hey guys so this week we're talking carbohydrates let's get into it so carbs are our key molecule into energy production so plants make carbs i.e sugars um and we consume them to burn those sugars break those bonds get the energy out so that's really the cycle that's going on now of course you can substitute in other things it doesn't have to be glucose right it doesn't have to be that it doesn't have to be i mean it does have to be oxygen for the most part if you're going to do cellular respiration but it doesn't necessarily have to be it just usually is if you've taken microbiology you learn that oxygen is the terminal electron acceptor for many organisms it's not the only one but for the most part you're going to use oxygen you're going to burn some glucose you're going to break some bonds we're gonna get some stuff out but i have to make those bonds too so we need to talk about carbs because they're awesome great form of energy storage now that's not their only job they also serve as an important structural component and so we're gonna talk about that and let's talk about the actual name of carbohydrate so the term carbo obviously means carbon and then hydrates refers to the idea that uh if you look at the empirical formula for a carbohydrate uh sometimes you'll see a little m here too i can put it in here uh because that's not entirely true that it's that n that the number of carbons will match the end sometimes you can have extra carbons um but i left it off because i went but you have carbon and then hydrogens and oxygens okay that's your carbohydrates and so we kind of usually write the structural formula this way and that lets us uh it looks like water so hence hydrate hydration okay that's why it's called carbohydrates uh we're going to talk about all these things so we've got monosaccharides and disaccharides and oligosaccharides are not included here and then polysaccharides they're going to cover all kinds of cool things so i'm going to use a piece of a video right now that shows just some of the basics just going to get our brains thinking about carbohydrates it's really really good carbohydrates include both simple sugars which are little ring-shaped molecules made of carbon hydrogen and oxygen either alone or in pairs as well as more complex carbohydrates which are formed when these rings link up together to make long chains carbohydrates provide us with calories or energy and simple sugars in particular play a lot of roles in our diet they sweeten lemonade balance out an acidic miso soup fuel yeast in rising dough and alcohol and help preserve jams and jellies now sugars are found naturally in plants like fruits vegetables and grains as well as animal products like milk and cheese added sugars are the sugars that get added to foods like cereals ketchup energy bars and even salad dressings to be clear even if the sugar being added comes from a natural source like sugarcane or honey it's still considered an added sugar in fact a variety of ingredients listed on food labels might be sources of added sugars some of which you're probably familiar with sugar actually refers to a family of molecules called saccharides monosaccharides where mono means one so one sugar molecule disaccharides where di means two so two sugar molecules linked together oligosaccharides were oligo means a few so it's three to nine sugar molecules linked together and polysaccharides where poly means many so it's ten or more sugar molecules linked together this is from osmosis.org they make really good videos or we're going to watch the uh a portion of the rest of the video in a minute so let's start talking a little bit uh just some of the basics of our simpler carbohydrates so our monosaccharides are what we're going to start with so um but first we need to understand just the basic structures and how we're going to talk about carbohydrates okay so uh the smallest molecule that we can actually call a carbohydrate is called a triose uh and ose we're going to encounter a bunch so as a suffix so osce is a suffix that's what we call carbohydrates right so galactose fructose glucose so if it ends in ose it's a carbohydrate now carbohydrates can fall into two different categories they fall into either aldoses or ketoses and that has to do with whether or not they have an aldehyde which is their carbonyl on the end or whether they are ketones where they have their carbonyl group stuck somewhere in the middle not on one of the terminal carbons okay and so that's how we organize these now most of the carbohydrates that we're going to encounter are actually aldoses um why is that well it turns out when you have an aldehyde so when you take that carbonyl and put it on the end here it's easier to react with than if you have all these other things kind of blocking this double bond and so you can just kind of physically imagine it's easier to get something into this space here to react with this bond to form something else so like i could roll this guy attach it to the other end of this molecule which i'm going to show you in a little while um i could attach it to something else and just modify it or i could come over here and then cleave that bond and it will be easier so aldehydes in general are more reactive than ketones because they have these extra carbons on the side are sort of protecting the reactivity of this carbonyl group here okay leads into the idea that comes up a lot with um sugars and carbs and stuff is the ideas of chirality and enantiomerity or enantiomers so a little organic chemistry in here but it's not that bad so what do what does it mean to be chiral well that means uh practically it means that there are you have a carbon with four different types of groups attached to it uh and so here we have our aldehydes okay so it's one of these these are d-glyceraldehyde and here's the difference between d-glyceraldehyde and l-glyceraldehyde okay we're going to talk about that in a second and so with d we have the hydroxyl group on this side with the l we have the hydroxyl group on this side and because you have four different things you have this crazy looking thing here you have a hydrogen you have this group and a hydroxide so because there are four different things that means i can sort of have a mirror image okay so that's where our chirality well at least the chirality of our atom is concerned okay and enantiomers is what we actually call the mirror images so when we can we can flip these things over okay right if i put a line down the middle you can flip these onto each other so it's like your left hand and your right hand uh they have all the same structures but they're just in different locations and so that's enantiomers now um stereoisomers i.e if you have chirality basically all your saccharides um as long as they're aldoses can engage in stereo or mice isomeric forms so they can have chirality uh and we're going to see some examples in just a second and that can actually have a big effect on what they're used for glucose is probably the simplest one to actually look at so here's glucose here it's got six carbons c6h12o6 awesome uh but how we can figure it because we have chiral atoms okay we have chiral carbons uh we have multiple chirocarbons we are able to uh maintain the location of the r groups or whatever is attached to those carbons okay and so uh you can maintain those and then as they're folded over or reactions happen then they're going to maintain their location even though the content is the same and so natural glucose looks like this is the deconformation so you have three on the right and one on the left that's kind of how i view it now when you artificially generate glucose okay it's l-glucose and all over on the left see that but we don't really care what the key one here is we're looking at this chiral carbon here okay because you can flip them it doesn't really matter this one is the chiral carbon that decides whether it's l or d because that's that's what determines if it's glucose or not i'm going to show you some later on if i start flipping some of these hydroxyls we actually change the name okay but you can see this isn't my favorite thing because it gets really complicated and some of the terms get really complicated and so i apologize uh but honestly it's not too crazy it's just wherever you put that hydroxyl group lets you change the name it's not that complicated so let's keep going let me just talk a little bit i've been showing you fisher projections so that's when you linearize uh the carbons that sort of carbon backbone that the sugars are going to be made of okay and if you fold those carbons over on themselves okay so if we actually uh form the bond here between basically this oxygen is going to go attached to this carbon here okay and so if you imagine that you're sort of like on a plane here so a p-l-a-n-e so all the carbons here so there's one two three four five six carbons uh these five carbons here are sitting existing on a plane okay and then off of that plane your hydroxyl groups are either gonna stick up or they're going to stick up this is actually supposed to be sticking out so they'll stick up the blue one's sticking up and then these red ones are sticking down so let me show you a better better picture here so uh we've got our carbons here so there's our fisher projection okay and they're colored okay so there's the red one the green one the pink one the blue one other blue one and there's the oxygen okay they actually form to this carbon here okay and uh off of that we can see where so there's my plane of existence right so this is in three dimensions and so one of the hydrophones is sticking up this one's sticking down this one's sticking up this one's sticking down okay up down up down and if i change how those are arranged it can actually change um the functionality it can change how reactive it is it can change the actual name that we give them which is kind of fun okay so let's keep going there's lots of different monosaccharides it just kind of depends on how many carbons you're going to include so you have your aldoses and ketosis so that's your three carbonars carbons i just made that up that's your three carbon molecules um and then as you add carbons that so glyceraldehyde is an aldose okay it's got an aldehyde on the end notice all of these are aldoses okay and then you can also have ketones which is dihydroxyacetone is a ketone now all the rest of these are aldoses and so the number of carbons decides what number gets up front so if i have three carbons it's trios if i have five carbons it's pentose if you have six carbons it's hexose now most of the uh if you're not doing anything weird uh then most of the time you're going to be encountering pentoses and mostly hexoses but hey sometimes if you're doing weird stuff maybe you'll have a quadros or whatever tetros it doesn't even list them because that's like super rare unless you're doing weird chemistries but we're going to assume that you're not doing weird chemistries now of course these are fissure projections so we can look at um what do you call these hayworth projections sorry i forgot uh so you can look at the halos projections and so you can just see structurally what's going on and i always center myself on the oxygen so uh here's my typical glucose molecule looking right there okay now monosaccharides basically are these three are the monosaccharides that we're going to be dealing with most of the time okay you can have other monosaccharides okay so like riboses and deoxyriboses those are pentoses right they only have five carbons so we've got one two three four five carbons one two three four five carbons right that's what we use to make our nucleotides when we're actually making our carbohydrates like for energy then we rely on more on our uh haxos's which have six carbons so one two three four five and then you get that six one sticking off there now for fructose which is uh one of the monosaccharides one of the three it's a little different it kind of looks like the pentoses but notice you got this extra carbon hanging off the bottom here so sometimes people like well those look the same well they're not actually the same it's just the carbons i mentioned uh just a minute ago that where we put those hydroxyls right where the uh whether on the top or the bottom and i can change where these are on the actual molecule um this uh refers to we can use those to keep track of the actual types of aldoses that we have okay and so you can see the d series so these are naturally formed um aldoses okay so aldos is just they have there are aldehydes this is most of the sugars that we're gonna encounter so you can see down here on the bottom we've got our glucose and we've got our mannose and we've got our galactose okay those are three biggies okay and so we've got our we have three on the right one on the left two on the left two on the right galactose two on the left two on the right and so you can just kind of see basically we just change the names based on where these things go uh arabinoses uh show up uh riboses there's your ribose xylose you'll see sometimes but there's a bunch of these that just never show up like goulos i don't know it's just really weird idose um they're just generally don't get made you can synthesize them but for the most part but hypothetically they can exist and so yeah that's what that is one question gets brought up all the time who cares okay well it actually matters because for example if i'm going to build like a polymer of sugars okay so now we're not talking about polymers yet but i just want to bring it up because it has to do with where your hydroxyls are so in alpha glucose so just to orient yourself there's the oxygen right so we're looking at this first carbon here and this first carbon is going to decide r uh that it's a glucose oh sorry that the this hydroxyl is down so it's a glucose and then we get to flip this one sorry so the number two carbon decides if it's the glucose the number one carbon gets to decide if it's alpha or beta okay and so we're gonna look here and we're gonna flip our hydroxyl down that's an alpha okay and if i link a bunch of those together with uh glycosidic linkages which we're about to talk about then i get this kind of formation of all these alphas this is a typical formation for starch which is a very digestible yet long-term storage molecule okay so this would be your starches so like things that you can eat like um i don't know like uh complex carbohydrates when you hear complex carbohydrates this is what they're referring to there's these long chains of sugars um they're not monomers they're polymers um and so that's what they form but it's digestible now the key there is if i jump over here okay i've got all these uh beta glucoses so that's where the hydroxyl group is pointing up here okay and i'm going to kind of keep flipping them so if i keep attaching all these betas to each other you can see they start getting like kind of this weird shape so in order to get them to actually bond together properly i have to flip them so half of them are flipped and so you see the little blue the little yellow blue fan the little yellow hydroxyl groups that determine whether this is a glucose not pointing down up up down up down up uh in comparison to each other as these are all down derp i'm just saying what's really obvious um if they're like that that is cellulose so that is an indigestible fiber right so if you feel like oh i gotta eat uh wheaties because i need fiber or whatever i don't know um you gotta eat your leafy greens to get cellulose in your uh colon to help clear out your colon that's what this is so this is indigestible so that that one simple change okay so having that hydroxyl group either point down or point up can decide whether or not an enzyme is able to break it or not okay really interesting so that leads us into these types of linkages which these types of linkages let us i saccharides so that's where we're going to take two monosaccharides okay whatever they are and stick them together using a glycosidic bond or a glycosidic linkage it's just a dehydration reaction okay or yeah infused so there's condensation reactions and there's dehydration reactions so dehydration reaction is the loss of water if during a condensation reaction whereas a condensation reaction isn't necessarily a loss of water it's just the loss of a small molecule when you're combining two things so dehydrations are condensations but not all condensation reactions are dehydrations whatever you're forming a glycosidic linkage here between these two now i wanted to go back to that original video that we were watching and they're going to talk about the different disaccharides that exist and the kind of foods that they're in glucose is the most important member of the sugar family and it's a monosaccharide it's one of the main sources of calories for the body and is able to cross the blood-brain barrier and nourish the brain another monosaccharide is fructose which is commonly found in honey fruits and vegetables finally there's the monosaccharide galactose known as milk sugar it's known as milk sugar because it's only found in nature when it links with glucose to form lactose a disaccharide found in the milk of mammals which includes cow milk as well as human breast milk sucrose or table sugar is another disaccharide and it's formed when fructose links up with glucose sucrose is found in various fruits and vegetables with sugar cane and sugar beets having the highest quantities maltose is another disaccharide and this one has two glucose molecules linked together and it's found in molasses which can be used as a substrate to ferment beer sugars like fructose for example are most always found in combination with other sugars and the combinations can be pretty different even in seemingly similar foods for example in honey fifty percent of the sugar is fructose forty four percent is glucose four percent is galactose and two percent is maltose worse in maple syrup less than one percent of the sugar is fructose three percent is glucose and 96 percent is sucrose so simple sugars whether they're natural or added are mixtures of monosaccharides or disaccharides next there are the complex carbohydrates there are oligosaccharides like galactooligosaccharides which are short chains of galactose molecules like those found in soybeans then there are polysaccharides which are even larger chains with branches and are the most abundant type of carbohydrates found in food starches are polysaccharides with molecular bonds between sugar molecules that human intestinal enzymes can break down starches are an important source of calories and can be found in foods like rice potatoes wheat and maize starches don't taste sweet like simple sugars because they don't activate the taste buds in the same way and there are also dietary fibers which are carbohydrates that intestinal enzymes can't break down and so the body can't digest them so just to make sure that uh in case you're not watching the video in case you're just looking at the slides i just want to include this on here the big ones uh lactose you encounter in milk all the time sucrose is just your basic table sugar and then maltose we don't encounter like just purely that often it's usually more of a mixture but molasses is the big one that you encounter that in and if you're making beer that's uh you you germinate the um i lived in colorado where they make a lot of beer so you get your malt and you germinate it in water and then you get maltose out of it out of the endospore i guess anyway doesn't really matter it's just the different combinations of your various monosaccharides and that's how you get your disaccharides awesome now let's move on to a little more complicated we're going to start tacking on more and more sugars and as we start tacking on more and more sugars we call those oligosaccharides so basically anything under 10 would be considered a lego saccharide though i i sure you could find examples of oligosaccharides that exceed 9 sugars but for the most part most of our oligosaccharides stay under that boundary okay so if it's three right because it's a disaccharide so we're uh the disaccharide is two so we're gonna move on to trisaccharides and beyond um and that's basically uh it's not really for energy consumption though you could break these sugars off and use them for energy they're more for signaling so tons of signaling molecules are oligosaccharides by themselves or attached to proteins and so just by themselves they can be signaling molecules so here's just a bunch of examples in human milk um prebiotics which is something basically a prebiotic is what bacteria can consume uh that are probiotics that then like make your health better so you can eat probiotics to make the probiotics work better uh it's a whole subfield that's mildly under my phd but i don't know we don't have to talk about that but anyway prebiotics are interesting uh you should eat healthy food is what this really means don't eat gross stuff because they're all artificial and all the sugars are artificial you can see the variety so uh i like these charts because they just if you get super into this stuff then you can just see like oh this one's got a few ghosts on the end oh wow that's very interesting and a galactose wow that's very very exciting anyway you can see it gets kind of complicated as you dig deeper uh some people are super into like a sacrifice some people are not it doesn't really matter but they do have a wide variety of associated functions okay so from vitamin b to uh blood pressure changes uh to the absorption of calcium and menopausal women like it's crazy um i clearly got this chart from an older paper because these are all from like when i was in high school but just to give you some idea of the variety of functions that these really big oligosaccharides can have now jumping off of that they don't have to just exist by themselves we can take oligosaccharides and attach them to proteins specific protein residues and we can then have them serve a function so they could act as a cell surface receptor for something or they can be a cell surface marker to mark a cell for whatever there's so much variety that you can actually engender in these that it gets incredibly complicated really really really really really fast okay now there are two types we call these glycans so that's glycoproteins when we glycosylate okay so glyco meaning like sugar insulation basically meaning we are attaching so that's when we're attaching sugars to either lipids or proteins okay and i'll show you some examples of lipids too uh but for in this case we've got like asparagine down here right which is our um an amino acid and so we're going to take some sugars and attach those so we're going to take our oligosaccharide our multi sugar chain and we're going to attach it to either an asparagine okay uh so that's called an n-glycan okay or we have o-glycans which that's where you attach it either to a serine or a threonine okay um this is me being crazy crazy common on cell surface proteins yes you can have immune disorders uh where you are not properly either putting these on or uh they're you're putting the wrong ones on the cell and that can cause an immune disorder because we use these to recognize cells for their functionality like oh is that a type of cell or not well that's a good question let's look at it let's look at their proteins and see if they have the correct oligosaccharides um and so it's really interesting so they're added on in the uh rough endoplasmic reticulum because it's a protein right that's you that's going to be put on the surface of a cell so it has to go through the rough er and that's where you get your initial addition and then it's going to go to the golgi to have extra polysaccharides added or extra sacrifice sorry so there's a video that i want to show you i apologize for the quality it's like the best version of this video i can find and it drives me crazy because i'm like oh my gosh this video is super good the quality is like really bad but the content is so good so we're gonna cut to that it's going to show you this process actually glycosylation adding sugars to proteins begins in the endoplasmic reticulum and continues in the golgi apparatus let's examine the process for one protein enzymes in the er remove glucose and mannose residues from the oligosaccharide chains vesicles transport the glycoprotein to the cis golgi network where one of two events occurs either n acetyl glucosamines attach to the oligosaccharide and are transported to the lysosomes or enzymes remove more mannose residues vesicles transport the modified glycoprotein to the medial golgi cisternae where glucosamine attaches and more mannose molecules leave the molecule vesicles now transport the glycoprotein to the trans golgi sister knee there galactose and cyalic acid join the chain the glycoprotein is finally ready for transport interesting stuff right i apologize for the quality again uh but there that these videos from uh they're really well done from uh some of the textbook companies and then they just like never put the actual videos out so you have to like find people who have like the cd from like the cd-rom from like 20 years ago that had the videos on it anyway um so i also want to show you one other video i'm only going to show you the first part um it's more to emphasize how complicated some of these can actually get and that there is an entire sub industry of biotechnology devoted to the addition or the analysis of these sugars on proteins and so this is going to come from a pharmaceutical company that sells reagents to actually do this kind of work secretory and membrane proteins are often post-translationally modified with sugar chains called glycans glycans are essential for the stability and function of the mature protein they affect enzymatic activity half-life and receptor binding among other biological processes proteins can be modified with different kinds of carbohydrates n-glycans and o-glycans being the most common types in eukaryotic systems n-glycans are attached to asparagine residues of the protein shown with an n n-glycans have a common biosynthesis pathway which is reflected in the common structure of their core n-glycans can be high mannose which means all the component monosaccharides are manos residues with the exception of the two core n-acetylglucosamine or glycnack residues n-glycans can also be complex which means the mannose residues are only present at the core and the branches are extended with other monosaccharides such as n-acetylglucosamine or glyc galactose cyalic acid and fucose o glycans start with the addition of an n acetyl galactosamine or galmac residue to a serine shown with an s or threonine shown with a t o glycans are often short chains consisting of only a few sugars or they can be extended by the addition of different monosaccharides resulting in a longer chain d-glycosylation refers to the removal of glycans from proteins enzymatic glycosylation is the method of choice because it preserves the integrity of the protein and sometimes the glycan chains for further analysis uh much higher quality video from new england biolabs or nab as we usually call it if you're a nerd and they basically sell the reagents and the equipment to analyze the oligosaccharides on the surfaces of cells and those are just ways that you can study a cell and see what it's trying to do so where else do we see oligosaccharides so um here is an immune example so up here we have p-selekin and psgl1 so it turns out that immune cells like to travel along your blood vessels so this is the blood vessel there's blood vessel wall there's your endothelial cells and your immune cells so you get some neutrophils and some macrophages or monocytes when they're flowing in the blood but they're macrophages and there's a t helper cell and all these guys will uh express psgl one based on the actual presence of cytokines that are floating in the blood okay and so if they're expressing that they kind of reach out with little grabby arms and are looking for this molecule so the leukocyte or the neutrophil t cell whatever it is is reaching out with this psg01 which is covered with all these sugars and those sugars need to match up with p selected which p selection is expressed on the endothelium and so you can imagine uh let's say down below where my cursor is down here so down here i actually have a um like somewhere there's damage so maybe there's an invader i've got a cut going on and so you can see i filled the cut in with platelets here but i'm going to express p selecting nearby to reach out and grab the little arms of the psgl ones from the immune cells and so they only recognize those because they are glycosylated properly which is really really interesting and bring it back to immunology so uh glycosylation isn't relegated just to proteins though you can also glycosylate lipids we call those glycolipids okay if i take a lipid and i attach some kind of sugar to it okay those are glycolipids there's a huge variety of these just like there are glycoproteins um just having them on the cell surface can signal things but oftentimes you can also put them into the cell membrane uh it can either add to stability it can be tracked from membrane stability uh it just kind of depends on what you're trying to do um and it has more to do with the this end of the structures where we're actually adding um this is the only glycolipid on here is this one it's just to contrast it with these other guys but you could put it on the on the surface here and that could signal to another cell because this is what would be facing out right and this would be facing in towards the actual fossil of the bilayer and so you can attach different sugars here it acts as a signaling molecule now you could embed a protein and put sugars on it too like that's what we're doing here but this is different so you can just attach it right onto the lipid which is kind of fun now another common example um blood type gets brought up all the time but we need to talk about it because blood typing actually is based on glycoproteins and glycosylation of proteins and so if you're oh like me this is what the structure looks like and i apologize for the quality it's because it's like a 2007 picture but so this is the actual structure so you've got your galactose you've got your n acetyl glucosamine which is uh basically a glucose derivative with uh a nitrogen attached sorry uh and then you've got your galactose and then you've got your fucos okay and so you can see that that same structure is in the a antigen as well as the b antigen okay and so that is maintained okay and so the only real difference between a antigens is that i attack on another an acetylglucosamine or i'm sorry an n acetyl galactosamine oh man or i replace that with a galactose and you can actually express both of these okay so if you are a b that means your cells are codominant they are expressing both of these so you would have if you looked at one of your red blood cells it would have an a antigen sticking on there and you could look at other ones and they would have a b antigen on there and that's the only difference is this little square and this little circle okay but they all have the o possibility okay so that's why o is the universal donor because it can go into any of these cells and they won't attack o as being foreign because they all contain the o antigen so the o is just kind of like subtly hiding underneath the a antigen and the b antigen so this is why you can't take an a antigen and put it into an o patient okay a blood and o blood don't mix um but an a patient can take o blood okay and so that's where that comes from hey i brought it back to the immune system again now let's get to some of the fun stuff let's talk some polysaccharides so if you have 10 or more obviously that's a caveat so it's basically more 10 or more repeating units um so that's contrasted with i mean obviously some of uh some of these structures can have more than nine uh but for the most part what we're saying is okay we have this continuous repeating unit that's your polysaccharide so yes they are polymers um but yeah they're polysaccharides and so there's lots of different examples um cellulose being like the indigestible component of plants it's your fiber when you eat fiber and then there's lots of other things so different kinds of starches that you can eat um and glycogen is what we use to store energy inside of our livers okay we take glucose and we convert it into glycogen and that's just a longer term storage molecule you're basically it's more efficient because you can cram more of it into a smaller space and it's it's it lasts longer it doesn't get digested as rapidly and so you can store it lower anyway branching is important so how branched it is controls uh sort of how accessible it is um which is interesting and uh the actual structure of cellulose is really really interesting uh and so how they are organized how we actually form those glycosidic bonds is really really important okay so there we have our our beta glucoses where we're flipping them okay and then the starches of the alphas glycogen and starch notice are really not that different um and then chitin okay is where you're using an acetyl glucosamine and almost the exact same structure as cellulose so you see you get that structure structurality that's not the right word the uh the power of the structure because you have this bond all going up and down so you get the i don't know the structural power of it uh but it's just a different sugar molecule because we took an n and stuck an n on there instead of a hydroxyl group uh but it's still the structure is very very very similar all right so that's polymers other polymers so uh if you've taken a microbiology class you may know that peptidoglycan is a really important component of basically all bacterial cell walls um and so you can see it here in the brown and green alternating so that's the the glycan portion uh the peptido portion is the little amino acids that are connecting them together here okay so gram positive bacteria have a huge massive thick chunk of peptidoglycan gram negatives have a nice thin layer mycobacteria also do have peptidoglycan um it's not as easy to kill them though because they have this giant massive set of glycolipids hey look at that so we've got our lipid portion and then we're going to stick on a oh i guess this is the limited portion then you've got the little glucose or whatever it is i don't actually know which is a glycolic acid but anyway so you can see you're able to glycosylate and that's really really important for structure and over here on funguses which also have chitin as a structural component there's other things too so they've got proteins with a bunch of mannoses on them you've got beta glucans so you can see it's not just for energy storage but for structure as well a couple things i wanted to talk about i want to give you some actual examples so um because let's be honest i struggle with keeping carbs interesting i mean i've tried to give you some examples where like signaling molecules or whatever like you can dig really deep um but a couple examples that come out of things that i'm interested in so vaccines i've always been interested in and so uh there's actually a polysaccharide vaccine that we have uh there's actually two types of them and they're for strep pneumonia so the trick with strep pneumonia which causes like so many diseases it's really bad so it's streptococcus right so it's a string a little string of cocci little circles and they have a really powerful capsule powerful meaning it's like a really strong virulence factor so uh that capsule of all these mucusy sugary looking things uh prevents uh immune cells from attacking it and so uh here is the there's the bacteria itself right so it's a circle and it's a little sphered and uh because it's caucus and then it's got all these crazy there's so wall and then it's got all this extra capsular material and tons and tons of different polysaccharides there are 91 different types of polysaccharides just in the strep pneumonia capsule that's crazy there's so much going on okay and so uh it causes a ton of human disease like it's really really bad it kills people it hurts people a lot and so uh what they try to do was they said okay it's the actual proteins on the surface of the bacteria are hiding underneath the capsule so can we make a vaccine against the capsule well that's a good question it's it gets a little tricky so the trick with making a vaccines that work against polysaccharide antigens is that sugar antigens okay so an antigen is any foreign molecule right and so you can imagine we've seen lots of examples of sugars um the actual like oh yeah to have a mannose with a galactose and an n glucosamine or whatever the actual structure of sugars is not as different between creatures and so it can be kind of tricky to actually uh make um an antibody response against a polysaccharide but you can do it uh but the problem is most of the antigens that we deal with as creatures as humans as eukaryotes that have advanced immune systems like this mammals i should say most of the antigens that we deal with are proteins and so most of the recognition machinery so your mhcs are designed to look for protein antigens and so in order you can make antibodies against sugars it's just more difficult to actually get the body to do it and so that's why we conjugate them so we take a pneumococcal conjugate vaccine so that's the pcv13 this is one you want to get you can get the pneumococcal um it's the non-conjugate it's just the polysaccharide vaccine that's this one this will only give you passive immunity so you kind of make some antibodies but it's not great and so what they did was uh because the polysaccharides themselves from this capsule are not super immunogenic they are different enough so we can attack them without attacking the body but it's really hard to get an immune response so what they did was they took the diphtheria toxin okay and it's a protein it's the toxin that gets secreted by diphtheria um and which is bacteria and it secretes the toxin and it can hurt you really bad and so we take a little portion of that we take the toxin portion off obviously and then attach that to the actual polysaccharide and so that's kind of what's going on here so um here is the diphtheria toxin okay that's the diphtheria toxin so we took off um the uh receptor binding domain okay so where is it uh hang on it's just a a sub component of the actual diphtheria toxin which has two components the a portion is the one that will actually kill you they disable ribosomes which we haven't really talked about that much but they stop ribosomes from being able to make proteins so hence why diphtheria toxin can kill you but we just take a little piece of that it's super immunogenic and so when you take just this little protein portion and stick it onto anything that other thing that you attach it to so it could be a polysaccharide or anything else um can become really immunogenic and you can make antibiotics against it and so that's what this conjugate vaccine is so that's what the conjugation actually is the where you're conjugating it and so that's what this part is so you can have just a polysaccharide vaccine by itself but it doesn't work super great but when you actually do that you get really good b-cell response which is awesome now the last thing i want to show you is a video and that's just going to end this video is a video of hiv okay because that was my field for like 10 years and hiv has a bunch of glycoproteins and so i wanted to show you a really good well-animated video of the glycoproteins and how hiv uses its glycoproteins that it stole from a host cell somewhere else to actually invade another host hiv-1 attachment inhibitor proposed mechanism of action infection of a host cell by hiv leads to formation of new viral particles death of the infected cells and ultimately destruction of the host immune system hiv particles carry gp120 proteins on their outer envelope which play a vital role in allowing the virus to bind to host cd4 positive t cells attachment to the host cell represents the first step in viral entry and infection of the cell this initial interaction between the virus and the cell mediated by the viral gp120 protein represents a novel target for antiretroviral drug development hiv first binds to the cellular cd4 receptor present on the surface of the host cell cd4 binding is mediated by the hiv gp120 surface glycoprotein which together with the transmembrane glycoprotein gp41 forms gp160 which is present as a trimer complex on the viral envelope in order to enable cd4 binding gp120 must undergo a series of internal structural rearrangements this process begins with rearrangement of the so-called inner and outer domains of hiv gp120 gp120 then undergoes further internal rearrangements in the region surrounding the cd4 binding site which enable it to adopt a cd4 binding competent state once in the cd4 binding competent state gp 120 can bind to the cd4 cell following binding to cd4 gp120 undergoes further folding which leads to exposure of its co-receptor binding site exposure of the gp120 co-receptor binding site enables engagement of the chemokine ccr5 or cxcr4 co-receptors following co-receptor binding additional structural alterations expose gp41 which inserts into the host cell membrane this initiates a series of major structural changes in gp41 that bring the viral and host cell membranes together resulting in membrane fusion and release of the viral core into the host cell cytoplasm this is where viral replication starts the conformational changes that gp120 undergoes are critical in order for the virus to bind to and enter the cd4 cell attachment inhibitors represent a novel class of antiretroviral drug they prevent the initial interaction between the virus and host cell blocking subsequent viral entry into the cell the attachment inhibitor binds to the outer domain of hiv-1 gp120 on the viral envelope just underneath the region for cd4 binding once the attachment inhibitor is bound to gp120 the region surrounding the cd4 binding site can no longer rearrange into a cd4 binding competent state as gp120 is not able to bind to the cd4 cell subsequent viral entry is blocked in summary attachment inhibitors prevent the first step of viral cell entry attachment to the cd4 cell membrane this is in contrast to current entry inhibitors which act after initial binding of the virus to cd4 you