Lecture 14. Glycobiology.

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Lecture 14. Glycobiology.
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Lec 14. Introduction to Chemical Biology -- Glycobiology
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UCI Chem 128 Introduction to Chemical Biology (Winter 2013) Instructor: Gregory Weiss, Ph.D. Description: Introduction to the basic principles of chemical biology: structures and reactivity; chemical mechanisms of enzyme catalysis; chemistry of signaling, biosynthesis, and metabolic pathways. Index of Topics: 0:02:04 Enzyme Functions 0:06:10 Serine Based Proteases 0:10:44 Protein Based Inhibition of Proteases 0:13:10 Covalent or Mechanism-Based Protease Inhibitors 0:15:02 Inhibition of Serine Esterases 0:17:07 Enzymes Use Co-Factors (Vitamins) 0:21:31 The Origins of Stereospecificity in Alcohol Dehydrogenase 0:24:09 Pyridozal Phosphate (Vitamin 86) 0:27:29 PLP - Catalyzed Transamination 0:29:29 Protein Engineering 0:36:16 Most Mutations Make the Protein Less Functional 0:38:17 Carbohydrates 0:44:30 Hemiacetal Reactivity and Formation 0:46:33 Glucopyranose is the Most Noteable Ring Configuration 0:47:51 Oligosaccharides of the TB Coat 0:51:29 Oxocarbenium Ions as a Key Intermediate in Hydrolysis of Glycosidic Bonds 0:53:19 Mechanisms of Enzymatic Hydrolysis 0:54:58 Commonalitites in Glycosylhydrolase Mechanisms 0:56:03 Neuraminidase: Key Enzyme in Influenza Release from Surface to Cell 1:01:06 Oligosaccharides 1:04:22 Polysaccharides 1:08:04 Hyaluronan: Oligosaccharides in Joints 1:09:57 Glycosylated Proteins
Übergangszustand Surface science Carbohydrate Carbon (fiber) Topicity Chemistry Reactivity (chemistry) Chemische Biologie Gesundheitsstörung Enzyme Sweetness Protein Chemical structure Storage tank Stuffing
Übergangszustand Growth medium Steel Binding energy Phosphorous acid Hydro Tasmania Chemistry Enzyme Machinability Electron Protein Enzyme inhibitor Whitewater Walking Topicity Addition reaction Chemical reaction Electronic cigarette Systemic therapy Acid Medical history Stuffing Ester Sunscreen Wursthülle Reactivity (chemistry) Magnesium Meat analogue Amino acid Isotretinoin Active site Explosion Tool steel Cell biology Supercooling Side chain Process (computing) Histidine Metal Area Molecularity Stickstoffatom Hydrogen bond Molekulardynamik Carbon (fiber) Protonation CHARGE syndrome Water Joint (geology) Bone marrow PH indicator Functional group Covalent bond Chemical structure Vitamin Base (chemistry) Carboxylierung
Activity (UML) Peptide Sunscreen Wursthülle Radioactive decay Methylgruppe Chemistry Hydrolase Enzyme Protein Controller (control theory) Amino acid Active site Faserplatte Pain Beer Setzen <Verfahrenstechnik> Substituent Metal Molecularity Enzyme inhibitor Topicity Chloral Abundance of the chemical elements Chemical reaction Erdrutsch Electronic cigarette Heck-Reaktion Functional group Covalent bond Chemical compound Medroxyprogesterone Tablet (pharmacy) Brown adipose tissue Vitamin Stuffing
Antigen Sense District Malt Nicotinamide adenine dinucleotide Electrical breakdown Chemical plant Molecule Origin of replication Ethanol Enzyme Active site Library (computing) Transformation <Genetik> Aluminium hydride Periodate River mouth Area Alkoholfreies Getränk Hydride Reaktionsgleichung Walking Chemical reaction River source Alcohol Erdrutsch Electronic cigarette Wine tasting descriptors Fat Water Hydrogen Sodium Acid Stream gauge Branntwein Functional group Vitamin Medical history Deuterium Stuffing
Übergangszustand Sunscreen Hydroxyl Wursthülle Radioactive decay Chemistry Reactivity (chemistry) Alpha particle Glutamic acid Enzyme Electron Tidal race Amine Amino acid Faserplatte Elektronentransfer Area Metal Stickstoffatom Octane rating Singulettzustand Asset Carbon (fiber) Protonation Chemical reaction Man page Electronic cigarette Acid Tyrosin Phosphate Covalent bond Chemical structure Pharmaceutical drug Carboxylierung Vitamin Base (chemistry) Sauce Thermoforming Stuffing
Alkoholfreies Getränk Setzen <Verfahrenstechnik> Potenz <Homöopathie> Proteindesign Chemical property DNS-Synthese Hydroxyl Adamantane Wursthülle Mutagenese Genotype Gesundheitsstörung Functional group Materials science Polymorphism (biology) Protein Urea Amino acid Cobaltoxide Side chain
Residue (chemistry) Carbohydrate Proteindesign Binding energy Nuclear receptor Hydro Tasmania Wursthülle Organische Verbindungen Reactivity (chemistry) Anomalie <Medizin> Sample (material) Enzyme Polymorphism (biology) Tachyphylaxie Protein Phenylalanine Amino acid Growth hormone Side chain Hydrophobic effect Chemical formula Chemical property Carbon (fiber) Topicity Maskierung <Chemie> Chemical reaction Mutagenese Genotype Emission spectrum Water Drop (liquid) Functional group Base (chemistry) Alanine ISO-Komplex-Heilweise Satellite DNA Stuffing
Sense District Carbohydrate Chemical plant Wursthülle Block (periodic table) Chemistry Alpha particle Reactivity (chemistry) Molecule Shear strength Cell (biology) Beta sheet Periodate Side chain Alkoholfreies Getränk Octane rating Chemical property Carbon (fiber) Adamantane Chemical reaction Erdrutsch Wine tasting descriptors Water Chemische Biologie Functional group Pharmaceutical drug Chemical structure Cobaltoxide ISO-Komplex-Heilweise Stuffing
Chain (unit) Fruchtsaft Carbohydrate Gene Wursthülle Reactivity (chemistry) Ring strain Tidal race Electron Protein Data conversion Explosion Entropy Chemical reactor Area Surface science Reaktionsgleichung Octane rating Tuberculosis Malerfarbe Topicity Carbon (fiber) Protonation Hydroxide Food additive Branch (computer science) Systemic therapy Gesundheitsstörung Acid Tiermodell Functional group Covalent bond Base (chemistry) Cobaltoxide Stuffing Isotropy
Sense District Carbohydrate Organische Verbindungen Wursthülle Chemistry Neuraminidase Distortion Enzyme Cell (biology) Hydrolysat Common land Sea level Periodate Cell membrane Conformational isomerism Setzen <Verfahrenstechnik> Pond Surface science Enzyme inhibitor Glykolsäure Octane rating Tuberculosis Carbon (fiber) Chemical reaction Multiprotein complex Solution Alcohol Electronic cigarette Hydroxide Glykoside Chemische Biologie Sodium Acid Gesundheitsstörung Functional group Covalent bond Substrat <Chemie> Medical history Cobaltoxide Thermoforming Host (biology)
Glucose Übergangszustand Chain (unit) Proline Carbohydrate Binding energy Hydro Tasmania Atomic orbital Enzyme Polymorphism (biology) Ballistic trauma Periodate Cell membrane Gas Chemical reaction Hydroxide Acid Attachment theory Phosphate Azo coupling Chemical compound Wasserbeständigkeit Stuffing Ethylgruppe Recreational drug use Activity (UML) Atomic orbital Hydroxyl Wursthülle Zanamivir Ästuar Neuraminidase Diet food Lead Cell (biology) Oxalsäure Active site Jukos Coast Province Asset Carbon (fiber) Hybridisierung <Chemie> Slate Ice Ingredient Metabolic pathway Functional group Covalent bond Substrat <Chemie> Carboxylierung Base (chemistry) Satellite DNA
Carbohydrate Polysaccharide Hydroxyl Gene Wursthülle Lightning Alpha particle Diet food Meat analogue Starch Cellulose Potato chip Sweetness Cell (biology) Beta sheet Active site Butcher Solubility Beer Surface science Stickstoffatom Precursor (chemistry) Walking Extruderwerkzeug River source Multiprotein complex Abundance of the chemical elements Erdrutsch Joint (geology) Water Acid Stream gauge Functional group Covalent bond Chemical structure Polymer Base (chemistry) Separator (milk) Carboxylierung Helicität <Chemie> Thermoforming Stuffing
welcome back can offense today would be talking about proteins and then we're going to go into much sweeter topics as the transition to quite a biology so I've got some really cool stuff in store for you today and I can't wait to get to it I'm specifically were going to be talking about Guangqian structure these are the carbohydrates found on the surface of the of yourselves but things that make life the suite will be talking about their reactivity and how enzymes can hide your lives there and then will talk about what it is that they're doing before we talk about why there are ultimately going to kill us so why is it that carbohydrates sugars taste so sweet yet cause so much disease is something that fascinates me I'd love to understand that better and let's get started and hopefully we will all candidates little picture I have a picture of the great Hermann Emil Fisher laboratory around 1900 disguises superhero of chemistry and he was doing things like working out structures of carbohydrates just years after people have figured out that the carbohydrates actually that carbons actually had Cereal Chemistry so this guy is a tour de force canister trying to giant in the field of Geico biology and chemical biology and he's 1 of my heroes OK some quick
announcements I'd like you to read Chapter 7 work .period problems and and then you're going to be receiving back your journal article reports sometimes you today or maybe in discussion section the operated out of 75 points I and went something like a bell curve but I'll be honest they were really good I got some fantastic journal article reports that they were tough degrade it was hard to come up with a standard distribution I like to see them so Nice job on this book report on this journal article reports that you ought to be commended excellent job are at odds over here so we saw last week last week I was telling you about how it is that proteins function what it is that makes them so great when they do the things they do and what we saw was that of enzymes work by lowering the transition state energy for reaction doing this really take a transition energy it's up year and push it down here as the need of of accelerating the reaction speeding it up pressing the go pedal to the floor this is really cool this is powerful this makes biology possible so because these enzymes evolved to bind to transition states analogs of these transition states are very effective as inhibitors of the enzyme the stick in there and they plug it up like a hole that might above In a door something like that they're very effective at shutting down the enzymatic reactions and the fact we're going to see a few more examples of that today 1 indication we saw last week how enzymes take advantage of their diverse functionality of the amino acid side chains showed you for example examples of metal ions magnesium providing Louis acidity in the case of kind basis we talked about how license I'm has the Bronstein acid and said based functionalities and the 2 of them were like a one-two punch where the acid was up here and then the base down here and then they switch places this is truly remarkable chemistry in action and it's 1 of those power tools in biology the next thing we saw is that our services will receive today Is that additional functionality from vitamins Coke factors can expands the range of chemistry so we start with the easy stuff the brands as the Brunson bases but just you wait I've got more functionality for you and this other functionality is super cool because it allows a whole new range of reactivity and access to some reactions that otherwise would not be possible in water and then finally on the major theme really all of our last lecture is this concept of dynamics and this is 1 of the challenges that has tormented me really for years I have always we always is too strong a word I wanted to for the last 10 years understand why it is that enzymes flap around the way they do and handset flapping in their catalysis and when I showed you were there the sort of cutting-edge theories about how is that these things work and I showed you examples where that flapping is both beneficial and deleterious for enzyme function right we saw an example where where the enzyme protein tiny say was was munching away in a neat waltz and even called it a waltz right because at 3 steps 1 2 3 just like a waltz and then sometimes they got stuck on Sept 1 2 and was doing almost like a room but it was going backwards and forwards 1 2 1 2 and not going into the wall so it should be and that's a disaster for the self because when that happens Florida disaster for demands when that happens the enzyme is not going all the way to make its product it's getting stuck and that's darkness is inherent to the function of a protein kind is like protein kindness said this is a protein that evolved not necessarily to be a monster catalysis it evolved to be a highly regulated bowl molecular switch reconstruction on any could switch at all and that ability to get stuck doing 1 2 1 2 where should be doing 1 2 3 1 2 3 is useful but that's the kind of ability that allows the protein kind to be a useful tool in in cell biology OK so I'm hopefully you're getting some idea of how enzymes work I went to pick up on a topic I can't stand over but it's super and I feel I felt guilty frankly for skimming over this this is just too cool and too interesting so let's go back and take a quick look I would start by talking about a class of enzymes called Syrian-based courteous This is a class of enzymes like this is steel producers that we saw last time that relies on having a serious functionality in its active site and that series functionality has an analogous role to the Sistine an active site of the Sistine in both cases the Serie in high over the Sistine in both cases those functionalities actors a nucleophile to attack the I am bid bond that's going to be high joints and so let's take a quick look at best and in the active site of a series producers there is a catalytic triad consisting of the series functionality together with the history and together phosphoric acid and these have the remarkable ability to act as a protein relay system where the protein gets handed off from 1 functionality to the other and by doing that that actually allows the series to be a much better nucleophile so check this out in this case what we're saying is that this series is getting deeper donated by the men nitrogen of his emitters all of history and in turn emit as all is passing off its other Proton to a nearby carboxyl 8 functionality of aspiring acid I'm so again at relay system Proton comes off here gets passed through an intermediate passed over to this other guy over here this is powerful stuff OK so now the resultant Alcock side is a steeper nucleophile that attack the carbon Hill of reality functionality and turn this stature he joined media and can collapse to give us a high July is of em and bonds but wait there's more but of course we now have a covalent intermediate where this series of the enzyme is stuck as an ester to a fraction to about half of the hydro haven't gone and so the enzyme does is it turns on this machinery and this time it operates to hide your wisest Esther functionality giving you arm in the air and 8 returning us to a series of functionality and giving us a carboxyl later on as the 2nd half of the high July them advice this is pretty cool chemistry I'm sure you chemistry where we're seeing a charge relay system and there's a lot of Soltys here than a penny glossing over but in the end this is a very effective cutting machine this guy gets out there and it's like Edward Scissorhands going to town this thing just starts chopping apart and in fact it's working right now on your stomach making up my stomach I'm kind of hungry but if you have something in your in your stomach animals proteins these guys are at work chopping apart those proteins as we speak right now
this is the part that absolutely amazes me astounds me and you know keeps me dreaming at nite but this is the catalytic triad that close so check this out but in this case I showed you the areas that the same thing I showed on the last line the truth is that these areas are kind of an approximation that we use and instead a better picture of better depiction of this would be a happy hydrogen bonds between the 2 of this series functionality to the histidine into the corporate carboxyl gasses the problem is the hydrogen bonds takes all the joy Out of aero pushing they stuck out the marrow of what makes it so fun to push heroes and said protons and electrons flying around and say this is an accurate depiction of this residence structure is inaccurate appear this equilibrium in accurate depiction but I like drawing it like this and I am so the convention that were going to use is an understanding that will we like this we have 1 step that once that is occurring in a concerted mechanism with 1 fell swoop swoop OK so this is a government bond here takes a step waits a little while .period here now instead of this thing is with 1 fell swoop stepping over and doing the whole reaction all at once
I'm here will supersede produces it pains me to do this the fascinating I'd like you to read about this topic in the book but these are illegal to Our at something that we saw is that many producers had April enzyme army that protects them from turning on until an appropriate time and this is especially important for the Proteas is implicated in a blood-clotting cycle because you sure as heck don't want your blood clotting before and you know at random times during the day right there would be a disaster and so on we saw that the peptides the in the pro-am science can be very effective at blocking the active site for this reason proteins in general are very interesting as blockers of produce active sites and these are found in the bloodsucking animals of the world but these are things like just takes vampire bats and when these little bloodsuckers grab onto you fear there you know they got the things they would rather not be punctured the stuff in the blood and they want to prevent blood coagulation right there trying to prevent blood clotting in the blood clots that don't get a tasty dinner and so on they've evolved inhibitors like this 1 that blocked the active site the paradox here is that of course courteous is equally evolved to chop of properties and so the real trick of these types of inhibitors these protein-based prettiest inhibitors is that they get into the active site but the stayaway From the catalytic triad that I showed earlier which is sort of highlighted here a little hard perhaps but it's in there and so by keeping back but they managed to avoid getting high July's yet they take advantage of the abundant molecular recognition opportunities that stand in this this protein from end to end zoom all the way around it and doing that gives it a very tight fighter and that's critical right at the time at these things aren't really typewriters of the producers it's game over and the boards of the animals going to go hungry all right said this is and this is the kind of thing that interests chemical biologists because it gives us control over enzyme activity were really interested in developing inhibitors of proteins and enzymes that allow us to have the inhibitor at a specified point shot off its activity and then on the study what happens this gives us a powerful tool for figuring out the function of that protein inside the cell and so I can't give you some
examples of covalent or mechanism based protein pretty inhibitors are often irreversible not always on and here is 1 example of this is a call for a metal Tito take notice sky-turned comical functionality and its positions beautifully this electrical like chloral methyl substituent right up close To the nucleophilic city functionality and it also has 1 the the key terms which can act as an elector pile to track this series Alcock side so the Serie nite Alcock side doesn't looking carefully at things thinks this is a common bond and then gets in there and goes to town and attacks because that's what it was the vaulted him into the tax they're giving it attaches neutral intermediate which find very effectively to the enzyme but at the same time the scorer Mattel is positioned neatly Prince Hassan to reaction in Essen to attack on this metal functionality this methylene functionality over here giving us another covalent bonds and so in the end of this enzyme shut down it can't do anything it's got a covalent bond to the side and a covalent bond over here and it has to be the enzymes in a barracks bearer of beer has gripped it's it's totally stop it's not going anywhere this is game over for that were inside OK so it turns out that because these enzymes have such nucleophilic functionality and there are many ways of inhibiting enzymes that take advantage of this nuclear Felicity and do this using superb electrified OK so it's lecture I'll meets nucleophile and it's like the yin and the yang of chemistry magic happens and we see in addition so let's take another look at best and here is a related reaction this is a serious Esther is that hides realizes this a single Collier cases here a pseudo Coleen over here a single is found in synopsis between your nerves at junctures between nerves it's 1 of the ways the nerves talk to each other and it's 1 of the ways that you can actually you move around a case the fact that I can move around its students locally and on it turns out that the enzyme that in here that breaks down as CEO Colleen high July's as this Esteban right here OK case of will enzyme comes and sits a soft shuts down the Coleen from signaling yeah and and I should say that the mechanism for this is very similar to what we saw we talked about serious terrorist action in the previous life still lies here but check this out there is a series of bomb incredibly toxic really new electoral files that get into this enzyme active site and permanently capping and shut off and the problem there is that now you have no way of Hydra lies in Esther of a-Si locally and that is paralysis peso here's what I'm talking about talking about a series of nerve agents These are things like Saran Tavern the access these insanely toxic and electric piles that get into the that here's the Alcock here's the electric and in the end we have a covalent bond to that series of nuclear file the fact is -dash case that's why these innovative scores that you're paralyzed you can't get your muscles to move the take jihad beating and on its came over 4 years and that's why these common compounds are so dangerous and scary and so this is a quick overview of a searing radiators and for that matter catalysis of the hydrolase tells by the hydrolase class of enzymes I wanna switch gears I want to talk to you next about enzymes that use factors sometimes called vitamins and this is the way that proteins expand functionality beyond the 20 naturally occurring amino acids if we had to rely on more if if the enzymes had to on the 20 naturally occurring amino acids that I get a life would be boring they they would maybe they do it up but the truth is these other functionalities that act as Co factors pointed enzymes participating catalysis these scope accuracy vitamins for dramatically extend the abilities of enzymes that catalyze reactions that they otherwise would be capable of catalyzing and other amenities are familiar to you now especially if you take a multivitamin tablet every day and you know the the vitamin B use your at yesterday's are a bunch of vitamin B of showing on the slide over here and what we assume many take a quick look at an example of this year's
1 example of this is
vitamin B 3 this is nature's sodium Borel hydride this thing works great as white as the nature study bright-red will get but Sigmund alters didn't exist back when jurors working this stuff out but equally important way for a hydride aluminum hydride this things aren't exactly stable water unless it signed worldwide because of fired high drives not sustainable water so this evolved as a hydride source that is still stable in the good old each up writes a check this out with this enzyme does is down alcohol ethanol I'm down to Assadullah enzymes called alcohol the hydrogenated and it relies on this vitamin B derivative called any DH or is that the energy plants OK and In doing just this this breakdown of alcohol is absolutely critical by the way this is the same alcohol that you find in these big mouth malt liquor OK that's the stuff this is the stuff that you fraternity friends of drinking while you're out study on Saturday nights of this stuff works as you know it is toxic to humans ,comma causes all kinds of problems we talked about that before and so this is the reaction that detoxified alcohol the 1st step in the campaign to detoxify alcohol and make stuff go away so that it disappears but in order to do this the enzyme has a remarkable transformation that I want share with you always experiments worked out by the great Frank Westheimer about 50 years ago and end up back in the day when he's working this stuff out it wasn't exactly clear whether enzymatic catalysis should be stereo systems that is the reason really for a reaction like this was a trivial reaction relate to evolved to be serious specific it it turns out it is serious this effect and unleash a new area so if you feed the enzyme alcohol that has to deuterium the next you know just deuterium snacks to each other and we'll end up with 8 due to a deuterium added please specifically in the president Abbas's but has won deuterium and noticed the deuterium is coming out toward us pace of just imagine that interior coming out toward us right now if you take this stereo synthesized in 88 and feed to this enzyme ITT hydrogenated lactating hydrogenation uses this as a starting material and to to do this reaction on the wanted list molecule over here and so what's happening years that the interior gets serious specifically inserted into 2 when it reduces this and Teton functionality so what ends up happening is you get perfect stereo specificity for this 2nd reaction over here and this is beautiful stuff OK this makes my heart go pitter-patter here's what what we're seeing in this very elegant experiment is that enzymes are pulling off hundreds of one-way and then delivering them in that in another way and they're doing this with perfect stereo chemical fidelity every time OK let's take a closer look to try to understand that when we look very closely at the time the details of what's going on actually everything I just told you totally makes sense more pitter-patter of the origins here this is the active site of alcohol the hydrogenated fats enzyme measured on the previous slide but there is no easy environment in the active site misses a acts as usual as a U.S. acid and here it is merely you know tied together with 2 Systemes history up here and so this is a grabs on to the alcohol so it's going to form a nicely Lewis acid arrangement with the oxygen of of the alcohol over here and the UN vitamin B 3 derivative NAD +plus is present but it's station below there a and below where the ethanol and molecules going to in OK so this is playing down here a period there's a balance between the 2 we have the ethanol and so when the hydride pops off the ethanol it has no choice but it only has 1 rout available to it it's going to go Hoppen down here in down here and it's going attack specifically in the time that top face of this NAD +plus check it out as it's going down here it's like you know this is this is on a you know a water slide at Raging Waters of something it doesn't have any choice to go in some other direction it's stuck in the shoot and so because it's true it's directed its stationed in a particular arrangement the geometry is such that it only gives you a hydride that's introduced over here the reverse reaction is equally called the reverse reaction has but also serious specificity is going to every time pick up behind tried from the top face don't need top bases available bottom-placed not available but base available and that's really the key to understanding the observations that Frank West made and the beauty of this to summarize the beauty is that this gives us the anatomical detail the precise mechanism for understanding why it is that enzymes catalyze reactions wisteria chemical fidelity then again this is enzyme doesn't have to be stereo chemical you know perfect every time but involved to be and that's more or less what we're going to see time and again OK so again I'm here we see vitamin B 3 extending the functionality of native enzyme that's pretty cool and here's another example this is a friend
of mine called vitamin B 6 tasty little bugger this guy but does all kinds of reactions it's it makes cameos in all kinds of different enzymes here and there and every time it's providing crucial functionality that of quit the enzyme with abilities that it otherwise would not be able to acquire and the a of examples of this distance of a D carboxyl Asian reaction in this case in the enzyme active-site the and B this paradox of prostate boards the ship base With the it with an amino acid and that sets you up for this game carboxyl Asian reaction within acid is decomposed and this happens for example glutamic acid deformed gather the neurotransmitter this is the sort of thing that goes on that takes place in an hour a lot of different cases of here's another 1 this is hydroxy metal transferring this is amino transferees noticed in every case the era is ending up on this carbon over here OK so we're going to build up some negative charge on this comment but that's adjacent to the ship based in here probably wondering where those electrons Korea really really immediately and really hang out there what's so special about it does something it's tuition based well but the ship bases are analogous to Carbondale said check this out the electrons up here that's a negative charge that results from each 1 of these areas the electrons appear can hop hop hop hop hop all the way down to the positive charge down here check this out as a resident structure again pop in the end the bounced way all the way down to the positively charged nitrogen which we know doesn't like having positive charge its electoral negative and the net effect is that this has this stabilizes this negative charge up there it makes this reaction possible otherwise this reaction is not going to go no go there and so on this is really powerful chemistry and it's no surprise to us that it should be no surprise to us that this makes multiple multiple appearances man I want you be
box Lajunen a little greater detail but here we have a this is on the decay of isolation of a hydroxyl tyrosine call dope to give us the opening of the famous of course by the fantastic movie Awakenings starring Robert De Nero Yemen's inevitably yield yourself rented especially wanna onto medicine OK so check this out again we appeal peak in Lebanon to the Nino acid using the shift scandal that we talked about earlier and now what's happening as we do the carboxyl Asia we get the negative charge and electrons bounced bounced bounced all the way down here to be stabilized there's a whole resident structure not showing but it's happening and then but this can they get lies over here to give us that the freedom of OK so shift bases recall are reversible the bond forms the bomb breaks the bond forms the bond rates that sets you up to do a reaction and then released the product over here OK 1 more in the field the world's and I can go on all day and Love Field the publisher you want more this is a really cool this is an example of a transit nation so the user amino acid amino transfer races they take off the Amin from 1 amino acid and then handed off to another and they do that using the the obvious Co factor and this makes paradox opened in phosphate that's the transiting intermediate backgrounds the mean and makes it possible so here we are we have an amino acid it's spelled based as usual In enzyme active-site there's an enemy that acts as a on base d products and we did we see this basic pulls off the alpha proton over here we see it now acting as an asset OK this is this is Jekyll and Hyde kind of stuff right beasts after these assets Geest it cannot make up its mind but by doing this this this kind of versatility and reactivity equips the enzyme which really powerful abilities OK so here we go with this over here acid over here that gives us a new ship based check this out now when we high July is this guy we now have lost the year mean that used to be on the amino acid this gives us a new features again should face acting as a reversible functionality and end up doing all kinds of cool chemistry I think they are probably wondering what happens to this now weird PKP this PAP shown here I can then be used as a means sauce with the key to a different he tells a different veto asset that then becomes an amino acid press so in this case we see that getting start-and transient Lane as P a P and then it has off to another amino acid did form another
amino acid it's at this point I usually ask you if you have any questions but I imagine urea fuzzy slippers hanging out drinking margaritas or something I don't know what you don't know and I don't think about it but if you have questions you know them to be as usual U.S. appears to come to my office hours etc. But this time change years our changes out touch about protein engineering this is a new field of relatively new field and it has unfortunately of terrible made the name is in a very accurate to description of what involves but it does involve proteins but involves a very bizarre type of engineering services time when I think about engineering I think about you know building buildings or you know engines for cars or something in those cases we understand to an extraordinary degree relayed the properties of the materials that are being used to build the the buildings engines whatever proteins it turns out I uh you know I have made out these floppy materials and were still don't understand all of the aspects of holding all the aspects of moderate nation and so it makes it very hard for us to do Adam by protein engineering it turns out that's actually pretty nontrivial however despite his challenges scientists and doing this for several decades and they've been doing this with the goal of improving protein function and also understanding how proteins work when we take a look at the 2nd example 1st a peso of here is an
example of the kind of mutagenesis that protein engineers do to dissect how proteins were became so In this case but you start with some amino acid side chain and you converted into an alley and you do that you change around the code Indiana results in altered on date was results in mutant protein or protein variants as I like to call on these mutants really should refer to the DNA at the very top no here's what's great about this if you do this mutation you basically remove this hydroxyl right here noticed that notice we use that Idaho now we have enough over OK so hydroxyl stance it basically gives you a way of removing all of those Adams Posavina corridor and so now you can ask what function if any did the hydroxyl group contributed to this thing complicated protein over here you're taking out 16 Dalton's of molecular weight as something it might weigh you know 44 Portilla Dalton's or something and you're asking What is that oxygen really going for it this is a technique that I like to think of as the equivalent of reverse engineering you know about reverse-engineering this is what Mercedes vise of BMW and then you know proceeds to Chacon apart maybe they will move some wire then then asked how does the BMW performances still conditions or whatever the case of reverse engineering is a powerful technique and protein engineers have been using it for years but I've already shown you how human
growth hormone and dying rises the human growth hormone receptor but it too and I also even show you pictures that
look like this 1 of the hot spot of human growth hormone I did not tell you however how it is that we know what we know about how growth hormone works so here's the way this these experiments done by Jim Wells and co-workers at Genentech and what they did was new take all of the very residues in growth world it turns out there 19 of the side chains a growth hormone and the systematically went through and take each of those back to alanine cases in mutation but let's just say phenylalanine to alanine then they ask what is the contribution made by the panel group when they do that they find that only these red residues are actually contributing binding energy mutating these other residues to alanine had no effect on the binding of growth hormone for its receptor In furthermore when these and they saw this beguiling hotspot of binding energy these red residues look like vests and noticed that they have all this height of itself in the middle of the green and then this is ringed by hydro functionality over here can like a core sample of a protein arrange so this teaches us stuff about how proteins work and I've been using it in this class to tell you about how proteins work but on it turns out also practical purposes and this is 1 of the findings of operating a jury trying to engineer proteins that do stuff that they otherwise wouldn't dare go out I mean this is the kind of stuff you find it ran in you in your house and it turns out that he and that that producers have been engineered using the techniques of critique of protein engineering to develop better producers and I'm going to give you 1 example of this so subtle license is a protein but that's had some modest specificity but was pretty broad spectrum and the goal but was to engineer a new variant of satellites license that can go out and clean part in protein and the reason why you wanted do this is you want to have a pretty back chop apart from proteins that Baumstein's on people's clothes OK so you get a drop of blood on your shirt or whatever you definitely want to get that remove right so producers found in these products going and I just literally Edward Scissorhands style start clipping apart the proteins that would otherwise stay in close so I think he was engineering the pockets of applying to the side chains of these prejudices and basically opening them up the giving it more space that extra space means that the satellites and variants can now accommodate a diverse array of different properties and so you know maybe this is 1 day united during parts of pieces that lands on your jacket the next day it's you know on unit chewing apart from other the happens find a scene for so this is powerful and this is used in all 4 wide variety of different products and this is the kind of stuff you don't hear about it's actually superbly useful the problem is I told you the good parts I giving you the greatest-hits turns out very greatest-hits there's probably a dozen total failure of 1 of these that are lurking in the shadows and the reason for this is that most mutations take a perfectly good protein and turned it into the trash OK so most mutations make proteins less functional and other here's a really cool example of that in this example this is stacked with copies nuclear is an enzyme that I just you know an inability to the user's Beazer amino acids that cannot be taught that cannot tolerate mutations every single 1 of these little residents I'm totally resists any substitutions and yellow those are the view that allows some changes they can tolerate mutations and you'll notice there aren't that many yellow residues here the vast majority of below so many mutagenesis does not work so well takes a lot of time which is why I get a natural evolution doesn't happen so quickly you and so scientists have come up with all kinds more powerful ways of introducing mutations we talked about in class we talked about for example elegantly attired directed mutagenesis using quick-change PCR talked I believe about Kunkel base mutagenesis so there are a waste of focusing the mutations in 2 particular regions approaching space and then using evolution as a powerful tool say using fake displayed for for example as a powerful tool to evolve new functions of protein there is also Bloomberg I'm escape that I wanted touchiness about carbohydrates that's all I have to say about Britain's I can talk about it for an entire class but it's 1 of my all-time favorite topics but you know I have other things that need talked about so I'm I really switching gears when now in Chapter 7 and were ready talk about carbohydrates if you're not familiar of carbohydrates if you were software organic chemistry class did not cover carbohydrates I need you to go back and review the chapter on carbohydrates in the textbook that you kept from 1051 or whatever some organic chemistry class at and don't get too wrapped up in all the reactions interested in reactivity and let me show you what I mean by that so carbohydrates are hydrated carbon we've already seen for example those using glucose before but they all have this general formula of carbon with the same number of waters OK so over here 5 carbons and then
find water molecule despite that rather guidelines simplicity the truth is that these things are done complicated but these are you know baffling relates to uh chemical biologists now chemical biologists but many chemical biological find is annoyingly baffling it's really 1 of the frontiers chemical biology is to better understand carbohydrates their properties the reactivity their function in the cell etc. and ends up this is really a challenge really for us they often have complex structures that are difficult to assign for example arrange and before we go any further I need to introduce you to some important nomenclature that we're going to use that you must memorize and we're going to be referring to five-member ratings as during and six-member ratings six-member carbohydrate range as journalists on the use of if there are 5 carbons we'll be referring to the carbohydrate as hunters notice thereby problems here so you can have both the 5 carbon during a string that pensioners and also a period of strength that is also a penthouse OK I don't know you're totally confused here and want to rescue you and you can have 86 carbon taxes that has formed a five-member drink all the Peronist or 86 OK makes sense I hope so that's nomenclature going the following and this is 1 of those extraordinary slides so when I 1st noticed that I was like I don't believe this is true but it is OK it turns out that in the human body is only known no signs of carbohydrate building blocks that it that's a it that's the sum total so it turns out that even some of the ones that you're familiar with plant really found in a Interlagos problems surface itself for example right right does not incorporated right not listed here OK so although there's only 9 you don't have to go out and memorize OK so don't bother us you know learning all the carbohydrate building blocks unless you're planning to go into carbohydrate Blanco biology or Michael chemistry which incidentally I recommend it's really exciting frontiers cool stuff going on current more nomenclature unfortunately we're kind of stuck with the old tiny conventions there's just no way around it so entered Saturday's conventions make a lot of sense they make our lives easier and so you dimension that's kind of annoying but it makes sense and it's easy use and seeing stuff OK and so for example we're going to be referring to this structure as do you it has hasn't our functionality at this tournament over here I also have more to say about that amount check out how much better it is a college good that the call this crazy game which would be the ideal partner what is it with these and health there are said straight up but most carbohydrates found in nature these but the truth is we have some else's as well floating around and so we have to know what funeral businesses the D and health the nomenclature refers to the carbon that's furthest away from the enemy carbon he can American urban highlighted with the dog here is the carbon that has 2 oxygen is attached to it due after what you what accident and and then if we go as far away from an apartment as we can we look at this serious it's are serious and it will get the designation D it isn't ask serious and it will get the designation and you know here's an example where it's not even oxygen over here so is this 1 furthest away are there for it's the this 1 check this out OK it's not even part of the ring the ring is over here it's the way off on its own little crazy side chain doesn't matter because we still look at the serious and that's furthest away from an American administrators are so therefore it gets the designation makes sense good that's reviews now here's the other thing the carbohydrates the Adam Air carbon is subject to some change OK so this is an American urban as will see in a moment can either have an alpha configuration or 80 configuration the alpha and beta designation refers to its relationship with this the setting harbor OK now I don't get confused don't panic it's very straightforward although equals entire so if this 1 is and this 1 is now up down the Egyptian style if these 2 are like this then we're going to have a warrant to designate this as health record with Didier again comes from the carbon furthest away from an American case so is Alf see inside his Beta news her coming out awards as best they can therefore it's going to be called the take very straightforward designation but it does take a little practice to try it out and you know amaze your friends at cocktail parties whatever is 1 of Europe's information it will be useful because it's how we talk to each other and you and I have to be talk to each other using a common language for us we won't know anything about what we're talking about how will now will be listened to your bills to be so this is the nomenclature really it is essential that you learn it
at there is this notion of an America facts the truth is it's very modest so ominous yeah to
really understand carbohydrate reactivity we 1st have to talk about the reactivity of any acid house and so but it turns out that carbohydrates oftentimes are bound to convert Inter converting between 8 and the acid talkin figuration and open Shane configuration and I can offer you 2 different mechanisms for this Inter conversion In 1 mechanism we start with acidic conditions and coordinate the oxygen of the rain OK secretly here and then electrons balance bounce giving us neatly this all the hype opened change configuration of the race conversely we do the same thing under basic conditions but this time we 1st protein 8 hydroxide kicking electrons bouncing bouncing opening up the red paint and there's a 2nd error both cases under that 2nd just refers to a simple proton exchange 19 were about dining about what this tells us that is that no matter what all carbohydrates are susceptible to the reactive Al the form take notice the heaviest a towel has the alibi all bundled up protectively trade the Howell the height is hidden away but after under EU acidic or basic conditions the the hike gets exposure and how the highs are super-duper reactor there electrified this is that it is this is like Coke you know so well it's a lot about that but this is why shivers in general are not so that have floated around the bloodstream where all the highs like this 1 can find reactive functionalities reacted with files and start going to town and performing all kinds of patrol products area and getting off topic but stick back to the topic but I want to talk to you about stability in the rain I showed you the rain come apart and about the 2nd innovations and there it is but there is however a general rule of thumb that tells us whether or not the ring is going to come apart not under general the strain ring wins OK so if it's a choice of forming a Peronist in the case of political work during a string this 1 is going to win cases six-member less strain than by members of this conform neatly and nice cheer configuration this land could form an envelope but still it's not quite as good on the seven-member ring can also form juices we never see this OK that sugar stuff that you it with you that you know if you should reports this morning on the 1st cereal or whatever None of it was in the seven-member we never see this city is severely restrained and is also in tropical heat rate this means that this carbon over here that's flopping around in the breeze has to somehow get a to up close to the the Elder High Cotton and it's too far away so entropic leaders David Strom Thurmond economically all that adds up to that news the 2 men and start taking a look
at examples of carbohydrates found in biology In and Out no 1 is better at this than the surface coatings of the TB bacteria Michael back to Terium tuberculosis OK so this is now a little schematic view of the outer surface of this bacteria and check this out this guy has decorated itself like you know Christmas is in the eye you know so some country that really likes Christmas a lot for whites because this 1 is totally gone to town as Christmas trees Christmas trees and lots of lights on the bacteria does this to ,comma seeking insists that for 1 thing this stuff holds off the immune system at a distance OK but notice on each 1 of these little polygons is a different carbohydrate a different model secretary a notice that they're linked together into little changes in these genes kind of branch off I and and the linkages of these these among the sack rides are through quite a city bonds that I'll show you on the next flight but what we find is abundant in highly diverse architecture this is doesn't look quite you know a smooth out of service is another surface that's very rough that's incredibly diverse there's all kinds of different chains around here and we're just going to have to do approximations to describe these things this is going to make our lives miserable complicated and it will make your life is really complicated if you wanna city tuberculosis because this gives the TV about a really potent a weapon for avoiding being tackled by the immune system OK so again
only to satirize extremely complicated and extremely complex here's another example of this is that this is 1 example from the self-service check this out so this guy has long Genova over here all kinds of Ranchi .period each branching .period going off in different directions but at the end over here there's a little don't let their sticks that thing down into the plasma membrane this is a spike that wives it straight into the plaza membrane and anchors firmly so this always branched off all this like shrubbery it's cattle waving around out there in space and it's anchored firmly down here it's the 1st stuck firmly into the ground and because it has a slick detail that likes to be down in the plasma membrane and has no choice but to be down by saying this is the schematic diagrams on but students were working account for organic chemist we don't like thinking about things this polygon representation instead word of us would like to do things much more complicated instead we like to look at them at the level bonds and so when we look closely we see this crazy complexity where we have all kinds of eclecticism bonds glycoside ponds and very very complicated the situation so what's a chemical biologists to I'm showing you the worst-case scenario being searching for complicated I wanna step back from of all try to simplify things so that when you see a complicated diagram I guess you don't get all Dalton and steered and instead I just wanna start out Brenda Starr Oslo and then later when you can in these complicated things they won't need as intimidating so let's get started by talking about formation and breakage of like acidic Ponce it's clear these like the bonds are important rate you know this this whole thing is stitch together by quite acidic fonts here's 1 hears 1 year's Ivry single carbohydrate here has like those at once so that should be our 1st priority quaker
City bonds are a eager linkage between 1 Zackariah and another 1 like him and another but when we look at the mechanism for the formation of a war hydrolysis they all take advantage of the fact that the carbon this and carbon is adjacent to another oxygen this sets you up for performing either anoxic Kirby a or a not so you might think of it's safe to say all textbook show you this sodium ions type of configuration and it's not exactly wrong but it's not exactly right here instead of the truth is somewhere between these 2 cases these 2 extremes the 1 case we have a common comic had another case we have something that's even more discussing the car which is oxygen very positive charge were oxygen being elected negative doesn't like having a positive charge In any case this intermediate sets us up for on your hydrolysis or for new alcohol to attack giving us formation of you there a and high July's like city all or a new glycoside spot OK so in every case we're going to kick off either at hydroxide down here on a word that alcohol and that's going to set us up with some possibly charge intermediate that could then be attacked and should make sense to us that this is going to be a tough we've seen a mechanism for this hydrolysis before and I'd like to know remind you of it we saw when we talked about life's Islamic like a glycol cities enzymes in that case and what I emphasize to you was that the nuclear file that was attacking I was going through kind of an S into reaction rate and it turns out is somewhere between us and to understand 1 another words the alcohol that's getting eyes on I that call functionality Hargeisa tenant steps a little further out the door then nucleophile attacking and so well I'm showing you is I'm showing you how we can best like to represent interviewed cases between S and wanted until we show a super-long bonds here and attentive complies are going to have a little more positive charge John here which incidentally makes it all the more attractive for negatively charged nucleophile to come driving in pay and notice too that I'm showing you the substrate of distortion that was the hallmark of mice assigns functionality again the start this wonderful little cozy chair and the shared its port physically and doing that sets you up for this meet backside displacement of destined to reaction peso again lasers signed the pact of chemical biology toss twist this chair and forces it into this confirmation a twisted chair conformation setting up this nucleophilic attack and I'm making this reaction possible I showed you 1 example of it turns out there are many others there many quite Castle hydrant hideaways lasers and it turns out we classify them as the inverting for retaining inverting enzyme was to start over here and averting enzyme converts out of Panama into a beta animal and retaining enzyme keeps whatever exterior chemistry was there so that's been a examined the biggest history hemisphere start you finish with series chemistry OK so there's 2 possibilities here they have 2 distinct mechanisms the move beyond saying that I'm not going to get too wrapped up in this we talked about this before and is so we talked about how To the fundamentals of forming a bond we talked about the fundamentals of breaking 1 of these quite acidic bonds I now want to talk to you about why it is that this matters in terms of diseases have already shown you tuberculosis and fortunately unfortunately I have a great way that tuberculosis can be cured using hydrolysis of Likasi bonds that's a frontier may be sold in this class will be of the which is really instead I would talk to you about the common cold OK which I realized and you realize is 1 of those unsolved challenges rightly notes that it's you know practically a swear word to say Why to get a cure for common cold went to do something useful life and as they knew it would be so easy so here is the closest that we've come out and there is an enzyme called that is a key enzyme in the life cycle of influenza the virus that causes flu this enzyme helps to release the virus from the cell surface of flu infected cells OK so here's the host cell recall and enzymes parasitically takeover the on the machinery of the the cell to produce new zombie copies of themselves and then the enzymes are the virus but on the surface of the cell and after forms of fully-formed enzymes it needs some way of getting off of being released and so this enzyme neuraminidase Cleaves there and the carbohydrate that has it has it firmly held in place so the innovation of neuraminidase has been a key target for influenza and inhibitors and therapeutics ever since I agree with the term chemical biology would in a really long time moved and fortunately we don't have any great solutions to the problem of energy that Soviet look so the
best that we have the things that kind of look like the carbohydrate that getting cleaved by binary minute these are substrate moments we've seen substrate mimics before break the and he was like ET PT except that wasn't the case so here it is a compound called zanamivir are that actually looks a lot like oxalic acid especially went like this when I sleep that it really does kind of look like Selig assets and that's good because by looking like sour gasses it can fit neatly into the enzyme and decide that of all the buying to Salik and then here's another 1 and another 1 called also assaulted the that is actually given to patients as a pro draft Hey said earlier we talked about pro enzymes and I earlier today back but on last Tuesday's lecture we talked about growing signs this concept of an enzyme that same cleaved apart to expose exposes active fragment here we're seeing a proves we have behind your eyes for the cell has the height realized this L. this ethyl ester the functionality and free up the carboxyl gasses in order to have a functional drug in the absence of estuaries the enzyme does not work at fortunately as racism Diamond doesn't and this strategy is a very effective 1 for hiding away negatively charged functionalities that need to be present to make drug function negatively charged functionalities however and affect things like the ability of the drug to pass through the hydrophobic plasma membrane and so this is a way of making that carboxyl at a little more greasy and a little bit rate more readily able to pass through through Idaho passages OK here we see as assumed in view Of the active site of neuraminidase and I'm not going to get through the mechanism because it has a mechanism similar to other White House that we talked about but I'm check this out this is the this compound over here that the carboxyl Cassidy a sultan of our found ingredient to the active site and that they have beautifully positioned in this case I mean I just want to come moment just to gaze in all this beauty so I can't help myself check this out there is is positively charge largely precisely poised above the negatively charged box late that's this after the Ethel and Esther is Hydro ice exposing it and you can see that's absolutely crucial right we have 1 too it could possibly charge challenge to quantity .period jealous of Argentina that are perfectly poised to grab onto that negative charge so if you don't have negative charges that thing is not going bind beautiful stuff the basic tenets of audience while for a while but unfortunately our best shots are on drugs that you take a day or 2 after you get infected and the shorten the length of time you have influence on the real problem is were not so good at recognizing when you have influence if we have a way of knowing yet I you have a couple of viruses influenza the inexperience and give you full-blown you know study flew in a day or so and we would be really effective at treating it but we don't to be that suggests the need for better diagnostics but right now that's changed gears I won't have to worry about only Gocek arrives and we have to talk more about nomenclature these things are getting complicated really fast and what we're going to be doing is going to be referring to the attachments the carbon said attached to each other In parentheses over here and then we will have a three-letter abbreviation that designates the amount arrived the glide him that's being attached to example of this gasses over here that hasn't helped configuration notice is in times of being inside and has helped configuration and then it's a linkage between carbon to and currently ,comma until 11 3 To a collector's functionality lead to glucose functionality 1 in an acid healed because functionality and so on the user can get complicated quickly don't panic don't get all worked up about this especially don't spend any time memorizing all stuff rather I want to just be comfortable with the concept and familiar enough with the concept that doesn't throw you a curve ball but I want to talk to you about how it is that he's long chains of carbohydrates of legal satellites get born of typically the quite Castle transferees class of enzymes uses that by phosphate based as it like a sealed owner of panicked by based I really really like a unit or actually and a kind of based in fact the use unique he should their sites a cheeky variants of some of the US starting material as a way of activating the starting material recall that phosphates are nature's Path Slate armies laid it's nature's leaving group and so this enzyme q coastal transferees as starts with a few Yukos that Yukos is attached covalently To this dive phosphate the diet Fossett is going to be a good leaving group and that set you up for for performing neatly dressed like a city bond over here OK so what's going on hydroxide is attacking this and their carbon and then the prostate is stepping out the door this again is a kind of hybrid that we saw earlier hybrid s and 2 and 1 reaction where the GDP and functionality is starting to step out the door a little more quickly than the hydroxyl was acting as an innocent to nuclear file to attack but it's kind of a hybrid of the 2 similar the transition state what we've seen earlier let's
get into the mechanism a little bit more here said a picture of an enzyme that actually does this reaction and then here's what it looks like an active site pure beauty isn't but in this case we have hydroxyl need be poised above the and American above this and their carbon noticed that this guy is set up the the 4 backside displacement of you know all the orbitals neatly wine but this but Sigma star orbital is precisely position traveling here is and here we Norway and nucleophilic plane attack this Americana I love this kind of stuff is purely the inaction of OK now what is
good for what this is good for is it sets us up for building really complex structures out of carbohydrates and some complex structures are kind of familiar to us this top 1 it is cellulose cellulose is nothing more than good because you know the sweet stuff that tastes of that yet its workers accepted it joined by Peter Gallegos said it wants a case of the stubbornness that was because stuff that's actually a it's actually is telling us the cellulose in what is PCs because the problem is of course and the reason why will look at why cellulose doesn't taste so good to us is that we have no way of hydrologic these beta linkages of instead on were very adept at high July saying the Alpha linkages of starch OK shown here starch forms these these helices that kind of wine around each other as a consequence of having this be the linkage cases of beaded like acidic differences between alpha and beta could not be bitter right 1 stodgy things taste good and that's the potato chips cellulose things not so good right you start in actuality right for lending a hand in that taste for you OK so these are ubiquitous forms of carbohydrates found in nature and that of the majority of biomass down on our planet is stored in cellulose soaring starchy forms and so this is totally ubiquitous another beer ubiquitous piled up polysaccharides and I'm calling the polysaccharides because they just really long chains of glide against another very ubiquitous polysaccharides is tighter so kind is that Aldus excess skeletons of all of us insects shrimp of across stations right and I don't know about you but when I eat shrimp I'm 1 of those people usually peels off the appeals or spit them out but I don't like chewing on them I don't like giving them but I do have friends that for whatever reason they the shrimp with book the peels and everything the truth is they don't get any nutritious benefit out of those feels OK because Titan is in the adjustable to us it's actually be as a nitrogen analog of some of us starch should actually has the same linkages but it has this he'll functionality attack that replaces the hydroxyl of newcomers and said no and all those exoskeleton of arthropods it's not digestible to humans we do not have functional kite aces in our stomachs this is really doing that because actually this would be a great source of energy and it's very likely that humans are our human ancestors the I'm not you know Homer City humans but the way distant ancestors to us actually probably were capable digesting the sorts of shell so exoskeleton things and we could see evidence of this when we look at the human gene we can see nonfunctional kind bases there still carried along which again suggested diet that are ancestors a that was very rich and bugs so it's very likely reading all kinds of but things and maybe we had a functional candidates that will allow us to digest the and get energy out of it Eric Moore
these are not 50 years now want talk next about a legal step rights but a legal separation better defined as being part of a much more determinedly of the more determined its structure were polysaccharides are a little less determined but here's the 1st example miniature you this is the writers found in need joint OK this is the public sack that Buba Casey's joints and makes it possible to have a bone on bone stuck without maligning apart the bones after 30 years OK so Ohio around is synthesized as a continuous extrusion on the cell surface of the cells that are found near strike of its synthesized by Contra sites and forms as we're gel-like cushion case so in this case what's happening is were starting with the UDP the precursor and much as like what I shared with me I GDP precursor on the previous slide the unique he's just a superb needing great and so unique he stepped out the door and a new quite City bond forms and this basically gets extruded by the Contras sites straight off into the strait region and this gives us and a nice Ohio around jail that cushions the joints what is it about this that cushions joints OK well I don't think it will come as any surprise you to find out that this stuff is very water soluble London abundant opportunities for hardship bonding hegemonic here hegemonic down here the carboxyl functionality is very nice as well lopsided demanding that carbohydrate functionality also pushes the strands apart from each other this makes a nice cushion and it's a nice little watery layer and that soaks up water and it's very stable erekat alone last fall out of the day quite costly to produce so I've been showing you carbohydrates kind of free-floating what we find that we look carefully itself is we find the shrubbery of costly produced all over the place on our surface of cells and when we come back next time I will be talking about all of the abilities at this endows sells less so when we stop here look forward to talking to you when I get back from Rio


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