-stranded RNA molecule is produced. This much smaller RNA chain (called messenger RNA, or mRNA) contains the necessary information for producing the protein so the DNA can be coiled and condensed once more in order to save space again. This process is called transcription. And here is where the T from DNA gets transcribed into an A in the RNA, but an A in the DNA becomes a U in the RNA. So the transcription consists in synthesizing the complementary mRNA chain to what’s written in the DNA sequence. Then why U instead of T in the RNA? Well, we might just blame it on the evolution process. RNA was first and DNA came later, and while U and T are very similar molecules, in biology a small difference in the chemical structure means a lot, and there are advantages and disadvantages on both T and U but after millions of years of evolution it seems it is OK to leave U in the RNA and T in the DNA. Not much of an explanation, but I am fine with that.

After the transcription, the mRNA can be sent out of the nucleus where it will be translated into a protein. In this process, there is another type of RNA, called transfer RNA, or tRNA, involved in the translation itself. This translation is the synthesis of a protein. And what does the tRNA do? It recognises a sequence of three bases from the RNA (which came from a complementary triplet in the DNA) and is capable to bring the corresponding amino acid. This means that from a code of 4 letters (A, C, T and G) we go to another code of similar letters (RNA has A, U, C and G), and from groups of three of these RNA bases we can translate to the 20 amino acids. This is the famous genetic code. There are synonyms, of course (if you know statistics, you may have realized that there are more than one base triplet that can encode for the same amino acid). And there are groups corresponding for the START and for the STOP messages.

So if a cell needs to produce collagen, for example, first there will be a messenger (generally it will be a peptide, a protein or a glycoprotein) being recognized by a specific receptor (typically, it will be a transmembrane protein or glycoprotein) which will trigger the signal which will then activate the gene expression (the process of transcription from DNA into mRNA, and afterwards the translation from mRNA to protein). After the protein synthesis, and back to the example of collagen, the synthesized collagen will be transported outside of the cell, as this protein is mainly structural for the medium outside of the cells (the extracellular matrix -ECM-, where collagen will also meet HA, a polysaccharide also present in the ECM). The biochemical machinery of the cell in action!

You see, we are made of polymers which have different functions and interact with each other. And as I said in a previous article, if life started with amino acids and proteins, one of the big mysteries is how come the information of proteins ended up stored in the DNA, with the intermediary RNA-phase in between. We know this has advantages, but not how it actually happened within the evolution (unless I have missed a very important advance in this direction I did not hear of).

We know that, like in programming we have the binary code of zeros and ones to encrypt the “words” of the software, it looks quite clever to encrypt 20 amino acids in only four nitrogenous bases (or nucleobases), and that in terms of space it is clever to coil the double helix into a smaller space so from that archive the cell machinery can access determined “files” (the genes) at precise moments, but the big question remains: how did the evolution manage to come up with such an elegant solution? And as I read recently (*), there are still so many things about life we don’t know yet…

(*) http://baldscientist.wordpress.com/2013/11/10/what-is-life-spoiler-alert-nobody-knows/