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Hi there. Good afternoon. Hi there. Good afternoon. I'm not sure whether it's afternoon, evening, wherever you are, but I'm really grateful for your company right now. My name is Veronique Berman. I'm a biochemist, molecular biologist. And what I'm going to be sharing with you today is an overview of various different very important fundamental macro molecules that are of huge importance all the way through every aspect of what you're going to be doing really fundamentals and the building blocks. Um So I'm going to be starting off by talking about carbohydrates, lipids and proteins looking specifically at their functions. Um and always trying as best as possible to relate structure to function. So this is something that we kind of really as biochemists needs to be thinking about is how every molecule relates to its function. So the cell chemistry is really based very much on the carbon molecule. Um Of course, there's gonna be other molecules that I'm gonna be talking about inorganic molecules. But when we're talking about organic molecules, we're talking about a backbone, a basis of carbon and that's associated with a huge number of stable molecules. And the major families that I'm talking about on the left hand side of your screen are the sugars, they are the simple molecules of the sugars um that build up to make the larger units which are the polysaccharides. And I'm going to be talking about that in more detail. I do have some references on the bottom of the slides. I'm hoping that these are sources that are available to you. But if not, I'm sure if you go back to the moderator, I can try and, and help to access more information on what I'm going to be talking about today. But we're talking about the building block molecules that carbon is the backbone of. So we're talking about the sugars, the fatty acids, the amino acids, the nucleotides, which of course, are all going to give rise to larger molecules. And we'll delve more deeply into that part of the reason why we're delving deeply into that is because of the role of these molecules in all cellular processes. So if you look over on the left, you're looking at a typical cell. Um 70% of which is water where I'm gonna mention water a little bit later on. But 30% of the chemicals that we're gonna find in the cells um come under the cat category of the macro molecules, the large molecules that have come about from the building blocks of the smaller molecules. Um And although the cell that you're seeing there is a bacterial cell interestingly if you take any other cell, um a eukaryotic cell, um animal cells, plant cells, you're going to see a similar distribution in terms of how the structures and the molecular bias ranges um looking at these macro molecules. So of course, they're predominantly water, but then all of the other macro molecules involved a large part protein, but then also um all the other molecules that you see on the right hand side of the panel, um just as a point of housekeeping. If anybody finds that um I'm speaking too quickly or too slowly, feel free to mention that in the chat and I will slow down or speed up accordingly. Um But otherwise, I'll just keep going. Um on this slide, I've actually um I know it looks terribly busy, but I've actually tried to bring in um where these small molecules. So if you look down the middle of the panel, you're seeing molecules that I've already mentioned um the nucleotides, the proteins. Um So that's on the macro molecules, the large molecules are on the right hand side in the center, it's the small molecules, the building block molecules, the amino acids. But on the left hand side, I'm also mentioning some very important inorganic molecules. So those are the non carbon based molecules like the phosphates, the nitrates, um oxygen, these are the very important molecules um and compounds that are going to be making up and, and really sort of um having an important part in the macro molecules as well. We know, and this is really just an example of things that can go wrong um when you have large molecules um that have a particular function. So for example, the hemoglobin is a protein that is regularly discussed, partly because of the centrality to the red blood cell and the ability to carry oxygen. So if you look on the lower right hand side of the panel, you can see a hemoglobin molecule and how the oxygen binds to it to make the oxygenated hemoglobin. That's the lovely bright red stuff or the deoxygenated when the oxygen has been delivered to the cells, uh for respiration, um the the ability for the hemoglobin molecule to carry that oxygen molecule and deliver it through the blood stream. What we know is that those structures, those um molecules, those proteins are actually quite involved and quite intricate. So, in your hemoglobin molecule, you've got two alpha and two beta proteins, I'll talk about the sheets and be the bleats and those are the different secondary and tertiary structures of proteins. Um where a simple single DNA change brings about a single amino acid change, which can then have a real, in some cases um catastrophic effect, but a very important and significant change to the function of the hemoglobin molecule. So this is really just an example of how one ends up with a really difficult disease, sickle cell anemia. Um A disease that you will come across um multiple times during your medical career, which is a single base change that results in a single amino acid change, which results in a total distortion of the functionality of a specific protein. So the reason why we spend time really having an understanding of these building block molecules within biochemistry is to best understand what's going wrong. You need to have to understand what goes right. Um And so really understanding how you have simple individual molecules monomers, one molecule joining together to make polymers. So that's combinations or chains of individual molecules joined together to make polymers. So on your, I just wanna see if my cursor actually works. I'm hoping you can see that on the right hand side here, you have the unlinked individual monomer. And then on the left hand side, you see how you can join them together to make um polymers. So that's many monomers joined together to make these structures that we're talking about. And in so doing, you're losing a water molecule. So that means that it's a condensation reaction. Um And you're then generating these large polymers, these large molecules that will be used um throughout the body for different functions. So again, and it a suggestion of how you join molecules together. So here you have individual carbohydrates, so individual monosaccharides. So here you have a glucose molecule here you have a fructose molecule and I'm drawing your attention to the structures looking at how many carbons. So here you've got um a five carbon ring here, you've got a six carbon ring looking at how many carbons are involved, looking at where your hydroxyl your oh groups are located. Um Sorry, those are really important um in understanding how the combination of the monomers. So that's your individual monomers up here joined together to form. Firstly, you get from monosaccharides, that's individual sugars to disaccharides, that's two individual molecules that's joined together. And I'll show you in a moment how you can join further together. So this is formation of what is called a glycoside bond. So down here, you have the glycoside bond and of course, the understanding of how those bonds form is really quite important. Just trying to scroll ahead to the next slide. I'm not sure why. OK. Sorry for that. Um So what you can see here is how the exact same process will be done in terms of transmitting genetic information. So another kind of macromolecule is making the DNA, the deoxy ribonucleic acid, then the RNA, the ribo acid and then the protein. So you have a chain of events where you have different monomers that are coming together to make different polymers, which will then carry information down the line. So what you see here is your DNA sequence, your individual bases, which then get um translated into your amino acid sequence, which will give rise to a structure. So showing you the importance of again, this process of building up individual monomers to make polymers to then make molecules that carry and transmit information. So, so far, what we've talked about is the cell chemistry is based on carbon. Um And that's your individual molecules that come together that are assembled as building blocks to make macro molecules to make large molecules. And those large molecules have a very important place in and then building and assembly and making your much larger molecules. And we used an example of where that can go wrong in your hemoglobin molecule, where you then end up getting um a sickle cell anemia because you have a hemoglobin that has an individual change. So looking more closely at the carbohydrates, I mentioned before that you have the monosaccharides that come together to form disaccharides and then polysaccharides. What is the function of these particular types of molecules? It's the fuel, it's serving to build first of all other materials that will be used in different parts of the cells and it's also providing the cells with fuel. So it's quite important to, first of all understand the structures, then how that structure relates to a specific function or maybe more than one function because molecules can do more than one thing. And an example of that would be your carbohydrate molecules which are providing building materials as well as fuels. Um I know I'm talking about glucose a lot, but that's because the glucose molecule is so central to not only building the various structures within the cells, but also the um fuels the the necessity for glucose in all aspects of respiration. Um And that the ability to make these glycoside bonds is quite important. And what you see here is the different structures of glucose. So you can represent these molecules as a biochemist, you can be representing your molecule as a formula or actually looking at the structure of it. And the structure of course, gives you a much better understanding of how that molecule is likely to be used. So you've got at the top of the panel here, the linear form for glucose. But actually, that doesn't give you too much of an understanding of how the monomer will then go forward to form polymers and and the glycoside bonds and how they will form and where the hydroxyl. So what you see here in blue is the hydroxyl group and the difference between the alpha arrangement and the beta arrangement of the glucose molecule is determined by where the different hydroxyline and hydrogen groups are located. So I mentioned the fact that these are building block molecules, the polysaccharide molecules will form both the um glycogen storage molecules. So that's giving the energy at the time that the glucose is being produced. Um So if it's in a plant, it's going to be used, it's going to be produced by the is a photosynthesis and it's going to be used immediately for respiration. But then we know that molecules of glucose that are not used will either be stored um as starch in the plant or glycogen in the animal cells. And they'll also be used um for growth and repair of the plant or the cell animal or plant cell. So now looking further at more of the structural processes that these molecules, these building block molecules are able to be engaged in. You can see from the top of the panel that you're gonna have um your alpha glucose subunits. So that's your monomers joining together to form polymers. And you can see here your individual um glycoside bonds that form between each one of the, one of us. And what we know is that they are capable of forming different storage molecules depending on how they are arranged and organized. So they're all still glucose molecules. But the question is whether or not they're are alpha glucose molecules. In which case, they'll make amylase and amil. If they're beta glucose molecules, they'll make cellulose, whether they're branched or not branched will depend on the type of storage molecules that they make. So whether they're starches or glycogen moving on now to the lipids. So putting the um carbohydrates, the glucose molecules, the macro molecules to the side, looking at lipid molecules. So lipid molecules are also made up of carbon, hydrogen and oxygen, but they look very different and that's because they're arranged very differently. Um The main um purpose of the lipids is the energy store. So they're stored as triglycerides. They have a hugely important function in um membranes. So, phospholipids and I'm gonna go into quite a lot of detail on the phospholipid bilayer later on, as well as the glycolipid, which are really important in terms of messaging and in terms of transmitting of information. So the lipids are a class of large biomolecules. They're not formed by linear polymerization. So what you saw up until now was linear where you're just adding one glycoside bond after another, after another. And when we look at um structures, you'll see again this idea of linear uh polymerization. This is not the case with the lipids, this stands on the side, but they are macro molecules and that's mostly due to their large size but also the critical role that they play. So the facts we're kind of used to looking at um butters and oils and, and, and the conversations about um saturated bonds and unsaturated bonds and how animal fats tend to form saturated bonds. So that's whereby each carbon is involved in a single carbon carbon bond to make this what would generally be solid at room temperature types of fats and then your unsaturated fats, which will have at least one double carbon, double bond or possibly more, which will therefore make for liquids at room temperature. And so, you know, we're used to the conversations about the benefits and the risks of these different types of fats. But just understanding how the molecules look is helpful in understanding how those are classified the triglycerides um are the important molecules that we we're looking at here that come about as a result of the fatty acid chain. So you see um in the middle of the panel here, you see the fatty acid chains. So those are the long chains and those chains can either be saturated as you saw or unsaturated. So at the bottom here, you're seeing there's one here with a carbon, carbon double bond, all the others are saturated. It can be, it can vary, they can be all the same or they can be um each one different. But you've got these long chains um connected to a carboxylic acid and they will join with a Glycerol molecule to form this triglyceride, um which is the glycerol molecule here. The fatty acids here. You have what's uh this the bond forming here and that's where you get your triglycerides. The relevance of this to the phospholipid is hugely hugely important. When we're looking at the um membranes, the phospholipid bilayer, you'll hear different terminologies for the same thing. But what you have um at the bottom of your panel here, I'm hoping that you can see my cursor is you have the fatty acid chains that I mentioned before. You have the Glycerol here. And then above that you have the phosphate group. Now, the importance of this cannot be um stressed enough that the differences between the hydrophobic and the hydrophilic behavior gives rise to um the mosaic model as it's referred to of the um membranes. And if you look more closely, I'm just really drawing you in to get a closer look and a better understanding of how this um phospholipid works. So again, you've got your hydrophobic tails here. So those are your fatty acid tails, you've got your Glycerol molecule that's really kind of the pin holding it all together. And then you've got the phosphate on the top, which gives it this hydrophilic behavior. And this whole hydrophilic head is what's going to be so important in the interaction of the membrane between the inside and the outside of the cell. So when you look at this figure, which uh it's kind of a bit gordy in color and quite busy. But hopefully, it's going to give you some inside, look on what this bilayer looks like. So your yellow sections here are your hydrophilic regions, the green bits in the middle that look like grass are your hydrophobic region. So what's happening is the hydrophobic region is being brought into the center to get away from any water molecules. And you've got your hydrophilic head and tail because you've got the outside on the top and the inside which is on the inside of your molecule. And then going through, passing through the middle of that, you've got your channel proteins and those are in red. And then you've got on the surface, your glycoprotein and they will all form different functions. And I'll, I'll go into that in a little bit more detail later on. But the, the important point is that using the hydrophobic and the hydrophilic nature of the phospholipid, you are able to form this intricate structure and this intricate structure allows you to bind your organelles. It allows you to have control of what enters and what exits the cell and how it does it. Um So, for example, using the tran membrane proteins um or the channel proteins um as well as um communicating the cell being able to communicate with the outside, using the glycoprotein and the side chains, the carbohydrate side chains on the carbo on the glycoprotein moving on now to proteins, proteins are of course, the building of most of the structures that we are gonna be looking in in all areas um of the cell. But we need to look at how that protein comes about how that structure is formed. And probably there isn't anywhere in biochemistry where the structure relating to the function is more important. But we need to go back and look at the outset how we build those protein molecules in the very first instance. So we're starting off with amino acids that come together. And this is again an example of linear polymers. So we're going back to similar to um the formation of the glycoside bonds. Here, we're gonna be looking at forming peptide bonds um to make a linear protein, an amino acid which will give you a primary structure. Now, here there is a hierarchy or a stepwise progression of how the structures are formed. And what we know is that depending on how that pans out and how that process looks will depend on what you actually end up with um as a protein molecule at the end. OK. So the proteins I've just given you here really a very quick list of the diversity of the biological functions of the proteins. And I can't stress enough that, you know, there's new proteins being discovered all the time, there's new um uses of different proteins. We use um proteins therapeutically, we use them to deliver drugs, we use them to do so many different things. But having an understanding of the function and where we can use the proteins is really quite important. But I think this is pretty basic and you've probably met this all before. The spider diagram is really just to give you an idea of how far reaching um the roles of proteins are, whether they're structural molecules, whether they're hormones in the endocrine system, whether they're using the immune system, um The numbers of different enzymes that are involved in catalyzing reactions is all based on proteins. So really just to give you again an overview of how important these molecules are. Um I really just threw this in to add a bit of color and fun. But just to give you an idea of the amazing modeling that is being done, the amazing understanding of how the different secondary and tertiary structures come together to be able to create the functional molecule. So just down here, you can see how the antibodies, how if you look here in the middle of the structure, you can see how antigens can bine to antibodies. If you look up at the top of the structure, you can see how oxygen can bind to the hemoglobin molecule I mentioned before the two alpha chains and the two beta chains, how those come together to form a tertiary and then a quant structure so that the the molecule can do what it needs to do. So the structure is so very, very important and having a deeper understanding of that is so helpful. I'm just giving you here another example of keratin whereby we can look at the um the molecule of keratin and see how that there's fibers come together from the alpha helix proteins by bringing together lots of those alpha helix and winding them together to then make the myofibril the microfibril to then making the individual keratin molecules. And that's where you see where it ends up. So where does keratin occur? Well, there's a good example of where, where you'd find keratin, but there are of course, so many, many, many other uses of those molecules. But it's just having an understanding of how those structures come about also to talk about the non covalent interaction. So there are lots of weak interactions that are taking place between different parts of sorry, that um molecules and how they bind together to stabilize the structures and how the end result the end structure is so important for the function. So let's just take as an example, hm sorry enzymes. An enzyme is a highly specific molecule that will only have one substrate or substrate that will bind to it, that is totally dependent on the shape of the molecule. If the shape of the molecule isn't appropriate, then it will not bind to the substrate. The enzyme substrate complex will not form and the enzyme reaction will not happen. That enzyme structure comes about directly due to the amino acid sequence that has folded that has given rise to that um active site where the substrate will bind. Likewise the um understanding of the nucleic acid sequences DNA sequences that become the RN A sequences that will be recognized by the transfer RN A molecules to bring about the polymerase polym of those amino acids. Again, is critically important to understanding how the structural molecule will then form. So I'm just going to mention here um a few important interactions, um hydrogen bonds, um sorry ionic interactions is one, the hydrogen bonds which form in the formation of quite a number of structures. So, for example, the double stranded DNA that forms as a result of hydrogen bonding, the van of val forces is another force and of course hydrophobic interactions. So I mentioned before um in the lipid, you've got the phospholipid where you've got the hydrophobic tails and the hydrophilic heads. Of course, the most useful example of understanding hydrophobic and hydrophilic interaction is the water molecule whereby you have areas of the molecule that are polar where you have um areas of attraction and repulsion of different molecules. So this concept, this theory is very important, it carries through from as basic as the water molecule into the whole understanding of the tertiary and um quinary structures of the globular proteins just to dwell on that a little bit further looking at um polarity which is means areas of charges, there are um nonpolar groups. So for example, your hydrocarbons, they tend not to be polar. In other words, they don't have areas of charge. But then you have quite a number of um issues of polarity when you have um oxygen molecules, when you have um carboxylic acids, um hydroxide molecules, amino molecules. So there's quite a number of different scenarios where the polarity, the areas of charges will have an impact on how the molecules will then bond, how the molecules will form different structures and how they will interact with other molecules. So understanding for example, how hydrogen bonds form which groups are able to form hydrogen bonds is helpful because we know that there are certain um bonds that are hydrogen donors. So they, if you look for a group that contains a hydrogen atom, which is bound to a nitrogen or an oxygen, or you look for the hydrogen acceptor. So that's looking for where is the electron, where are they likely to be attracted to the hydrogen and to make the bond with the hydrogen. That is quite an important point when looking at the interaction between different molecules and understanding how the molecules interact with each other. Also looking at the um hydrophobic effect, which I have already mentioned, looking at how nonpolar molecules aggregate are drawn to one another come together to release some of the um water molecules, looking at um nonpolar molecules being separate and then being drawn together um gives you some interaction, especially later on down the line. If you're looking at um antibody interaction and drug interaction within cells, understanding the differences between polar and nonpolar parts of molecules is very helpful. Um Still concentrating on water. I've mentioned proteins, polysaccharides, nucleic acids. They are all what we need to be thinking about these molecules is always thinking about them in the 3D. It's very easy when we're studying these molecules and we're learning about them, we draw them here one dimensional structures. It's often quite difficult to think about them as three dimensional structures. That's where using models and modeling is often very, very helpful because what we need to understand in the three dimensional structure is how these molecules will interact. And of course, the interaction with water bearing in mind that there's so much of it about and the forming of the non covalent interactions is extremely important to look at how these molecules work. So just for the avoidance of doubt, you can see from this slide here, I mentioned that water is a polar molecule where you have areas of positive charge, where the hydrogen ions are, you have areas of negative charge from the oxygen. And how the hydrogen is drawn to the oxygen from the neighboring water molecule or how the oxygen is drawn to the hydrogen from the neighboring molecule that gives water the cohesive. Um if you like sticky like behavior um as a result of being drawn to the charges of the next water or the neighboring water molecule. Um So this is sort of a fundamental um thing that we base so much understanding on, but it's useful to actually see graphically what that looks like. Um And we see that um extensively because the water molecules given their high reactivity and their high um cohesive tension, the ability to form the extensive ability to form the hydrogen bonds. Water therefore is as you've seen an incredibly important part of what goes on in cells and part of that is the ability for water to act as a solvent, the ability for it to hold. Um non pod groups of the are insoluble in water. But that means that large proportions of the nonpolar groups are less soluble molecule is in water. And that hydrophobic effect is important in globular proteins. And so that a tendency of nonpolar or hydrophobic side chains to sq themselves into the interior. And so in understanding which parts of the molecules are polar, which parts of the molecule are nonpolar will give you a good understanding then of how the structures will actually form and what they'll look like and where your side chains are likely to end up and where they're going to be um finding their comfortable space in making the molecules. So to give you an an uh a maybe a slightly better understanding graphically of what this looks like. So on the left, you have an unfolded polypeptide check and you can see that there are in blue, the polar side chains and in green, the nonpolar side chains. So by virtue of the fact that the green are nonpolar and therefore hydrophobic, when the molecule folds up, they're going to bring themselves to the inside, to the core to get away from the external polar molecules. And so they form the nonpolar core, the hydrophobic core. Whereas the polar molecules, the blue ones, because of the fact that they are able to form interactions with other charge molecules, they end up on the outside. So what you see is this um folded version of this unfolded molecule. But what you can see clearly is how the um nonpolar ends up on the inside and the polar ends up on the outside, um not dissimilar to what you saw with the phospholipid bilayer, whereby the hydrophobic tails end up on the inside and the hydrophilic heads end up exposed to the outside. And then you can see that the constraints of the water molecule on the um unfolded polypeptide chain, which is not going to have the same impact on the folded version, right? What you now see is how the folded version is then able to interact with other cellular molecules. And you can see here lots of water molecules surrounding and that makes the um aqueous cellular environment, um much more hospitable and how the folded polypeptide chain is then able to interact within an aqueous environment leaving the hydrophilic surface on the outside the hydrophobic um molecules on the inside. So to summarize so far, we've looked at general features of cells and some of the large molecules. OK. We've surveyed the carbohydrates, the lipids and the proteins touching on some of their functions, the general points of their structure. And examples of how they work as building blocks, how they come together to be important building blocks. And we've also looked at the cells environment of how those globular proteins are um folded, how they're driven, how they will work with using the hydrophilic and hydrophobic characteristics to form either the phospholipid bilayer or the globular effect of those different proteins. So all the while looking at the building blocks, how they come together to make structures and how those structures are then used functionally to perform a particular function, a particular purpose. So looking more deeply into the proteins, because of course, they are such central molecules. What do we need to know about the building blocks of these proteins, about the amino acids? So the amino acids um we need to be able to know which ones are polar and nonpolar. That's quite important because if we're going to be making structural molecules, we need to know how those structural molecules when they fold and go from a primary structure of a chain of amino acids to a secondary structure, whereby they're folding the polypeptide chain into either an alpha sheet or B deplete and then interacting the different secondary structures to make tertiary structures. We need to know what is polar and what is not polar, what is hydrophobic, what is basic or acidic? So we know the amino acids have an acidic proportion from the carboxylic acid. But in terms of the our groups, the um side chains, what's basic, what's aromatic in terms of the structures. And then understanding what the structural side chains um will what their structures will be and understanding how that will then pan out when you fold this molecule together. And of course, the ability for hydrogen bonds to form is an extremely important part of holding all these structures together. But they're not the only bonds that are necessary. We also rely on disulfide bonds, sulfur sulfur disulfide bonds as well as hydrogen bonds. So in order to gain that better understanding, I'm actually gonna take you back to the structure of the individual amino acid. So you have your amine group, your NH three group, your amine group here, which is why it's called um amino acid and your carboxylic acid, which is why it's called an acid and then your R group. And of course, the R group is what differs from one amino acid to the other. So there are 20 possibilities and it's the R group that's different. In each case, when you join together two amino acids, we make the peptide bond. The R group of the two different amino acids is going to be extremely important in understanding how the molecule will fold or how the um the structure will take shape what it's gonna look like because of the interaction between those side chains, those are groups. Um And just to, to say that when you take two amino acids together that forms a dipeptide and then the more you have um then you have a tripeptide that's three amino acids. And then multiple, we give you a polypeptide. And of course, the end result is something that looks like this uh which has got multiple um secondary structures. And then you've got this lovely molecule um which is your uh drug, for example, you using drug targeted therapy. Um as an example, the structure function relationship um to make those building blocks that will then go into the cellular environment is of course, so important to understand. Um I'm just putting this up as um for reference. Um You might find this is a a helpful addition in having a greater understanding, especially if you're particularly interested in protein chemistry. So, looking more closely at the amino acid sequences, um of course, I'm not going to look at the individual ones, but you can see that they're grouped together. So you have your aromatics, that's where you've got your carbon rings. That's why they're called aromatics. You have your sulfa containing um are groups so that they will give rise to your um sulfa sulfa bonds or your disulfide bonds. You have your polar and your um nonpolar, which are very important, as I've mentioned before, looking at the charges. So understanding what the R groups are, the functional groups on the individual amino acids will help to understand how the side chains will then either um repel attract form um bonds and the groupings um that you've got there, they're not absolute, but they're certainly helpful working guides to understanding how the individual amino acids will interact. Um Here, you can see just represented slightly differently, the nonpolar amino acids, the cyclic ones. So you can see here, for example, how the secondary groups here. OK. So that's your um primary amino acid. Then you've got the secondary groups, how they can come together to make um different structures. So here, for example, you've got collagen, which is a very important um protein which comes together and the branching of these chains gives you an important idea of how the function is. Again, focusing on some of the other amino acids. You can see um these are here, you've got nonpolar here, you've got more polar. So again, how they're going to interact? The need to understand these structures. I think I've I've stressed efficiently is for us to then gain a real insight into how the primary sequences of these amino acids. So here you see a chain, a beta chain which is in purple and you see an alpha chain which is in blue, how these two chains will come together to make a secondary structure. So the interaction between this sulfa on this group of the alpha chain with this sulfa on this cysteine on the beta chain, how you're now bringing together two chains, you're joining together two chains to make a secondary structure. And the secondary structure that you have to be seeing here is um the human insulin protein, a protein that you'll encounter many, many times. I'm sure of course, the knowledge again, of the charged and uncharged um is quite important and I just draw your attention to a couple of areas of um um Aspar gene glutamine don't confuse the names and their abbreviations. It's very similar to the days. Going back to the periodic table. Don't make the assumption that um because potassium begins with A P that the short hand is P it isn't. Um And the same way with the amino acids don't assume that the name of the amino acid will automatically give rise to the short hand. Um It's quite important that, you know the names of the amino acids. Um and know that the short hand isn't um doesn't automatically follow it. Um So for those of you that um are going to be looking at uh drug chemistry further down the line um understanding the stereo chemistry. In other words, the symmetry of the amino acids is extremely, extremely helpful and important. Um The carbon is attached, it has four groups attached to it, the AEN group, the carboxylic acid group, the R group, which is the functional group and a hydro hydrogen molecule. And of course, the we call it stereo chemistry. In other words, where those groups are oriented will make an enormous difference in how the primary structure will interact with other um amino acids to form the secondary structures. So, isomers are designed with reference and you can see here, um you've got the plane of symmetry is what is the determinant of how you annotate how you name and what is the relevance of where the functional groups are located. So, the plane of symmetry is as if you put a mirror down the middle um of the molecule to try and understand which orientation. So if you look at the plane asymmetry, you can see here that there's a difference in where it's not what's attached to the car, but that's not different. It's the same um groups, the carboxylic acid, the amine, the functional group and the hydrogen. But the orientation, in other words of where they are is relevant and that is um stereos specific or stereo chemistry. And you can see that in this example here, um which orientation you're looking at is giving you a good understanding of the um orientation of the molecules. The other point that is very important is we know that amino acids, you know, we talk about acids as though they are acidic. But actually when you have two amino acids that are weakly um ionizing, you have ionizing groups attached to them that will impact on the Ph that you end up with when you're joining your different amino acids. So the PH is, what is the acidity or the alkalinity that uh concentration of hydrogen ions or hydroxide ions? But the rule is that a PH below the PK A. So the PK A is the PH at which a weakly acidic group is 50% associated. So that's where your hydrogen is. So you've got that with the carboxylic acids and you've got it with the amine. So, the, that's what your PK is where the 50% of the um you have 50% dissociation. The rule is that at a PH, below the PK A um un dissociated forms dominate. So for example, the carboxylic acid, the Coh dominates below a PH of 2.3. OK. And above the PK A value. Um and that's uh the dissociation forms form dominant is the zero. So that's exactly the same with the um amino acid group. So the charge born by the amino acids depends on the prevailing Ph. OK. So, quite helpful again, when looking at the interaction between carboxylic acids, um and your various different R groups and your amino acids. Um and it's quite a simple way to calculate that. Should you need to um to compare the PH to the PK A? Sorry, I get to sign. OK. So I just want to look at um electrophoresis of proteins because I've mentioned the charges. And so the charge is a really important way in which we use not only to separate proteins but to separate other molecules as well like DNA. But the fact that they all have um the charge helps us to separate the proteins, but it also allows us to use then the masses of the individual proteins um to carry out what's called electrophoresis, which is allowing us to move these molecules through an electric field. So the the molecules will be loaded up into a gel. So here. What you're seeing in this figure here is a vertical gel where the samples are put into the well, um this is standing in a tank which is a buffer. So it's got ions that are free flowing in the buffer electrodes that allow you to connect it up to a power supply and you're loading up your sample into the well. And the charge will run through the gel and allow you to separate the gel according to the charge and the mass. And of course, the very small fragments will run through the gel very quickly because there's not much impedance because they're very small and the very large molecules will move through the gel very slowly because of their increased mass. And so that allows you to fractionate or to separate um the molecules according to their size and use the charge as a way of moving them. Whatever you do, don't go memorizing this. There's always tables to help you with looking at the PK A of the individual amino acids. But um it's just to be aware of the variation um in PK A values between amino acids. OK. I have alluded to this already numerous times, but I find this slide quite helpful in summarizing um the protein structures that I have mentioned. So we start off with our primary structure, which is our individual amino acids bound to the next amino acid to make the peptide bond the peptide chain. And that's the primary structure, the individual amino acids to make a nice long chain, that chain in itself is pretty useless because it's never gonna fit into the cell. It's never going to make a structure. Then you need your secondary structure and your secondary structure is bringing together one or more chains to make what are called either alpha helices or B depletes. Those are the shapes that the secondary structures will form. The secondary structures can then fold to make your tertiary structures. OK. And that's where you're looking at your functional proteins, your enzymes, for example, with their active sites, your antibodies, for example, with the um antigen binding sites. Um And in certain cases, they may go on to make your urary structures. So, for example, what you're seeing in this structure here is your hemoglobin molecule, which is your two alpha and two beta sheets. But you've got your I and your fe um coming in there to form that structure as well. The urary structure, which gives it its functionality of allowing the oxygen molecules to bind. So this is again, just um showing you what I've already showed you the primary structure. That's the linear sequence, the secondary structure um is maintained by the hydrogen bonds and that's important between the peptides. Um And then you've also got the tertiary structure um which is the arrangement of all the amino acids, all the R groups. And that's where draw your attention again to what I was saying before about the polar and nonpolar um the um organic sorry, the um rings on the tertiary groups on the, sorry, on the R groups showing how they interact with one another to make that tertiary structure. And finally, the quant structure where you've got more than one polypeptide in a multi subunit. OK. So that's really just summarizing what you've already seen with your um amino acids forming the peptide bonds. Um And just again, showing you how the charges and the terminals um make a make a difference. And, and where the charge when the peptide forms together here, you're seeing different charges on the R groups and how they can interact with one another. Again, just showing you how the side chains determine the properties of the peptide. Um really important in looking and understanding um the functionality of the amino acid chains and how they form their secondary and tertiary structures. And the function. What you're looking at here is understanding now how the protein we've seen how we make it. But it's actually quite easy to make that structure come apart. It's, it looks like a very sturdy structure, but actually, it's quite flimsy because what we determine what will determine whether or not that structure will stay stable and stay as it was is if you change the temperature or you change the Ph because by changing either of those two parameters, you can actually have quite a significant effect on what the protein structure looks like. So on the left, you've got a normal protein structure by heating that structure up by increasing the temperature, you cause a vibration of the bonds. So you've, you're gonna basically bring about the destruction of the molecule by adding kinetic energy to it and by causing the um bonds to break or even just to become unstable. And that, that causes the structure literally to unravel before your eyes. So it's quite important. Of course, we build the structures up but to know not only how to build them up, but then how to maintain those structures as well. Changing the Ph likewise will have a potentially very deleterious effect on these structures because of the hydrogen ion interaction. And that can cause the carefully balanced structure to come apart. Um So here, you can see a more in depth um example of how the structures, the primary and the secondary structures um come about because it's quite a nice little graphic to be able to compare and contrast. For example, what an alpha helix looks like, what a be to sheet looks like and how you can bring them together to combine a tertiary structure. Um That's showing you what a helix looks like um whereby you can see hydrogen bond interactions here. And you can also see how the side chains interact um to form your selective bonds, all side chains will project inwards uh from a helix. Um So there's no side chains inside the helix. Um the backbone is what makes up the helix. Um And so that's quite important. Again, if you're looking at drug interactions or, or other chemical interactions within um within um your structure, again, what you can see here is how you stabilizing your hydrogen bonds are stabilizing the structure. Um And how you can go from very simple structures to quite complicated and joining together multiple beta strands side by side by using the interaction of the hydrogen bonds to hold them together. Um And this is just really summarizing what you've already seen um in the structure. So the globular proteins are made up mostly of many secondary structures that contain both the helices, the alpha helices and the B depletes. And it's bringing them together the tertiary structures result in the folding of the chains and the closely packed 3d structure. And here you're adding your sulfa sulfa bridges um in many of the uh proteins, which is again important in bringing together the different parts of the molecules. And that's just to give you a, a, an idea of again of the tertiary structure and what that looks like and how one can then use it using alpha globin beta globin to show you what a myoglobin molecule looks like. Um And how you're literally building layers on layer of structures. Um Some further examples which you can see um I think I believe you'll have access to these slides beyond today. Um So that you can look at some more examples really there just to give you some more examples of different um structures and how those structures are important. Um I think I'm actually going to stop at this point um and not go into structures on antibodies. Um And I'll continue with the antibody structures in my next um session. I'm very happy if anybody wishes to send any um emails and if you have any questions, um is there anything further from before we sign out today? Um I don't, there's no questions in the chat box. So I think thank you very much for an amazing lecture doctor. Really appreciated it and I would really appreciate if everyone could fill out the feedback form in the chat. And um I hope you have a lovely evening doctor. Thank you so much M LA. You take care now. You too. Thank you very much. Goodbye. Bye for now. You too. Bye bye.