tinywow_video_to_text_65329983.txt

So, now we're going to talk about the biological macromolecules proper, and we're going to start with proteins, and when we introduce each of these different classes of biological macromolecules, we're going to start by introducing the monomers that make up these polymers. For proteins, that's going...

So, now we're going to talk about the biological macromolecules proper, and we're going to start with proteins, and when we introduce each of these different classes of biological macromolecules, we're going to start by introducing the monomers that make up these polymers. For proteins, that's going to be amino acids. So we call them amino acids in the amino side, because each group is going to have an amine functional group. And then acids, because each amino acid is also going to have a carboxylic acid functional group as well. These are the monomers, and it turns out both the amines and the carboxylic acids aren't going to actually exist largely when we form the polymer, so they're going to be tied up in amide linkages. But in free single monomer amino acids here, you've got both an amine group and a carboxylic acid. Now, one thing to note, so I've got them drawn out here, but that's actually not what they're normally going to look like at physiological pH around pH 7. So it turns out that the amine groups being a base typically are going to exist largely in the protonated state and have a positive charge at pH 7. So in the carboxylic acids are going to be an acid, going to largely be deprotonated, they're going to protonate water essentially, so they're going to exist deprotonated and have a negative charge. And so you've got a positive charge on one end of the free amino acid, a negative charge on the other end, and we call this a zwitcher ion. So we're defiling away in your head. So at physiological pH, most amino acids are going to be in their zwitter ionic form is what we say. All right, so other thing we want to take note of is this alpha carbon right here. So if you might recall from organic chemistry that the alpha carbon is defined as the carbon next to a carbonyl next to a carbon oxygen double bond. And so the carbon next door is called that alpha carbon. So this is what forms the backbone of any amino acid. You're going to have the amine nitrogen, the alpha carbon, and then a carbonyl. Amine nitrogen, alpha carbon carbonyl, and we start hooking these back bones together to make a polymer, you're always going to be following those three atoms in the backbone. Amine, alpha carbon carbonyl, nitrogen, alpha carbon carbonyl, all the way down the chain. Now attached to that alpha carbon, one, you're going to have a hydrogen. So but two, you're going to then have some variable group. So and that variable group is going to make the 20 naturally occurring amino acids different from each other. Now one thing to note, I say 20 different ones. I know there's a couple of oddball organisms that use a funky amino acid and stuff like that. We're just going to ignore that. But outside of those couple of funky exceptions, there are 20 naturally occurring amino acids that all living organisms use to make up their proteins. That's what's different here. And it largely comes down to that side chain right there. So if you take a look at that alpha carbon there, that alpha carbon is bonded to four different things for 19 out of the 20 amino acids. The only one where it's not is glycine where that variable R group is a hydrogen. In that case, the alpha carbon would be bonded to two hydrons. And glycine is the only amino acid that is not chiral. The other 19, they are all chiral. And one thing to note. Instead of using R and S, so like we might in an organic chemistry class more commonly, we use D and L for a lot of macromolecules like protein amino acids, as well as in monosaccharides as we'll see in a little bit. And one thing you should know is that for an amino acid, we always use the L amino acid for living systems. They don't use the D amino acids. We'll find out with sugars though. The monomers are D sugars in corporate and living systems. But with these chiral lovely amino acids, it turns out all of our enzymes that are going to use these to make proteins and things of a sort or recognize them. They all recognize only L amino acids, not D amino acids, also worth filing away in your head. All right, so depending on the variable R group here, you're going to have some different options. Again, there's 20 options. Glycine is just a hydrogen. Allenine would just be like a methyl group down here, a CH3, and they get more complicated as you go from there. And we can group them into a number of different classes. We can talk about the non-polar amino acids. And it really all comes down to that side chain right there. So because what we're going to find out is that you might look at this amino acid, like Chad, that's a really polar molecule, especially if you consider it's a whiterionic form. I mean, this is like textbook polar, positive at one end, negative at the other. That's what polar means. So however, we're going to see in a second that again, most of these amine and carboxylic acid groups are going to be tied up into amine linkages in the interior. The only one is that one end we're going to have a free amino group and then the other end we're going to have a free carbox group. But all the rest are tied up as amides and amides aren't acidic or basic. And they're not charged. And so, you know, we can't really say that these proteins, the amino acids in the protein are quite as polar as a free amino acid. And so as a result though, we classify whether or not we consider the amino acids polar or non-polar or things of this sort all based on that variable R group. If that variable R group is non-polar, that's a non-polar amino acid. Regardless of the fact that it's, you know, as a free amino acid, a very polar molecule. That's irrelevant when we're classifying these amino acids. So we're going to have non-polar, we're going to have polar, and usually when we say polar we mean but not charged. We're going to have acidic and we'll learn that a physiological pH that tends to be negatively charged. We're going to have basic and a physiological pH that tends to be positively charged. And as a subset, and I didn't really outline this on your outlines, but you could talk about aromatic amino acids as well, and they fall on a couple of different classes as we'll see. All right. So if we take a few amino acids and start hooking them together, what you're going to find out is you're going to actually have nucleophilic attack by the amine of one attacking the carboxyl group of the other. And that doesn't actually happen this way. This is all catalyzed by ribosomes and stuff, and I realize these aren't even in their zwitterionic forms and stuff. So I'm just going to kind of want you to see where the bonds are being formed. So but not showing a complete mechanism here by any stretch, you know, I could show nucleophilic acyl substitution going on stuff. So not what I want to really accomplish here. So what I do want you to see is that we're going to have a leading group here, and then this nitrogen is now going to be attached to this carbon right as we see down here. And the bond form between them, that is an amide linkage, and we call that in this specific instance between amino acids a peptide bond. So all peptide bonds are amide linkages, but not all amides are peptide bonds. You could have amides that are completely independent of amino acids, and those are not going to be called peptide bonds in that case. All right, so all peptide bonds are amides, not all amides are peptide bonds. All right, when you're forming that peptide bond, notice not only did you lose the OH here, but you're also lost one of these two H's as well. And that's where you get these water molecules that are formed in the process as well. And because we're forming water molecules, we call this a condensation reaction. And so when you're forming these peptide bonds, condensation produces water. So but you can also go the reverse reaction and break them, we call that hydrolysis because it uses up or consumes a water molecule. Now specifically, hydrolysis is kind of a generic term. So it can refer to breaking any carboxylic acid derivative using water. So but specifically with proteins, we can also call it proteolysis. So and there are proteolytic enzymes in your body that will cut amino acid in various places, including in your digestive tract. If you look like chymotrypsin and trypsin and things of a sort, they cut proteins following specific amino acids in the process of digestion and stuff like that, they're proteolytic enzymes. Now, one thing to note, we look at the backbone now and again, emphasize this on the last slide as well. But following the backbone, you got nitrogen, alpha carbon, carbonyl, nitrogen, alpha carbon carbonyl. And that's what the backbone is going to look like. Now coming off that backbone though, you're going to have on the alpha carbon, the hydrogen and then some variable group, that's going to be one of those 20 different things that are possible for the 20 different amino acids. And here I've just generically listed them as R1, R2, R3, they could be three identical amino acids. They could be three different ones. It is, you know, depends on just what protein you happen to be talking about. So I'm going to take a look at the different, the 20 different amino acids and you're going to have to kind of organize them in your head by class. You probably don't have to memorize the structures for the DIT or the OIT, but you probably should know which ones are polar, non-polar, acidic, basic things of that sort. So here's the non-polar amino acid. You've got glycine, whose variable group is just a hydrogen, alanine, just a methyl group, valine and isopropyl group. So of particular importance though, this is one that's unique here is proline. Proline connects the alpha carbon and the amine nitrogen, so with a five-membered ring. And so it's the only amino acid that actually the variable R group is connected to the backbone in a ring like that. So it turns out when you incorporate proline in a protein, because of this ring structure, it actually puts a characteristic kink into the structure of a protein. So and that means that they're usually going to get incorporated in certain places, but not in other places. All right, we got lucine, isoleucine, methionine, phenylalanine, tryptophan. So probably worth knowing the three-letter codes as well. And I'll put the one-letter codes as well. So and maybe you saw those in a biochemistry class one along the way, probably not something you need to know for the DAT or the OAT as well. So but the three-letter codes, knowing that GLY is glycine, totally worth your time. And again, knowing that these are all listed as non-polar amino acids, and again, even if you, my structure as well, you should look at these and be able to see like, oh yeah, non-polar, all carbonate hydrons, non-polar, non-polar, all carbons and hydrons, and the only one that's not all carbons and hydrons, and the only two I should say, are a couple here, methionine, which has a sulfur in there, but notice no hydrogen bonding or anything like that. And then also tryptophan, and tryptophan is a little bit tricky because there is some hydrogen bonding there with that NH bond, however, the bulk of this entire side chain is mostly carbons and hydrons, and it's fairly non-polar and gets classified as non-polar. Also note that both phenylalanine and tryptophan are also considered aromatic amino acids. So if you take a look at like chymotrypsin, chymotrypsin happens to cut after aromatic amino acids, including after phenylalanine and tryptophan. And again, you don't have to know that I'm just giving an example of why you might, you know, class something as aromatic. So now we've got our polar uncharging amino acids, we've got six of them here, we've got serine, threonine, cysteine, asparagine, tyrosine, and glutamine. So if you look at serine and threonine, these are both alcohols on the side chain in one way, shape, or form. And if you look at phosphorylating and stuff like this, phosphorylation often happens on a serine or threonine right on the alcohol group itself and stuff like this. So, but definitely polar and you recognize them as such because that OH there is capable of hydrogen bonding. So it's a small group with an OH, definitely highly polar, but again, not charged though either. So cysteine here, we've got an SH group, we're going to find out that cysteine does something special in forming disulfide bridges as a consequence of having this sulfhydral group. So, and whereas the SH is technically not considered hydrogen bonding, at least not in gen-camera-o-chem, there are some biochemists and biochemistry textbooks that actually consider the SH bond to participate in some smaller degree of hydrogen bonding. Now for the purpose of the DAT or the OA2, I probably wouldn't consider it hydrogen bonding. However, I just want to point out though that this is a still a fairly polar group. This SH group and that's why cysteine is being classed as one of these polar amino acids. If you look at asparagine and glutamine, they're both amides. So with a fair amount of hydrogen bonding, that's possible. And then tyrosine here. So with an OH, there is still some non-polarness too with this whole big benzene ring and stuff like that. But overall, it's still going to be classified more as a polar uncharged amino acid. Note that also tyrosine is also an aromatic amino acid along with tryptophan and phenylalanine we saw as part of the non-polars. All right, finally, we're going to talk about the cytic and basic ones and these are pretty important. So the three that are classified as basic, lysine, arginine, histidine. And they're basic and you might think something's going to be a little strange about them as being basic. Well, they're basic because in water, they've already acted as a base, which means they're largely in their conjugate acid forms. At least that's going to be true for lysine and arginine. And the conjugate acid, they're both amines down here in one way, shape or form. And the conjugate acid is going to actually be positively charged and that's going to be the predominant form at pH seven, at physiological pH. Now I listed the pKa's for both of them here and I don't expect you to memorize pKa's or anything like this, but I only did that to show that at pH seven we're more acidic than the pKa and when the pH is more acidic than the pKa, it will largely exist in the conjugate acid form in solution. And that's why these are largely in the conjugate acid forms and positively charged. And the fact that they're positively charged has unique consequences. One, we'll find out it can play a role in protein folding. So but also commonly say we'll find out that DNA is negatively charged and we'll find out proteins that associate with DNA like histone proteins and eukaryotes often incorporate a lot of lysine and arginine residues to give them a positive charge so that they can interact well and bind to DNA. So histidine over here is often again considered also a basic amino acid though with a pKa of six, well at pH seven we're actually more basic than that number and it's largely going to exist in its conjugate base form and its conjugate base form here is neutral. Now however we're not that far away though from pH seven with a pKa of six in this case anyways. And so as a result it means about 10% of the molecules would actually exist in the conjugate acid form and have a positive charge, 90% would look like this though and be neutral. But still if 10% of the molecules of the histidine residues I really should say in a protein kind of look like positively charged that still contributes a fair amount of overall positiveness into the structure if 10% of the molecules do or 10% of the residues do. Now one thing to note so here I've listed like pKa's and stuff like that that's just the free amino acid it turns out these pKa's when they're in the context of a larger protein often get modified a little bit depending on what else is in the area and stuff like that. So these pKa's are not set in stone the pKa's are just for the free amino acids but you definitely don't have to memorize them. So what you should take away here is that lysine arginine histine are basic amino acids and either often have a full positive charge or at least some partial positive charge in a protein. Alright finally we've got the acidic amino acids and the big thing to take away here is that they tend to have a negative charge at pH 7. So their pKa's are both right around 4 for the variable groups they're carboxylic acids. So and with a pKa of 4 well at pH 7 we're much more basic than that so they're going to largely exist in their conjugate base forms which are carboxylates and have a negative charge. And so we've got aspartic acid and glutamic acid so but the conjugate bases are called aspartate and glutamate and because of pH 7 at physiological pH they exist largely in their conjugate base form you know it's probably more proper to call them aspartate and glutamate. However what we're going to find out is we use them pretty interchangeably whether I say aspartate or aspartic acid and glutamate or glutamic acid treat them as synonymous in this context of protein. Also notice the difference between asparagene and aspartic acid aspartic acid or aspartate is a carboxylic acid or a carboxylate whereas asparagene was an amide instead. So and these are negatively charged whereas the amides with asparagene they were polar and cable hydrant bonding but they weren't charged. Cool. So the acidic ones are negatively charged at physiological pH and again we might find that some of these negatively charged acidic ones might be interacting with one of the basic positively charged ones in protein structure that plus minus interaction and things of this sort. So knowing which ones are acidic and basic of particular importance here. So now we're going to talk more about proteins themselves the polymers and again these are going to be chains of amino acids and typically we could be talking about you know dozens but more likely hundreds or even thousands of amino acids to compose a typical protein. We often think of proteins as enzymes and all enzymes are proteins excluding a very small subset of ribosymes where you've got RNA that can have some enzymatic activity but largely when we talk about enzymes in a biological context we're almost talking exclusively about proteins but not all proteins are enzymes we've got three other classes we want to group them into and we talk about structural proteins so things like your skin and your hair and stuff like that are built up of proteins and they're not catalyzing any reactions like an enzyme would they're just playing a structural role. You can also talk about the proteins of the cytoskeleton that make up like the microtubules and the microfilaments and things of this sort. Proteins that binding that are responsible for binding so we've got receptors on like the cell surface or in the nuclear surface and things of this sort and then you also got things like hemoglobin which binds oxygen. Motor proteins being the last class we'll talk about and this is like mice and motors that are walking along the actin and things of this sort transporting organelles and other things around this cell. So cool and those are the kind of the classes and you might be able to you know fit an extra class or break these up a little bit differently but these are kind of pretty standard four classes of proteins you might talk about. And finally we're going to talk about protein structure and it turns out we break up protein structure into a hierarchy of four classes if you will. That's primary structure, secondary structure, tertiary structure, quaternary structure. You might see primary you know labeled this way secondary like so tertiary like so, quaternary like so and we're just going to get kind of more complex and larger as we go up the chain here and so turns out a primary structure is just the amino acid sequence and we'll talk a little more about each of these in a second so but the amino acid sequence simply is the primary structure. Secondary structure is going to be some localized folding of these amino acids in very small regions of the protein and stuff like this and we're going to find out that these are all going to be mediated by hydrogen bonding in the backbone. So the variable R groups are not going to be involved in secondary structure. Tertiary structure, this is the overall three dimensional shape of a single polypeptide. So we'll find out that not all proteins are made up of a single polypeptide. Some are actually composed of multiple polypeptide chains interacting and stuff like this but how a single polypeptide folds up into its overall three dimensional shape that's called tertiary structure and it turns out all this is really important because we'd like to say that form determines function for a protein exactly the shape that it takes up determines what it can do and if it doesn't fold into the proper shape it won't carry out the proper function. And then finally, quaternary structure. This is the 3D shape of a protein composed of multiple subunits, multiple peptide chains. So like I kind of hinted to before so if you've got a protein that's composed of just a single polypeptide well it doesn't have quaternary structure but if you've got a protein that now is composed of multiple subunits, multiple polypeptides like say hemoglobin, hemoglobin is composed of four separate polypeptide chains and how they interact and come together that is called quaternary structure. Like I said, we'll talk a little more about each of these here in a sec and so we'll start with primary structure and again primary structure is just simply that sequence of amino acids that linear sequence of amino acids in a polypeptide and it turns out one thing you should know though is that all the necessary information for proper protein folding is contained within that primary structure within that amino acid sequence. So it turns out all the different interactions that when this protein folds up, all the different interactions that are possible, it turns out are totally a function of what that sequence of amino acids is. So we have lovely modeling programs that can determine what a protein might look like and they've gotten much much better at these predictions over time and the idea is that they're just going to minimize the energy so as this protein folds and ultimately it's going to achieve some sort of energy minimization that's why it folds into shape it does and that's all a function of what that amino acid sequence is. Next level of hierarchy in the structure here is the secondary structure and again, this is all about localized structures, localized elements and it's all held together by hydrogen bonding in the backbone super important. So again those variable R groups are not involved in secondary structure at all. So in the two most important types of secondary structure are going to be the alpha helix and the beta sheet. They're not the only two, they're other things like beta turns and stuff like this, but these are probably the only two you're likely to encounter on the DAT or the OAT. And let's take a look, we're going to find out what the alpha helix, we'll take a look at the structure in a second, that hydrogen bonding that takes place again within the backbone is parallel to the principal axis. So whereas with the beta sheets, we're going to find out that hydrogen bonding is going to be perpendicular to that principal axis, let's take a look. So here's an example of the structure of an alpha helix and we show them in the context of a broader protein structure, we often show the ribbon as kind of a way of representing proteins and stuff like that. When you see it in a right-handed coil like this, that's an alpha helix and sometimes they're short, sometimes they're long, they don't have to be super long to be considered an alpha helix. But if you notice what is holding it together here, so is hydrogen bonding within the backbone. The carbonyl oxygen of one amino acids interacting with the nitrin, the hydron, the nitrin, the amine nitrin of another amino acid and that's what actually holds this together and you can see that those run parallel to the axis of that alpha helix. So second type here is called the beta sheet and it turns out these can run one of two ways and you've got two sheets that are going to line up together and again if you were showing this in the broader context of a protein structure, we'd often show like ribbons so lined up parallel to each other hence the name and it turns out they can either be parallel or anti-parallel. So it turns out it's just running the same direction or opposite directions and it turns out we often can look at a protein based on so directionality and we look at the amino end and at one end of the protein there's going to be that free amino acid that's not part of an amide linkage and at the other end there's going to be a free carboxylic acid group that's not part of an amide linkage as well but again all the others are going to be in the interior parts of peptide bonds and amide linkages. Now we'll often refer to the end that is free.