Blog Of Life: Molecules, so many molecules

There are SO. MANY. MOLECULES. Like, seriously, I couldn’t even begin counting them even if I wanted to. A big subset of them are biomolecules. And just like the other set, biomolecules can be divided into general groups, each with its own properties and function in a cell. We shall see how these molecules perform these functions, why and how they came into existence.
Cells are literally factories. They produce molecules in extremely high rates. For example, the body uses over 50kg of ATP every day. ATP is one of the most used molecules to get biochemical energy and I’m pretty sure everyone knows this one, but I’ll add a little more depth here to provide some context. The A stands for adenosine, which consists of adenine (a basic, aromatic (more or less meaning a ring where the bonds create a continuous electron stream inside the ring making it a very stable molecular structure) and a ribose (which is a sugar that consists of 5 carbon atoms: a pentose)). The TP stands for triphosphate, meaning there are three phosphate bonds linked to each other. You can convert chemical energy every time you split one phosphate off this ATP molecule, but the first (and furthest in the chain) that gets split off gives the most energy to use. I could dive into enzyme kinetics here, but l shall refrain myself from boring you to death. The ATP was an example of a molecule being used in a very natural way, but we can also exploit these cellular factories to produce large amounts of a certain molecule we want. Currently there are projects in the works for producing (human) antibodies and viral components for vaccine development in plants; we manipulate bacteria to produce large amounts of insulin and we use and manipulate the production of antibodies from camelids (camels and llama’s) for potential therapeutic uses, because they are smaller and are potentially able to pass through the blood vessels of the brain (the blood-brain-barrier) for example.
Anyway, this ATP molecule is interesting, because it has a mix of different compounds, which is also a commonality, to further diversify the ways of which molecules can obtain certain properties that can be involved in specific ways (structures, reactions).

If we extrapolate the concept of the combined compounds we could almost claim that, because of the close interaction of all these molecule, every cell is one giant macromolecule that’s continuously changing. If we take a more romantic approach, we could draw a parallel with the interacting molecules and the way we interact with other people and other organisms. If we go back in time and look at the formation of the first cell, and apply the concepts of cell division and evolution, every lifeform came off of that one cell, so every lifeform (uni- and multicellular) is related with each other and is linked in one way or another. However, I think that the existence of the cell could have emerged more than once. My argument comes from the fact that in evolution certain organisms have developed certain properties separately (for example multicellularity in plants and animals).
To make things even more needlessly romantic, to take humans, a multicellular organism, as an example, we have so many different cell types, all working together towards producing offspring. The gross majority has the DNA to actually become whatever cell type they want, but in order to create a complex body to let it work towards perpetuating its own species, they make sacrifices in a way so they get less access to their own DNA. They literally constrict their own potential for the succession of its most fundamental aspect, the genome (albeit that is debatable). This is one of the big concepts in developmental biology, which I’ll dive into on another time.

To continue in the theme of ATP, the constituents adenine and ribose (and phosphates) are building blocks and the basic forms of which biomolecules are made of. A lot of biomolecules are polymers, which means they’re big and long molecules made up of these structurally similar small building blocks, making them get unique properties. DNA or RNA, proteins, polysaccharides, fatty acids (not really a polymer, but I guess I’ll put it in here) are general examples of polymers. Combinations of these polymers with building blocks of other polymers are very common. The building blocks of these polymers can be divided into 4 big groups that make up almost the entire architecture of the cell. Every polymer and complex compounds has unique structural properties so the components of the cell can exercise their unique function. Membranes compartmentalize the cell, the outside or the inside; proteins perform structural integrity, specific reactions and interactions; DNA harbors the entire code into which an entire organism can be made (not completely true, but close enough).
These 4 groups that make the structures with specialized function are the following:

Sugars (or saccharides)
These are monstrous molecules, because they’re so diverse, yet so elegant in their structure. This group, together with the fatty acids, are the archetype of carbon chains. You string 4 carbon atoms together, add a hydrogen and a hydroxyl group on each side (-H and -OH) and add an extra H on each end of the chain and voila, you’ve created a sugar. Here’s what glucose typically looks like:
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It’s the cyclic form of it. It’s what happens in a solution of water molecules. The linear form, or open chain form turns on itself creating this structure, which is very rigid and can be chained into polymers that have different properties and function. The most right carbon atom, harboring the H and OH is called the reducing end of the molecule. This is because it can react with another molecule (this is mostly -maybe even always I’m not sure here- a sugar as well) causing it to lose an electron (from the –OH binding) and donating it to the other molecule, eventually forming a bond between them. The way this H and OH on the carbon are orientated, can also be reversed (the OH on top and the H on the bottom), making other bonds have different properties. The orientation of the H and OH group make it an α (OH in opposite orientation of the CH2OH at the top) or a β sugar (OH in same orientation of the CH2OH). The bindings between sugars have a conventional notation in the sense that they use the binding between the carbon atoms as information on how the binding is formed. The far right carbon is the first carbon, and then they count to the CH2OH as the last one (here 6th). So a 1->4 binding would be the first carbon atom (the reducing one) of the first sugar is going to bind with the 4th carbon atom of the second sugar. Prominent polymers consisting of pure sugar are (branched) amylose (chained α(1->4) glucoses) and cellulose (chained β(1-4) glucoses). There are many more, but they have extra stuff hanging on the sugars, making them not pure sugars (chitin in the exoskeletons of crustaceans and insects and peptidoglycan in the cell wall of bacteria).
There’s also in interesting non-reducing sugar, called sucrose (made from glucose and fructose), where both reducing ends react with each other, causing them to not interact with other molecules, making them very stable compounds. Plants make this disaccharide in leaves and transport it to roots, to be used or stored. Because the sugar is not reactive (with other sugars), it’s able to travel all the way to there without losing its potential chemical energy.
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Lastly on this group, I’m going to leave you with a little thing to think about. The amount of possible sugar conformations is astounding: you can go from 4 C atoms, all the way to 10 (probably even more) and the conformation of the molecule itself (how the OH and H are oriented on the C) make it so you could have way more information stored in a structural way to do the work for you instead of a molecule like DNA. So why is it that the nitrogenous bases (coupled with a ribose, a 5 C sugar, which is coupled with a phosphate) are used for keeping information stored with only 4 combinations, when sugars could provide almost infinitely more?

Amino acids
Ah, here we have my babies, the amino acids. We got 20 different amino acids with different physicochemical properties making them ideal for building blocks of proteins. The archetype of an amino acid is something like this:
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It has a NH3 group at one end, chained to a C-atom (the central C atom) which is bound to a H atom, a variable group (R) and a terminal COOH group. To make it easier we’ll say the backbone of an amino acid is a N-C-C block with the magic happening at the C in the middle. The chemical properties of the amino acid change with the environment: the NH3 can take up a proton, thus becoming positively charged, while the COOH can give away its H, making it negatively charged. These are the 2 outer charged states of the amino acid, but it can also be both negatively and positively charged at the same time (happens when certain pH values are met depending on the amino acid itself) and we get something we call the zwitterion.
The variable group is the real interesting part of the amino acid, though. It can hold straightforward chains like –CH3 or –CH2-CH3, or just an –H.
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It can hold potential positively charged amino acids like arginine
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and lysine.
It can hold potential negatively charged amino acids like aspartic acid or glutamic acid. Some have a sulfur group like cysteine, which is important in building sulfur bridges, a cohesive bond between 2 amino acids that can be far away from each other in the primary chain, but more on that later). You can even have extremely complex amino acids like tryptophan [image loading]

or proline. Each have their own contribution to the protein and make it so it a certain form can be attained and function can be exercised.
We have tools to make our own amino acids, but we cannot make all of them, so we need to get certain amino acids out of our diet. Those are called essential amino acids and involve biochemical steps to make that other organisms possess we do not (sucks to be dependent on the great Mother doesn’t it?) Other amino acids are weird, like selenocysteine [image loading]

,
which is an ordinary cysteine, but with Selenium instead of a sulfur group. This one, although rare, is found in proteins of humans too, so we can extend the amino acids to 21. There are a few other amino acids found in nature other than in humans that I won’t discuss, but I’ll link them here if you want to check them out (N-Formylmethionine (fMet) and Pyrrolysine (Pyl or O))
The last thing I’m going to give you guys is how amino acids are chained. First you get a peptide bond: a COOH of one amino acid (or peptide) reacts with the NH3 of another peptide, releasing an OH from the COOH and an H from the NH3 (=releasing it in the form of water), making an N-C-C-N-C-C chain. Then we can chain the next peptide until we reach the n-th peptide to eventually get the length to make a functioning protein. It’s important to note, however, that the formation of the protein happens after every peptide has been added in the chain. I will probably write a little more in depth about proteins and how they get to their form and function later, but that’s too broad of a subject to bring that up here.

Fatty acids [image loading]

(n = [2-34])
This one is kind of ambiguous, because it isn’t a building block in the conventional sense. Fatty acids are just a carbon chain with a COOH group at the end. That’s it. However, their relation to glycerol (which is basically a sugar made up of 3 carbons) and other groups (some structure with phosphate group or these guys (yikes!)), makes them have great variability in structure. The interesting thing about lipids is that they can make membranes: physical barriers that make compartmentalizing of a cell possible so it can exercise its specialized functions. Basically there are 3 different kinds of fatty acids: branched, saturated and unsaturated. The chained form predominantly present in Archaea (some type of prokaryote) and have an ether bond instead of an ester bond when linked to glycerol. The ester bond is what happens when a standard fatty acid links its COOH group to the OH of glycerol. The H of OH and an OH from COOH leaves in the form of water and an ester bond is formed. The C has bindings to the O of glycerol, a double bound O of the former COOH molecule and the variable C chain. Standard ether bonds also happen in mammals. The binding to glycerol makes the molecule (glycerol + 3 fatty acids) a triacylglycerol. Long term chemical storage is done in the form of triacylglycerol deposits in a specialized cell called adipocytes which can have a lot of their cell volume stored with these molecules. [image loading]

Then there are saturated and unsaturated fatty acids. They have a similarity between them: the length of the chain. The difference is the amount of hydrogen atoms are bound to each carbon atom, making it so that certain carbon atoms, if 2 succeeding C atoms only have 1 H atoms bound, have a double bond. Whenever a double bond is introduced in the C chain of a fatty acid, we talk about unsaturated fat. When there are no double bonds found in the carbon chain, and every C atom has the maximal amount of hydrogens bound to it, we speak of saturated fatty acids.
Of course, just like with certain amino acids, there are certain essential fatty acids that we ourselves cannot make. At the moment we know of 2 fatty acids we cannot make ourselves: the omega-3-fatty acids and the omega-6-fatty acids. These are unsaturated fatty acids with a double bond between the 3rd and 4th C atom and 6th and 7th C atom respectively (counting starts from the carbon that's not the COOH, the omega C). This is why the butter and other fat selling industries always market to these fatty acids. Every other fatty acid can be made from one of the starting blocks of the Citric Acid Cycle: acetyl coenzyme A.
But then we have this motherfucker: [image loading]

Looks menacing, doesn’t it? It’s a natural fatty acid in mustard oil and colza oil where high amounts of it in oil cause heart disease in mammals. To combat this a genetically modified plant (through conventional breeding methods) was produced which has a mutation in a certain biosynthetic enzyme so only 2% of erucic acid would be present in oils extracted from the plant. The oil extracted from the mutant plant is called canola. As you can see, genetically modified organisms don’t have to be scary business, they have been attained in natural ways for thousands of years. The ubiquitous wheat for example, can be hexaploid (twice has a 2n genomes of a different species been added and taken up into the genome of wheat) and in addition has been crossbred many times through the centuries.

Nitrogenous bases
These are the bad boys, coupled with a 5-C sugar (a pentose) and a phosphate to make the polymer called DNA. You have the nitrogenous bases called pyrimidines and nitrogenous bases called purines.
Pyrimidines: a ring of 6 atoms with various small sidechains (like =O or –CH3 or –NH2) where 4 atoms are C and 2 are N. The 2 pyrimidines of DNA are cytosine and thymine. Here we see a cytosine
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.
RNA has a different base instead of thymine: uracil, which is basically the same molecule, but without a methyl (-CH3) group.
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vs.

The purines are a bit more complex. They share the same 6 ring (again with the variable sidechains), and one side of that 6 ring is the bases for a 5 ring added to it. This is what adenine and guanine look like so you might get a better grasp on my poor wording:
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and

The purine bases are the same in DNA and RNA.
The physicochemical properties of these 4 bases makes it so they are complementary. This means that a certain purine can have an electrostatic interaction in the form of hydrogen bonds with a pyrimidine. The adenine interacts with the thymine (or uracil in RNA) in 2 places and the guanine interacts with cytosine in 3 places. One such an interaction with 2 bases is very weak, but chain a lot of these bases together, and have a complementary chain to create millions or billions of such interactions and you get a very stable molecule. Intuitively, when a higher amount of molecules with 3 interactions is represented in the molecule, instead of 2, the molecule will be more stable. The longer the molecule is, the more stable it also becomes. Stability is often measured through the melting temperature, where heat makes the double stranded (complementary strands; dsDNA) dissociate from each other. If 50% of the dsDNA molecules have dissociated and become single stranded, we mark that as the melting temperature.
I shall write a lot more about these fascinating molecules later on, where we will see function, interaction and structure. But for now, this is kind of it for now.

There are more molecules that make up the cell that interact separately or inherently with these polymers. For example cholesterol is in the cell membrane to give some more dynamic properties to it (makes it more fluid at low temperatures and less fluid at higher one’s). Another one is a building block of a waste product of fermentation of lipids or sugars in certain bacteria called 3-hydroxybutyrate. The bacteria chains them into polymers and deposits them as a carbon and energy reserve. [image loading]

This polymer can also be used as a biodegradable plastic and the mechanisms these bacteria use have been introduced in plants so they can mass-produce these bioplastics. Of course there are more types of molecules I haven’t mentioned, but that’s a list I don’t want to start with (because it’s never-ending). A topic about more specialized molecules will come later.

How are all these molecules formed? One big answer to that puzzle is enzymes. A lot of molecules need a lot of heat or pressure before they can be formed from other, smaller molecules. Heat and pressure are such important properties. They cause vibrations, rotations and flow of electrons in the molecules causing them to restructure, making them able to connect with other molecules and form a new molecule if the heat and/or pressure have reached a certain threshold. Enzymes can lower these thresholds so they don’t need as much energy to be formed. They are proteins and have a special structure in themselves called the catalytic pocket. The molecule specifically binds with the enzyme so that it can induce a change in how the electrons flow in the molecule and enzyme, making temporal structural changes in both bound molecule and enzyme. Ultimately the molecule is changed to the one that is “needed” and is released from the catalytic pocket. The enzyme can work in one way: A forms B; or it can transform A into B, but B can also be turned back into A. Enzymes can need other factors or could bind more molecules before it can function the way it needs to. This is a process we call allosteric modulation. But the scope of enzyme kinetics and their function is, just like many touched topics here, a little too broad to keep talking about them, so I’ll leave them for now. I will definitely revisit them, however, because enzymes (and proteins in particular) are really awesome.
Hmm, this became a little longer than I expected so I’m stopping my rave about structural molecules here, because this could actually go on forever.
See you for the next part, cheers.

PS: apologies for the bad sizes of the images, I just saved them etc., didn't really care about that in the beginning… I'll take that into account for next time.

Blog Of Life: Molecules, so many molecules

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