Understanding Carbohydrates and Their Roles

So this is the beginning of exam three material, and we're going to move into the second class of biomolecules that we're going to study in this course, and that is carbohydrates. When we look at carbohydrates, these are the most abundant biological molecules. Oftentimes they're referred to as saccharides, which comes from the Greek word meaning sugar, and oftentimes you will see carbohydrates divided into two different groups. monosaccharides, which comprise the basic carbohydrate unit, which we call the simple sugars. Examples of that would be something like fructose or glucose. And then we have a second group which are called polysaccharides, where multiple monosaccharides are linked together. An example of that would be something like glycogen. When we look at the roles of carbohydrates, there are three major roles that these can play within the cell. Probably the first one of energy sources is what most people think of and that certainly is an important role, particularly when we think about the field of metabolism. But we're also going to see that carbohydrates play an important role as structural materials, as well as facilitating specific protein interactions. Now when we look at the classification of monosaccharides, these are the simple sugars, and this is where we're going to start for the first part of this lecture. Monosaccharides are classified according to the carbonyl group and the number of carbons. carbon atoms. The carbonyl group can either be part of an aldehyde or a ketone, and we separate these out in terms of referring to them as aldoses or ketoses. So aldoses are going to see a carbonyl group that are part of the aldehyde functional group, and a ketose is going to contain a ketone where the carbonyl group is part of that ketone structure. And then we have the number of carbons where three carbons would be considered a triose, four carbons, tetrose, five carbons, pentose. etc. When we look at how the atoms come together to allow for the forming of these saccharides, they're all composed of carbon, oxygen, and hydrogen. When we look at the formula, what we see is for every water molecule, there's a carbon. And when we look at N for the number of carbons, it's going to be three or greater, trioses or greater. Now, monosaccharides are classified according to the number of their carbons. So when we go back and we say a triose, that would mean N equals three. Therefore, we have... what would be three water molecules, so six hydrogens, three oxygen. Tetros is four carbons, so we have in that case eight hydrogens, four oxygens, or we could say four water molecules. When we look at monosaccharides, these are important to understand for the function and role that they play, but also an understanding that polymers of monosaccharides joined together are what form polysaccharides. So again, when we look at monosaccharides, we have two families. As a reminder, an aldose is going to contain the aldehyde group. You need to know those functional groups. So you have your carbonyl group bound to an R group and a hydrogen. And then we have ketoses that contain the ketone group. So in this case, our carbonyl is bound to two different R groups shown here as being methyls. So let's look at some examples of these. We can have glyceraldehyde. We could give its nomenclature as being an aldotriose. Aldo tells us that the carbonyl group shown here in pink. is going to be part of the aldehyde moiety. And the fact that it has three carbons makes it a triose, so an aldo triose. Dihydroxyacetone is considered a keto triose. We see the keto portion as our carbonyl is part of ketone functional group. And we say triose again because of three sugars. So how would we define each of these molecules shown here? The first one that we see We note that we have an aldehyde group, so that would make it an aldose. And we have one, two, three, four, five, six different carbons. So this would make it an aldohexose. The second group, we see that this is a ketose, and we see that we have one, two, three, four, five, six carbons. So we would call this a ketohexose. Turns out this aldohexose is D-glucose, and this ketohexose is D-fructose. Now when we talk about Fischer projections, again we have to bring up the fact that these are three-dimensional molecules that we oftentimes have to illustrate two-dimensionally, and we recognize that we have tetrahedral stereocenters. When we look at a D-monosaccharide using Fischer projections, this is going to show us that our OH group is going to be on the right hand side, and L-monosaccharide is going to have the OH group on the left hand side. When we look at monosaccharides, they contain one or more chiral carbons, and this means that there are active isomeric forms. So if we look here at a simple aldose, say sticking with glyceraldehyde, we see that we have one chiral carbon. And because of the stereochemistry about that chiral carbon, we have two possible isomeric forms with respect to the location of the OH group. If it's to the right, we call it the D form. If it's to the left, we call it the L form. A molecule with multiple chiral centers is going to have two possible stereocenters at each of those chiral carbons. Now, this is probably bringing up some more reminders from organic, where we talk about the term enantemers. Enantemers are a specific type of stereoisomers that are mirror images. So if we look at D and L glucose, and we were to put a mirror between these, we would see that they are the reflection of each other. They're not superimposable. One of the things that we have to define because of the fact that there can be multiple stereocenters is the fact that an epimer can exist. By definition, epimers are those monosaccharides that differ by the stereochemistry at one carbon atom. So let's look at our examples here. We have D-galactose, D-glucose, and D-mannose. First of all, how would we characterize all of these with respect to their overall structures? We see that these are all aldehyde-containing groups, so we would call those aldoses, and they all contain one, two, three, four, five, six carbons. So these are all examples of aldohexoses. So how do they differ? What are we looking about? Well, if we look at the difference between D-galactose and D-glucose, we see that their structure is identical except for at carbon-4. At carbon-4, we have the difference in stereochemistry specifically about that carbon. If we were to compare D-glucose and D-mannose, we would see that carbon 2 has the difference, that we have differences in stereocenters about carbon 2. So by definition, galactose and glucose are epimers, glucose and mannose are epimers. What can we say as to why galactose and mannose would not be considered epimers? In the case of the definition of an epimer, they can only differ in stereochemistry about one carbon. If you look at the difference between galactose and mannose, we see that they differ in stereochemistry about two carbons and therefore are not considered to be epimers. Now, this is an important table where you're going to need to learn important aldoses. And I have these shown in black boxes, and these are the ones that we're going to focus on for many of you that are going to be taking biochemistry at a later date, whether it's 4.11, professional school biochem, or you're studying for MCATs, PCATs, et cetera. I'm trying to pick for you the different... carbohydrates that you're going to see over and over again. So we have these divided out here. Pardon that slight interruption. So we have important aldoses that we're going to learn, and we have these already broken down based on the fact that they have the aldehyde functional groups in the aldo class, and then we divide them based on the number of carbons. Remember, triose means that we have three carbons. Petrose means that there are four carbons. Centoses mean five carbons and hexoses mean that there are six carbons. And when we look at the structures again in the black boxes, these are going to be the ones that we see more commonly metabolically playing important roles. And so these are going to be the structures that I'm going to require you to be able to recognize. We also did the same thing with important ketosis. Again, the structures that you must know, and we should know that each of these are containing of the ketone functional group. So we call these based on the identification of the carbonyl group, and the number of carbons. So ketotriose, ketotetrasis, ketopentosis, and ketohexis. When we look at aldoses and ketoses, it turns out these are easily interconverted. And picking an example, we have the glycolytic pathway or glycolysis. And if we look, we see an example right off the bat in how aldoses and ketosis can be interconverted. And so right here, I'm going to bring attention. We have GAP and its interconversion to DHAP. Those are glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. And it turns out that these are easily interconverted and it is part of the glycolytic pathway. This is characterized by an enzyme called triose phosphate isomerase. And remember, isomerases are those that catalyze isomerization reactions. And this occurs going through an intermediate that is called an endial intermediate. I want to point out endial intermediate. because of the double bond, all because of alcohol groups, and di meaning the fact that there are two OH groups. And this is oftentimes a characteristic of an isomerization reaction between aldoses and ketoses that are observed numerous times throughout metabolism. So we're going to look at drawing the mechanism of triose phosphate isomerase as we just got done looking at enzymes and the important role they play in catalytic pathways. and use this as an example to see how these monosaccharides can easily be interconverted. So when we look at the mechanism of triose phosphate isomerase, it's an example of general acid-base chemistry. So we see here that we start with an important glutamate residue, glutamate 165, and it's going to serve to be in the base form. It's going to trigger the reaction by abstracting a proton, going to the acid form. So we start here as a base, it abstracts the proton. And what this does is to help facilitate then the formation of the double bond. As the double bond is formed, we start to shift electrons into the oxygen. We know that that would form an oxyanion, and that is not. favorable in terms of energy. So what happens in this case is histidine serves as the acid. So it's going to have a proton that it's going to donate to the course of the reaction to help stabilize this intermediate. Notice this is where we have our ene and our two alcohol groups. Now what happens is histidyl is now in the basic form and it's going to abstract the proton from the other alcohol group. not the one that it just donated to, but instead abstract the proton from the other alcohol group, creating an oxyanion that is not stable. So it's going to reform the carbonyl group, and it's going to allow for glutamate then, serving as the acid, to abstract a proton and to essentially allow for the conversion of the carbonyl from carbon 2 to carbon 1, and we've now formed the aldehyde. An interesting thing about TPI, and I do want to put to sometimes your book calls it TIN as well, both abbreviations for triose phosphate isomerase, is it is an example of a catalytically perfect enzyme. And what this means is the rate of the bimolecular reaction between enzyme and substrate is diffusion controlled so that binding is always what is limiting. Chemistry cannot occur any quicker because the rate of the reaction is occurring, product formation is occurring as fastest substrate and enzyme collide. This is another reason that it makes it easy and accessible for the body to be able to interconvert aldoses and ketosis. When we look at aldoses and ketosis, it turns out that they actually can form cyclic structures. And these are because the reactivity of groups that they have found naturally within their structures and what the types of chemistry these functional groups prefer. So we have two important functional groups that can play an important role in this process. The carbonyl group we know has unequal sharing of electrons because of the partial negative charge of oxygen leaving the carbonyl carbon partial positive charge. And then of course, we have the alcohol groups and these are going to have a lone pair. Particularly when we look at a six-membered carbohydrate monosaccharide, we see that carbon-5 in particular's OH group can serve very well to do nucleophilic attack. and allow for the cyclic structure to form. We can call these gluco for glucose, pyranose because of the ring structure, and in this case they can be either in the alpha or the beta confirmation, depending upon the orientation of the OH group with respect to carbon 1. So how does this happen mechanistically? Well, it turns out that we call this type of chemistry the formation of either a hemiacetal or a hemiketal. The hemiacetal is the chemistry happening with the aldehyde, carbonyl carbon, and the hemiketal is going to involve the carbonyl carbon of a ketone. What happens here is we have the reaction between our electron-rich nucleophile and the fact that our carbonyl group has unequal sharing of electrons leaving a partially positive carbon. Again, this carbonyl can be part of an aldehyde group or it can be part of a ketone structure. And either way, we allow for the formation of the hemiacetal from the aldehyde cyclicization or hemiketal. from the ketone cyclicalization. This is the example of what happens for the cyclicalization of D-glucose in order to form glucopyranose. When we look at glucopyranose, when we look at this example, what we again see is our carbon one is what is containing our aldehyde functional group. We know that this is partial positive because of the oxygen being electronegative, carrying that partial negative charge. We then have our carbon five. And we see here we have our OH with this one pair that can serve well to do nucleophilic attack. And what ends up happening as we have free rotation about these single bonds is it will align so that the C5OH group will do nucleophilic attack to the carbonyl. This is cyclicization. And when we look at cyclicization and we talk about the fact that we have a six-membered ring, this is what we call the purine. So the six-membered ring is actually going to be five carbons. Notice that we have carbon one, two, three. four, five. And carbon six is pointing away from the ring structure. And the sixth member of the ring here is going to be forming with the oxygen. the OH group is served to do nucleophilic attack. And again, we can have either the alpha form, where we see our OH group is pointed in the opposite direction as our carbon six group, or we can have what's called the beta form. And this is where we see our OH group is pointed in the same orientation as our carbon six group. Now, when we look at how the cyclization occurs, a lot of times it's helpful to rely on those Fisher projections to kind of lay out on your form to look at how this bonds are being formed in cyclicization. So we see here our C5OH is what does nucleophilic attack to attach to our carbon one group. And again, depending upon the orientation of our carbon one, we can have it in the alpha or in the beta form. Now we also will see cyclization of six carbon containing ketoses. And this is an example for fructose. In this case, we have the exact same propensity for reactivity. It's just now our carbonyl is shifted to carbon 2 because of it being a ketone. And we still have the reactivity with our carbon 5 OH. And so we can have nucleophilic attack again. That occurs to allow for cyclization. The difference now is that we're going to have a five-membered ring. We have carbon 1 that's going to be pointed up. So the members of our ring are carbon 2, carbon 3, carbon 4. four, carbon five, and our oxygen from carbon five, sorry, carbon five. And so what we see then is we give rise to this furin ring structure. Again, you have one, two, three, four carbons, and the fifth member is the oxygen. Just like we saw for the civilization of glucose, what we see with fructofuranose is that we can again have the orientation, and this time at carbon two, where the ring closure has occurred by the formation of that new. nucleophilic attack. If the OH group is pointed in the opposite direction as our carbon 6 group, we call that the alpha form. If we have our OH group pointed in the same orientation as our carbon 6 group, we call that the beta form. And again, we can look at Fisher projections where we see our ketone group carbonyl carbon 2 nucleophilic attack by C5OH. That's what's going to allow for cyclotization. And then we just look at the orientation with respect to C2OH as being in the alpha or the beta conformation. So when we look at the names, we use, in terms of talking about glucopyrinose or fructopyrinose, it's based on the members of the ring. So again, a pyrin is going to have one, two, three, four, five carbons, and six members are going to make up from the oxygen. And the furin is going to have one, two, three, four carbons, and the fifth member is going to be made up of the oxygen. So we use this as part of nomenclature to indicate the fact that indeed these monosaccharides are cyclized. So anytime we have a six-membered ring, we call those furinose. Anytime we have a five-membered ring, we call those furinose. And that's because of the basic structure of the furin and furin rings. Now, one of the things you may notice is based on the... type of chemistry that's happening between the alcohol group serving as a nucleophile with the carbonyl, that there's a possibility of multiple cyclicizations. In many monosaccharides, there are two or more reactive hydroxyl groups that can serve to do this attack, facilitating this OH nucleophilic attack. So if we look here with glucose, if we were to look at the fact that we could have forming a five-membered ring, a furanose form. That would mean the C4OH group does nucleophilic attack, so C4, or we have our C5 doing nucleophilic attack and would allow for the six-membered ring or the furanose form. With ribose, when we look at this structure, we see that it has the ability to allow for C5 or C6, forming a furanose structure and a furanose structure, respectively. So the idea is if there are two or more reactive hydroxyl groups, we would have multiple cyclicization products. Reality is that the nature of the substituents on the carbonyl and the hydroxyl groups, as well as the nature of the asymmetric carbons, determines energetically whether the pyranose versus pyranose ring form is favored. Turns out that aldohexoses, I think glucose, these sugars are always going to prefer the six-membered ring and will take on pyranose structure. energetically more stable, what we observe, and ketohexose sugars are going to prefer the furanose structure five-membered ring. When we go back and we look at these rings, we also have to think about conformations. So again, some of that organic coming back where we talk about the boat versus the chair. When we look at these conformations, we know that based on spacing and energetic stability that the chair conformation is favored. We can also look here at our alpha glucose versus our beta form of our glucose in the chair conformation. What other things have to be considered when we look at these ring structures in a chair conformation? This is going to be the fact that they're not planar. And what we have is the ability to allow for these different substituents to be either in the equatorial or axial position. If we think about stability, the fact that we have all these OHs pointed towards the same orientation is going to mean that they are closer together and therefore potentially not going to be as happy in terms of structure. So this is not as stable. Instead, what we see is that the more stable structure is going to form. Therefore, the confirmation of beta-D-glucose the most widely occurring organic group in all of nature, as well as being the central hexose and carbohydrate metabolite, is going to prefer to be in the equatorial boat conformation. So this, I'm sorry, chair conformation. So this chair conformation is what we're going to see in the equatorial position for beta D glucopyranose. Now when we look at monosaccharides, these can be converted to several different derivative forms. And this is important because different derivatives are going to have different unique functions within the cell. Some of the ways that we can allow for chemical reactions and enzymatic reactions to produce derivatives are going to allow for the production of sugar acids, sugar alcohols, deoxysugars, sugar esters, amino sugars, acetal, ketals, and glycosides. Now, we're not necessarily going to cover every single one of those, but what I want to walk through and do is to give you some examples of how these different derivatives can form. and some of the functions that we're going to see for these different sugar modifications. So monosaccharides can be converted to different forms. When we look here at our aldehyde group, we realize that this is capable of being oxidized, losing electrons, and being converted to the functional group where we look here of a carboxylic acid. So at C1 position, we're going to see glucose can be converted to... what is called gluconic acid. And gluconic acid is susceptible to ring closure, and we call these gluconolactones. It's actually one of the molecules that we'll see in the pentose phosphate pathway. We can also have oxidation at carbon-6. Carbon-6 is taking an alcohol, and it can allow for it to be oxidized to a carboxylic acid. And we see here the formation of glucuronic acid. Glucuronic acid can also cyclize, and we have D-glucuronic acid in what we call D-iduronic acid, depending upon the orientation with respect to that oxidized alcohol group that becomes D-carboxylic acid. If we have oxidation at carbon 1 and carbon 6, we call this glucaric acid. So both the aldehyde and the alcohol group have been oxidized. When we look at sugar derivatives, again, these are going to undergo reactions that are typical of aldehydes and ketones, and they have important physiological consequences. Oxidation of aldehydes produce carboxylic acids. Oxidation of primary alcohols yield uronic acids, and we can also have reductions where a gain of electrons, and this is going to allow for aldoses and ketoses to produce ribotols and hydroxyl groups to be replaced by hydrogen. The other thing that we also can see is that sugars contain carbons, hydrogen, and oxygen. But through amination reactions, we also have the ability of replacing alcohol groups with amine groups, which can also introduce nitrogens. And this becomes important in terms of linkages, particularly when we start thinking about the fact that these carbohydrates can modify lipids and protein structures in terms of allowing for different cellular functions. So when we look at sugar derivatives... We have the gluconic and the glucuronic acids. So oxidation of the aldehyde group is going to be what we call an aldonic acid in the name based in the onic acid. We can have oxidation of the primary alcohol group, and this is going to make what's called uronic acid, and uronic is fixed at the end. These can each have unique functions. Glucuronic acid is actually one of the major uses that we will see that happens within your kidneys. where certain things that are insoluble and therefore are not readily excretable in urine can allow for the conversion of glucose to D-glucuronic acid. And glucuronic acid can then tag insoluble molecules in order to make them soluble so that your body has a way to excrete them. I always like to bring up, we know the importance of the fact that we have within our body a way of losing weight, of really limiting carbohydrates in our diet, and that's going to put your body into fat-burning mode using fat as an energy source in a very popular diet. One of the things that has shown to be issues are people that are either prone to kidney issues or follow the diet so extensively that their body is always starved for sugars. that what will happen is that your body will siphon off glucose that should go to the kidneys for the process of glucuronidation. And instead, it's going to use it in other ways. Like I said, your brain functions on glucose. And what happens is there starts to become kidney issues because people with the lack of glucuronic acid start to have buildup of insoluble molecules that are not being properly excreted. These can cause things like kidney issues and also cause problems in terms of healthy kidney function. The other thing that we can have is reduction. So reduction, remember, is the gain of electrons. And we can have an aldehyde that by picking up electrons can actually serve to be reduced to form the functional group of an alcohol. When we look at sugar alcohols, there's ribotol becomes important building block in cofactors. One of those is the flavins. So we talk about the importance of oxidation reduction reactions. Flavins are cofactors that are more involved in redox reactions. We have xylitol, maybe you've heard of this as a sweetener in sugarless gum and candies. And then we have glycerol and myonestetol, which we are going to see are incredibly important components as we start to look at lipids. Now xylitol is a unique one. We use this as sugarless gum, but one of the things I always like to bring up with it is xylitol metabolism can differ between species. It does not show to be harmful to humans. However, this can be incredibly deadly for dogs. So really watch that your animals don't get into this. It actually causes two major things to happen. The first is it can spike blood sugar, come crashing down. Those changes can lead to seizures. And secondly, it causes damage to their liver. It's reported that enzymes, protein function associated with the liver, actually gets released into the blood. stream because of the damage to the liver and that can also be monitored where it can impact their liver function. As a matter of fact, we are very involved in dog rescue and we have foster dogs through Urgent Animals of Hearn. If you've ever heard of that group and like dogs, they're amazing. And we had a, we'll call her a hard keeper named Molly. Maybe in one of my next videos, I'll show y'all a picture of Molly. The sweetest dog in the whole wide world has very few boundaries, is into everything all the time. And we ended up keeping her because we love her. She's a precious dog, but she gets into everything. And one day she was on our kitchen counter. I know not what we train her to do, but she's very agile, little rat terrier dog. And she got into melatonin. And I didn't even notice it. My son, who was like five at a time, was like, oh, the dog is eating something. So anyway, I called the poison control and she had eaten a decent amount of this melatonin. So I went ahead and through the advice of vets, gave her some stuff to allow her to vomit and get it up. And when I was talking to the people, it's really cool, through Austin Human Quality, can ask any questions to their vet services, they said there wasn't anything that was bad about melatonin that had been on record. They didn't know. But that particular type of melatonin was a rapid release that had high amounts of xylitol flavoring. So they recommended that we immediately get her to the local... a vet, closest local vet, which ended up being A&M's small animal clinic. And so they were able to monitor her and she did have liver damage. We had to put her on some medication for about a month or so, but hers was pretty minimal because of the fact that we were able to have her throw up those pills and not really ingest it. And we had one of the young vets that walked out and he was like, oh, she's the sweetest dog in the world. We're like, yes, thank you. We pay you a thousand dollars for saving her life because she won't stay out of counters and eating stuff. But we were very relieved she was okay and he had told us that just a couple weeks earlier somebody had brought in a puppy that had gotten hold of sugarless gum and ate packets of gum and the dog ended up making it but its liver had been aged significantly for being just a puppy. So the reason we warn this is because we don't always know if it's additives, what it does to other species. Xylitol is a big one that's shown to be very deadly. And also to point out to the fact that unfortunately they're starting to put it in peanut butters and a lot of people will pill their dogs by putting it in peanut butter first, help them eat their medication. So also be very, very careful of that. The last one we're going to talk about is amination, and I'm going to introduce this because to get into our polysaccharide unit, we're going to see the importance of the addition of the amine group. And when we look at these glycoproteins, the attachment of sugar to protein molecules or the attachment of sugars to lipids, one of the things that we also oftentimes will see is those amine groups become important attachment points. So glucosamine or galactosamine are two of the simple sugars that have been modified by replacing an OH group. with that amine, so-called amination reactions. And there are many possible functions, again, that we're going to see with the amination reactions. We can add them to enzymes to influence their function. Transport proteins are oftentimes going to be modified with sugars. Receptors, we've talked a little bit about the receptor on a cell and its interaction with the hormone. Amination can help allow for connection points of the sugars to the receptors that help build specificity for our hormone bind. as well as the role that they can have in structural proteins. And we're going to see this soon enough with the function of the polysaccharide chitin in the structural role that it has. So again, when we look at the cyclicization of carbohydrates and the reaction that occurs between the hydroxyl end and a carbonyl of either the aldehyde or ketone, and we go through the cyclicization process. Again, monosaccharides are going to cyclize to form the most stable structure. The furin form is going to have... five-membered ring, purine is going to have six-membered ring, and we see that these are going to favor the cyclic structure within the cell. And again, we talked about the alpha-beta form. Generally, we say the alpha-C1OH is going to be down opposite of the C6 pointing up, and generally, we're going to see that the beta form is going to be pointed up OH in the same direction as the carbon-6-4. So this brings to the example then the importance of the anomeric carbon. And the anomeric carbon is what we call the cyclicization carbon, where the chemistry occurred to allow for the cyclic structure. It's the carbonyl carbon that's used in cyclic formation. And because of the fact that we differ in the OH orientation about that anomeric carbon, we call these structures in the alpha-glucopyrinose versus the beta-glucopyrinose form, we call these anomers. Important nature of the anomeric carbon, we're going to see as it relates to glycosidic bond formation. So remember, when we talk about carbohydrates, we talked about the two classification monosaccharides, which are the simple sugars, but also to form polysaccharides. A lot of times if there's two, we'll call them disaccharides, but polysaccharides and disaccharides are multiple monosaccharides joined together. And we're going to see the critical role that anomeric carbons are going to play in facilitating the chemistry of the glycosidic bond. that allow for monosaccharides to be joined together. So we're going to stop here, and we're going to pick up in part two as we get into our polysaccharides.

monosaccharides, which comprise the basic carbohydrate unit, which we call the simple sugars. Examples of that would be something like fructose or glucose. And then we have a second group which are called polysaccharides, where multiple monosaccharides are linked together. An example of that would be something like glycogen.

When we look at the roles of carbohydrates, there are three major roles that these can play within the cell. Probably the first one of energy sources is what most people think of and that certainly is an important role, particularly when we think about the field of metabolism. But we're also going to see that carbohydrates play an important role as structural materials, as well as facilitating specific protein interactions. Now when we look at the classification of monosaccharides, these are the simple sugars, and this is where we're going to start for the first part of this lecture.

Monosaccharides are classified according to the carbonyl group and the number of carbons. carbon atoms. The carbonyl group can either be part of an aldehyde or a ketone, and we separate these out in terms of referring to them as aldoses or ketoses. So aldoses are going to see a carbonyl group that are part of the aldehyde functional group, and a ketose is going to contain a ketone where the carbonyl group is part of that ketone structure. And then we have the number of carbons where three carbons would be considered a triose, four carbons, tetrose, five carbons, pentose.

etc. When we look at how the atoms come together to allow for the forming of these saccharides, they're all composed of carbon, oxygen, and hydrogen. When we look at the formula, what we see is for every water molecule, there's a carbon.

And when we look at N for the number of carbons, it's going to be three or greater, trioses or greater. Now, monosaccharides are classified according to the number of their carbons. So when we go back and we say a triose, that would mean N equals three. Therefore, we have... what would be three water molecules, so six hydrogens, three oxygen.

Tetros is four carbons, so we have in that case eight hydrogens, four oxygens, or we could say four water molecules. When we look at monosaccharides, these are important to understand for the function and role that they play, but also an understanding that polymers of monosaccharides joined together are what form polysaccharides. So again, when we look at monosaccharides, we have two families. As a reminder, an aldose is going to contain the aldehyde group.

You need to know those functional groups. So you have your carbonyl group bound to an R group and a hydrogen. And then we have ketoses that contain the ketone group. So in this case, our carbonyl is bound to two different R groups shown here as being methyls.

So let's look at some examples of these. We can have glyceraldehyde. We could give its nomenclature as being an aldotriose.

Aldo tells us that the carbonyl group shown here in pink. is going to be part of the aldehyde moiety. And the fact that it has three carbons makes it a triose, so an aldo triose. Dihydroxyacetone is considered a keto triose. We see the keto portion as our carbonyl is part of ketone functional group.

And we say triose again because of three sugars. So how would we define each of these molecules shown here? The first one that we see We note that we have an aldehyde group, so that would make it an aldose.

And we have one, two, three, four, five, six different carbons. So this would make it an aldohexose. The second group, we see that this is a ketose, and we see that we have one, two, three, four, five, six carbons.

So we would call this a ketohexose. Turns out this aldohexose is D-glucose, and this ketohexose is D-fructose. Now when we talk about Fischer projections, again we have to bring up the fact that these are three-dimensional molecules that we oftentimes have to illustrate two-dimensionally, and we recognize that we have tetrahedral stereocenters. When we look at a D-monosaccharide using Fischer projections, this is going to show us that our OH group is going to be on the right hand side, and L-monosaccharide is going to have the OH group on the left hand side.

When we look at monosaccharides, they contain one or more chiral carbons, and this means that there are active isomeric forms. So if we look here at a simple aldose, say sticking with glyceraldehyde, we see that we have one chiral carbon. And because of the stereochemistry about that chiral carbon, we have two possible isomeric forms with respect to the location of the OH group.

If it's to the right, we call it the D form. If it's to the left, we call it the L form. A molecule with multiple chiral centers is going to have two possible stereocenters at each of those chiral carbons. Now, this is probably bringing up some more reminders from organic, where we talk about the term enantemers.

Enantemers are a specific type of stereoisomers that are mirror images. So if we look at D and L glucose, and we were to put a mirror between these, we would see that they are the reflection of each other. They're not superimposable.

One of the things that we have to define because of the fact that there can be multiple stereocenters is the fact that an epimer can exist. By definition, epimers are those monosaccharides that differ by the stereochemistry at one carbon atom. So let's look at our examples here. We have D-galactose, D-glucose, and D-mannose. First of all, how would we characterize all of these with respect to their overall structures?

We see that these are all aldehyde-containing groups, so we would call those aldoses, and they all contain one, two, three, four, five, six carbons. So these are all examples of aldohexoses. So how do they differ? What are we looking about?

Well, if we look at the difference between D-galactose and D-glucose, we see that their structure is identical except for at carbon-4. At carbon-4, we have the difference in stereochemistry specifically about that carbon. If we were to compare D-glucose and D-mannose, we would see that carbon 2 has the difference, that we have differences in stereocenters about carbon 2. So by definition, galactose and glucose are epimers, glucose and mannose are epimers.

What can we say as to why galactose and mannose would not be considered epimers? In the case of the definition of an epimer, they can only differ in stereochemistry about one carbon. If you look at the difference between galactose and mannose, we see that they differ in stereochemistry about two carbons and therefore are not considered to be epimers. Now, this is an important table where you're going to need to learn important aldoses.

And I have these shown in black boxes, and these are the ones that we're going to focus on for many of you that are going to be taking biochemistry at a later date, whether it's 4.11, professional school biochem, or you're studying for MCATs, PCATs, et cetera. I'm trying to pick for you the different... carbohydrates that you're going to see over and over again.

So we have these divided out here. Pardon that slight interruption. So we have important aldoses that we're going to learn, and we have these already broken down based on the fact that they have the aldehyde functional groups in the aldo class, and then we divide them based on the number of carbons. Remember, triose means that we have three carbons.

Petrose means that there are four carbons. Centoses mean five carbons and hexoses mean that there are six carbons. And when we look at the structures again in the black boxes, these are going to be the ones that we see more commonly metabolically playing important roles.

And so these are going to be the structures that I'm going to require you to be able to recognize. We also did the same thing with important ketosis. Again, the structures that you must know, and we should know that each of these are containing of the ketone functional group.

So we call these based on the identification of the carbonyl group, and the number of carbons. So ketotriose, ketotetrasis, ketopentosis, and ketohexis. When we look at aldoses and ketoses, it turns out these are easily interconverted. And picking an example, we have the glycolytic pathway or glycolysis. And if we look, we see an example right off the bat in how aldoses and ketosis can be interconverted.

And so right here, I'm going to bring attention. We have GAP and its interconversion to DHAP. Those are glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. And it turns out that these are easily interconverted and it is part of the glycolytic pathway. This is characterized by an enzyme called triose phosphate isomerase.

And remember, isomerases are those that catalyze isomerization reactions. And this occurs going through an intermediate that is called an endial intermediate. I want to point out endial intermediate.

because of the double bond, all because of alcohol groups, and di meaning the fact that there are two OH groups. And this is oftentimes a characteristic of an isomerization reaction between aldoses and ketoses that are observed numerous times throughout metabolism. So we're going to look at drawing the mechanism of triose phosphate isomerase as we just got done looking at enzymes and the important role they play in catalytic pathways.

and use this as an example to see how these monosaccharides can easily be interconverted. So when we look at the mechanism of triose phosphate isomerase, it's an example of general acid-base chemistry. So we see here that we start with an important glutamate residue, glutamate 165, and it's going to serve to be in the base form.

It's going to trigger the reaction by abstracting a proton, going to the acid form. So we start here as a base, it abstracts the proton. And what this does is to help facilitate then the formation of the double bond.

As the double bond is formed, we start to shift electrons into the oxygen. We know that that would form an oxyanion, and that is not. favorable in terms of energy. So what happens in this case is histidine serves as the acid.

So it's going to have a proton that it's going to donate to the course of the reaction to help stabilize this intermediate. Notice this is where we have our ene and our two alcohol groups. Now what happens is histidyl is now in the basic form and it's going to abstract the proton from the other alcohol group. not the one that it just donated to, but instead abstract the proton from the other alcohol group, creating an oxyanion that is not stable. So it's going to reform the carbonyl group, and it's going to allow for glutamate then, serving as the acid, to abstract a proton and to essentially allow for the conversion of the carbonyl from carbon 2 to carbon 1, and we've now formed the aldehyde.

An interesting thing about TPI, and I do want to put to sometimes your book calls it TIN as well, both abbreviations for triose phosphate isomerase, is it is an example of a catalytically perfect enzyme. And what this means is the rate of the bimolecular reaction between enzyme and substrate is diffusion controlled so that binding is always what is limiting. Chemistry cannot occur any quicker because the rate of the reaction is occurring, product formation is occurring as fastest substrate and enzyme collide. This is another reason that it makes it easy and accessible for the body to be able to interconvert aldoses and ketosis.

When we look at aldoses and ketosis, it turns out that they actually can form cyclic structures. And these are because the reactivity of groups that they have found naturally within their structures and what the types of chemistry these functional groups prefer. So we have two important functional groups that can play an important role in this process. The carbonyl group we know has unequal sharing of electrons because of the partial negative charge of oxygen leaving the carbonyl carbon partial positive charge. And then of course, we have the alcohol groups and these are going to have a lone pair.

Particularly when we look at a six-membered carbohydrate monosaccharide, we see that carbon-5 in particular's OH group can serve very well to do nucleophilic attack. and allow for the cyclic structure to form. We can call these gluco for glucose, pyranose because of the ring structure, and in this case they can be either in the alpha or the beta confirmation, depending upon the orientation of the OH group with respect to carbon 1. So how does this happen mechanistically? Well, it turns out that we call this type of chemistry the formation of either a hemiacetal or a hemiketal.

The hemiacetal is the chemistry happening with the aldehyde, carbonyl carbon, and the hemiketal is going to involve the carbonyl carbon of a ketone. What happens here is we have the reaction between our electron-rich nucleophile and the fact that our carbonyl group has unequal sharing of electrons leaving a partially positive carbon. Again, this carbonyl can be part of an aldehyde group or it can be part of a ketone structure.

And either way, we allow for the formation of the hemiacetal from the aldehyde cyclicization or hemiketal. from the ketone cyclicalization. This is the example of what happens for the cyclicalization of D-glucose in order to form glucopyranose. When we look at glucopyranose, when we look at this example, what we again see is our carbon one is what is containing our aldehyde functional group.

We know that this is partial positive because of the oxygen being electronegative, carrying that partial negative charge. We then have our carbon five. And we see here we have our OH with this one pair that can serve well to do nucleophilic attack.

And what ends up happening as we have free rotation about these single bonds is it will align so that the C5OH group will do nucleophilic attack to the carbonyl. This is cyclicization. And when we look at cyclicization and we talk about the fact that we have a six-membered ring, this is what we call the purine. So the six-membered ring is actually going to be five carbons. Notice that we have carbon one, two, three.

four, five. And carbon six is pointing away from the ring structure. And the sixth member of the ring here is going to be forming with the oxygen.

the OH group is served to do nucleophilic attack. And again, we can have either the alpha form, where we see our OH group is pointed in the opposite direction as our carbon six group, or we can have what's called the beta form. And this is where we see our OH group is pointed in the same orientation as our carbon six group. Now, when we look at how the cyclization occurs, a lot of times it's helpful to rely on those Fisher projections to kind of lay out on your form to look at how this bonds are being formed in cyclicization. So we see here our C5OH is what does nucleophilic attack to attach to our carbon one group.

And again, depending upon the orientation of our carbon one, we can have it in the alpha or in the beta form. Now we also will see cyclization of six carbon containing ketoses. And this is an example for fructose.

In this case, we have the exact same propensity for reactivity. It's just now our carbonyl is shifted to carbon 2 because of it being a ketone. And we still have the reactivity with our carbon 5 OH. And so we can have nucleophilic attack again.

That occurs to allow for cyclization. The difference now is that we're going to have a five-membered ring. We have carbon 1 that's going to be pointed up. So the members of our ring are carbon 2, carbon 3, carbon 4. four, carbon five, and our oxygen from carbon five, sorry, carbon five. And so what we see then is we give rise to this furin ring structure.

Again, you have one, two, three, four carbons, and the fifth member is the oxygen. Just like we saw for the civilization of glucose, what we see with fructofuranose is that we can again have the orientation, and this time at carbon two, where the ring closure has occurred by the formation of that new. nucleophilic attack.

If the OH group is pointed in the opposite direction as our carbon 6 group, we call that the alpha form. If we have our OH group pointed in the same orientation as our carbon 6 group, we call that the beta form. And again, we can look at Fisher projections where we see our ketone group carbonyl carbon 2 nucleophilic attack by C5OH.

That's what's going to allow for cyclotization. And then we just look at the orientation with respect to C2OH as being in the alpha or the beta conformation. So when we look at the names, we use, in terms of talking about glucopyrinose or fructopyrinose, it's based on the members of the ring. So again, a pyrin is going to have one, two, three, four, five carbons, and six members are going to make up from the oxygen.

And the furin is going to have one, two, three, four carbons, and the fifth member is going to be made up of the oxygen. So we use this as part of nomenclature to indicate the fact that indeed these monosaccharides are cyclized. So anytime we have a six-membered ring, we call those furinose. Anytime we have a five-membered ring, we call those furinose. And that's because of the basic structure of the furin and furin rings.

Now, one of the things you may notice is based on the... type of chemistry that's happening between the alcohol group serving as a nucleophile with the carbonyl, that there's a possibility of multiple cyclicizations. In many monosaccharides, there are two or more reactive hydroxyl groups that can serve to do this attack, facilitating this OH nucleophilic attack. So if we look here with glucose, if we were to look at the fact that we could have forming a five-membered ring, a furanose form. That would mean the C4OH group does nucleophilic attack, so C4, or we have our C5 doing nucleophilic attack and would allow for the six-membered ring or the furanose form.

With ribose, when we look at this structure, we see that it has the ability to allow for C5 or C6, forming a furanose structure and a furanose structure, respectively. So the idea is if there are two or more reactive hydroxyl groups, we would have multiple cyclicization products. Reality is that the nature of the substituents on the carbonyl and the hydroxyl groups, as well as the nature of the asymmetric carbons, determines energetically whether the pyranose versus pyranose ring form is favored.

Turns out that aldohexoses, I think glucose, these sugars are always going to prefer the six-membered ring and will take on pyranose structure. energetically more stable, what we observe, and ketohexose sugars are going to prefer the furanose structure five-membered ring. When we go back and we look at these rings, we also have to think about conformations. So again, some of that organic coming back where we talk about the boat versus the chair. When we look at these conformations, we know that based on spacing and energetic stability that the chair conformation is favored.

We can also look here at our alpha glucose versus our beta form of our glucose in the chair conformation. What other things have to be considered when we look at these ring structures in a chair conformation? This is going to be the fact that they're not planar. And what we have is the ability to allow for these different substituents to be either in the equatorial or axial position.

If we think about stability, the fact that we have all these OHs pointed towards the same orientation is going to mean that they are closer together and therefore potentially not going to be as happy in terms of structure. So this is not as stable. Instead, what we see is that the more stable structure is going to form.

Therefore, the confirmation of beta-D-glucose the most widely occurring organic group in all of nature, as well as being the central hexose and carbohydrate metabolite, is going to prefer to be in the equatorial boat conformation. So this, I'm sorry, chair conformation. So this chair conformation is what we're going to see in the equatorial position for beta D glucopyranose.

Now when we look at monosaccharides, these can be converted to several different derivative forms. And this is important because different derivatives are going to have different unique functions within the cell. Some of the ways that we can allow for chemical reactions and enzymatic reactions to produce derivatives are going to allow for the production of sugar acids, sugar alcohols, deoxysugars, sugar esters, amino sugars, acetal, ketals, and glycosides. Now, we're not necessarily going to cover every single one of those, but what I want to walk through and do is to give you some examples of how these different derivatives can form. and some of the functions that we're going to see for these different sugar modifications.

So monosaccharides can be converted to different forms. When we look here at our aldehyde group, we realize that this is capable of being oxidized, losing electrons, and being converted to the functional group where we look here of a carboxylic acid. So at C1 position, we're going to see glucose can be converted to... what is called gluconic acid.

And gluconic acid is susceptible to ring closure, and we call these gluconolactones. It's actually one of the molecules that we'll see in the pentose phosphate pathway. We can also have oxidation at carbon-6. Carbon-6 is taking an alcohol, and it can allow for it to be oxidized to a carboxylic acid.

And we see here the formation of glucuronic acid. Glucuronic acid can also cyclize, and we have D-glucuronic acid in what we call D-iduronic acid, depending upon the orientation with respect to that oxidized alcohol group that becomes D-carboxylic acid. If we have oxidation at carbon 1 and carbon 6, we call this glucaric acid. So both the aldehyde and the alcohol group have been oxidized.

When we look at sugar derivatives, again, these are going to undergo reactions that are typical of aldehydes and ketones, and they have important physiological consequences. Oxidation of aldehydes produce carboxylic acids. Oxidation of primary alcohols yield uronic acids, and we can also have reductions where a gain of electrons, and this is going to allow for aldoses and ketoses to produce ribotols and hydroxyl groups to be replaced by hydrogen. The other thing that we also can see is that sugars contain carbons, hydrogen, and oxygen.

But through amination reactions, we also have the ability of replacing alcohol groups with amine groups, which can also introduce nitrogens. And this becomes important in terms of linkages, particularly when we start thinking about the fact that these carbohydrates can modify lipids and protein structures in terms of allowing for different cellular functions. So when we look at sugar derivatives...

We have the gluconic and the glucuronic acids. So oxidation of the aldehyde group is going to be what we call an aldonic acid in the name based in the onic acid. We can have oxidation of the primary alcohol group, and this is going to make what's called uronic acid, and uronic is fixed at the end. These can each have unique functions. Glucuronic acid is actually one of the major uses that we will see that happens within your kidneys.

where certain things that are insoluble and therefore are not readily excretable in urine can allow for the conversion of glucose to D-glucuronic acid. And glucuronic acid can then tag insoluble molecules in order to make them soluble so that your body has a way to excrete them. I always like to bring up, we know the importance of the fact that we have within our body a way of losing weight, of really limiting carbohydrates in our diet, and that's going to put your body into fat-burning mode using fat as an energy source in a very popular diet. One of the things that has shown to be issues are people that are either prone to kidney issues or follow the diet so extensively that their body is always starved for sugars.

that what will happen is that your body will siphon off glucose that should go to the kidneys for the process of glucuronidation. And instead, it's going to use it in other ways. Like I said, your brain functions on glucose.

And what happens is there starts to become kidney issues because people with the lack of glucuronic acid start to have buildup of insoluble molecules that are not being properly excreted. These can cause things like kidney issues and also cause problems in terms of healthy kidney function. The other thing that we can have is reduction.

So reduction, remember, is the gain of electrons. And we can have an aldehyde that by picking up electrons can actually serve to be reduced to form the functional group of an alcohol. When we look at sugar alcohols, there's ribotol becomes important building block in cofactors. One of those is the flavins.

So we talk about the importance of oxidation reduction reactions. Flavins are cofactors that are more involved in redox reactions. We have xylitol, maybe you've heard of this as a sweetener in sugarless gum and candies. And then we have glycerol and myonestetol, which we are going to see are incredibly important components as we start to look at lipids. Now xylitol is a unique one.

We use this as sugarless gum, but one of the things I always like to bring up with it is xylitol metabolism can differ between species. It does not show to be harmful to humans. However, this can be incredibly deadly for dogs.

So really watch that your animals don't get into this. It actually causes two major things to happen. The first is it can spike blood sugar, come crashing down. Those changes can lead to seizures. And secondly, it causes damage to their liver.

It's reported that enzymes, protein function associated with the liver, actually gets released into the blood. stream because of the damage to the liver and that can also be monitored where it can impact their liver function. As a matter of fact, we are very involved in dog rescue and we have foster dogs through Urgent Animals of Hearn.

If you've ever heard of that group and like dogs, they're amazing. And we had a, we'll call her a hard keeper named Molly. Maybe in one of my next videos, I'll show y'all a picture of Molly. The sweetest dog in the whole wide world has very few boundaries, is into everything all the time. And we ended up keeping her because we love her.

She's a precious dog, but she gets into everything. And one day she was on our kitchen counter. I know not what we train her to do, but she's very agile, little rat terrier dog. And she got into melatonin.

And I didn't even notice it. My son, who was like five at a time, was like, oh, the dog is eating something. So anyway, I called the poison control and she had eaten a decent amount of this melatonin. So I went ahead and through the advice of vets, gave her some stuff to allow her to vomit and get it up. And when I was talking to the people, it's really cool, through Austin Human Quality, can ask any questions to their vet services, they said there wasn't anything that was bad about melatonin that had been on record.

They didn't know. But that particular type of melatonin was a rapid release that had high amounts of xylitol flavoring. So they recommended that we immediately get her to the local... a vet, closest local vet, which ended up being A&M's small animal clinic. And so they were able to monitor her and she did have liver damage.

We had to put her on some medication for about a month or so, but hers was pretty minimal because of the fact that we were able to have her throw up those pills and not really ingest it. And we had one of the young vets that walked out and he was like, oh, she's the sweetest dog in the world. We're like, yes, thank you. We pay you a thousand dollars for saving her life because she won't stay out of counters and eating stuff. But we were very relieved she was okay and he had told us that just a couple weeks earlier somebody had brought in a puppy that had gotten hold of sugarless gum and ate packets of gum and the dog ended up making it but its liver had been aged significantly for being just a puppy.

So the reason we warn this is because we don't always know if it's additives, what it does to other species. Xylitol is a big one that's shown to be very deadly. And also to point out to the fact that unfortunately they're starting to put it in peanut butters and a lot of people will pill their dogs by putting it in peanut butter first, help them eat their medication.

So also be very, very careful of that. The last one we're going to talk about is amination, and I'm going to introduce this because to get into our polysaccharide unit, we're going to see the importance of the addition of the amine group. And when we look at these glycoproteins, the attachment of sugar to protein molecules or the attachment of sugars to lipids, one of the things that we also oftentimes will see is those amine groups become important attachment points.

So glucosamine or galactosamine are two of the simple sugars that have been modified by replacing an OH group. with that amine, so-called amination reactions. And there are many possible functions, again, that we're going to see with the amination reactions. We can add them to enzymes to influence their function. Transport proteins are oftentimes going to be modified with sugars.

Receptors, we've talked a little bit about the receptor on a cell and its interaction with the hormone. Amination can help allow for connection points of the sugars to the receptors that help build specificity for our hormone bind. as well as the role that they can have in structural proteins.

And we're going to see this soon enough with the function of the polysaccharide chitin in the structural role that it has. So again, when we look at the cyclicization of carbohydrates and the reaction that occurs between the hydroxyl end and a carbonyl of either the aldehyde or ketone, and we go through the cyclicization process. Again, monosaccharides are going to cyclize to form the most stable structure. The furin form is going to have... five-membered ring, purine is going to have six-membered ring, and we see that these are going to favor the cyclic structure within the cell.

And again, we talked about the alpha-beta form. Generally, we say the alpha-C1OH is going to be down opposite of the C6 pointing up, and generally, we're going to see that the beta form is going to be pointed up OH in the same direction as the carbon-6-4. So this brings to the example then the importance of the anomeric carbon. And the anomeric carbon is what we call the cyclicization carbon, where the chemistry occurred to allow for the cyclic structure.

It's the carbonyl carbon that's used in cyclic formation. And because of the fact that we differ in the OH orientation about that anomeric carbon, we call these structures in the alpha-glucopyrinose versus the beta-glucopyrinose form, we call these anomers. Important nature of the anomeric carbon, we're going to see as it relates to glycosidic bond formation.

So remember, when we talk about carbohydrates, we talked about the two classification monosaccharides, which are the simple sugars, but also to form polysaccharides. A lot of times if there's two, we'll call them disaccharides, but polysaccharides and disaccharides are multiple monosaccharides joined together. And we're going to see the critical role that anomeric carbons are going to play in facilitating the chemistry of the glycosidic bond. that allow for monosaccharides to be joined together. So we're going to stop here, and we're going to pick up in part two as we get into our polysaccharides.

Transcript for:Understanding Carbohydrates and Their Roles

Transcript for:
Understanding Carbohydrates and Their Roles