hello organic chemistry students in this video we're going to cover the wonderful world of alpha amino acids now this Alpha right here is super important because we can have beta amino acids and other types as well but since we're looking at human or mamalian physiology we are going to be looking at Alpha amino acids now first of all what on Earth is an amino acid and what is Alpha anyway so what makes an amino acid an amino acid an amino acid must be a molecule that has a carbon right here that has both a carboxilic acid and an amine on it so when we're looking at this structure we see a carboxilic acid which is super important to have critical for an amino acid and an amine right here now the carbon that links them together is called the alpha carbon and this should sound familiar because we remember from our class 3 carbonal chemistry that a carbonal that has a carbon directly attached to it is Alpha so there's our Alpha carbon connecting to the carboxilic acid now all amino acids have the carboxilic acid connected to the alpha carbon not all amino acids have the amine attached to it unless you're looking at Alpha amino acids and that's why I was saying Alpha versus beta and other ones are so important in Alpha amino acids the amine group is attached to the alpha carbon that's what makes an alpha amino acid for us as humans now the basic structure for all amino acids I should say all Alpha amino acids and for the rest of this video I'm just going to say the word amino acid instead of alpha but we're covering Alpha only because that's all we care about this is the basic structure for an alpha amino acid in the in our human bodies now notice I'm on that Alpha Center I'm drawing an R Group no stereo Center whatsoever just drawing an R Group there that R Group is going to give the identity for the amino acids now remember in the carbohydrates we talked about how the pattern of the O groups made the name are made for Unique carbohydrates whatever the R Group is is what's going to make the amino acid every single amino acid in our bodies has a carboxilic acid and an amine that's all the same so we don't care about that all we care about is this R group right here that's on the alpha center now there's two types of amino acids that our body that are that are present we have Alpha I'm sorry not Alpha but we have D and L amino acids what does that mean an L amino acid is where the amine group is on the the left hand side of this Fisher projection right here let me go ahead and write Fisher projection and a d amino acid is where the amine group is on the right side of the fisser projection please refer to your textbook on how to adopt the fisser projections from a structure as shown now for us as humans the one that we truly care about are the L amino acids I know in carbohydrates it's D and here it's L I didn't come up with this this is what our body uses please don't get mad at the messenger so we use l amino acids if we consume a d amino acid nothing happens we just use it as fiber and excrete it out L is what our body uses D is present in a lot of bacterial strains but we do not use them ourselves so now we've just covered the basics of amino acids all amino acids have this basic structure right here we can have this R Group coming out of the plane like we see up here with alanine or going into the plane for alanine which would make the D alanine what we're going to cover talk about next is all the amino acids in our body there's 20 of them we're going to talk about the characteristics of the R Group because all of them have the amine and carboxilic acid again and we're going to talk about what makes that R Group unique to each one and then at the end of this we're going to talk about how can we even use these structur in terms of its PKA to isolate them called isoelectric focusing we're going to get there so now with that let's go ahead and get into the full um all 20 amino acids that we have in our bodies but once again Alpha Center carboxilic acid and an amine and the r group right up here in this case it's a methyl group for alanine if this was a hydrogen it would be glycine very important difference now that's the basic structure right there all right now keeping in mind that this is a Global Campus class you have this uh sheet right here available to you and it's inside the module page for this topic so that doesn't that means you don't have to memorize all the amino acids woo now it's a good thing to memorize just so you have them down but you don't need them for this class but for your other classes you might need this so now let's go ahead and talk about what are the amino acids now up above we're going to get into this in one second but I want to go ahead and talk about all 20 amino acids we have three main categories that we can break them down to non-polar side chains charged polar side chains and uncharged polar side chains first of all what on Earth is the side chain that is the r group so when we look at non-polar side chains if we have hydrogen on this carbon we have glycine now notice glycine doesn't have D or L because this is an ayal Center no chirality so glycin is the only amino acid without a d or L nomenclature we look over here and we put a methyl group down we now have alanine that's what makes alanine alanine notice the amine group is the same carboxilic acid is the same looking here we have an isopropyl group and that makes veiling when we have this um um sectoral group right here we we're looking at Lucine when we have this four carbon chain here we're looking at isol leucine when we have this two carbon chain with a sulfide in the middle of it we have methionine and then when it's in a ring form it's called Proline when we have a ch2 in a Benzene ring it's called feny alanine and then finally a ch2 in this indol ring it's called tryptophan notice it's what the R Group is that gives the unique names for these amino acids now why are these all non-polar side chains they're all made of pretty much carbon very very hydrophobic types of um side chains so here very hydrophobic hydrophobic hydrophobic as well while sulfur has lone pairs it's flanked by a lot of carbon chains and therefore hydrophobic let's go ahead and look at some of the other ones so here's 1 2 3 4 5 6 7 8 nine amino acids right here that are nonpolar so I could ask you I could show an amino acid and ask you is this a non-polar charged or uncharged side chain with this sheet right here that's a piece of cake so now let's look at a Charged polar side Chain versus an uncharged polar side chain first of all what makes them polar look at the amount of hetero atoms here here carboxilic acid multiple nitrogen carboxilic acid o an O group an O group an amid an Amid and an O group right there that's what is making these polar the presence of very hydrophilic groups in them now you might be saying wait there's a sulfur here once again flanked by a lot of carbon there's a nitrogen just like we see down here flanked by a lot of carbon that makes this very hydrophobic and it's a non-polar side chain so now what makes the these polar charged and makes these polar uncharged alcohol groups cannot lose their proton in physiological phes so that that proton will never leave so any alcohols not going to leave now here we have an O group on an SP2 hybridized carbon it's not an alcohol it's a phenol group but it behaves like an alcohol and it won't what we call Auto ionize so these hydrogens here let's go ahead and circle them in blue these hydrogens in blue will not leave at different PHS in our body here we have an amid functional group right here which is not going to lose the protons let me go and erase that we're not going to lose any of these protons right here because it's an amid functional group and that goes for the same right here now what about cysteine cysteine and alcohols are very similar to one another that sulfur is not going to lose that hydrogen so all of these hydrogens do not dissociates automatically and we're not going to see them dissociate at physiological ph's so they remain intact so they are uncharged side chains let's look at the other side this nitrogen right here it's not part of an amid could act as a base and pick up a proton that would make it a positive charge lysine's lone pair of electrons could pick up a proton so both of those are charged polar amino acids because we can pick up protons in solution the same thing is going to happen right down here to histadine so any of those charged or those polar amino acids have nitrogens in them that are not amids we're looking at am means they can pick up protons so they can become positively charged remember nitrogen goes from neutral to positive when we pick up that proton but now in lime green here these carboxilic acid protons can be lost in solution leaving a negative charge behind and that's why these are charged side chains because if the pH gets high enough we'll lose those protons very nicely so that's the difference between non-polar charged and uncharged polar side chains over here on the far lower right is just some information about some protecting groups how we name amino acids it's just kind of useful for other classes but I'm not going to be testing you upon Bach groups and anhydrides and how to make these dipeptides all we care we're going to talk about how to make them physiologically not synthetically so let's go back up to the top of the page classically this is the way an L amino acid is drawn notice this is coming out of the page with this up configuration of that Bridge Center if this was going into the page that would be an r or I'm sorry a d configuration now at physiological pH it does not look like this we draw this by convention but at physiological pH an amine is a base a carboxilic acid is an acid and we have a proton transfer this is the way all amino acids look in terms of its backbone let's go ahead and circle that this part right here is what we call the backbone of an amino acid why all of them have that Backbone in common so the backbone of all amino acids at physiological pH is a positive nitrogen negative carboxilate now if we drop the pH of one we're going to see the carboxilate become a carboxilic acid and the mean remains proteinated but if the pH goes to 10 we're going to see the carboxilic acid lose its proton as well as the amine we're going to talk about that on the next page right here we're just laying the groundwork for this now D amino acids is when that group is going back when we have the confirmation of the nitrogen carbon carbon chain notice this carbon's pointing up if I was to flip this molecule let me go ahead and come over here and just do this it's a very simple change notice here how this carbon is pointing down this carbon is pointing up in order to make this an L amino acid that R Group is going into the plane we're just flipping this molecule in space so please do not say oh if the R Group is going back it's D if it's coming out it's l no it depends upon the configuration that it's in so we have to look at how that Alpha carbon is positioned and that's why go back to your textbook and learn how to take these and put them into Fisher projections it's not that bad of chemistry so now let's go ahead and talk about what is happening here with these pH changes on the next slide all right so now every functional group in an amino acid has an ionizable group so we have carboxilic acids amines amids phenols all this fun stuff so what we're going to talk about is if we're looking at Glycine and we don't care if it's D or L the D or L configuration will not change anything we talk about on this slide if we looking at this molecule right here if the glycine was at a pH of 11 what would be the major form of glycine and it would be in this form right here here where we're going to have a protonated Aman and a negative charge actually I'm so sorry let me come back in here for one second I was thinking about a different pH I wanted to do first but I decided to keep it easier it would be a amine group unprotonated and a carbox or carboxilate without its acidic proton whoa how on Earth does this happen in order to answer this we're going to have to go back through some basic concepts from Jen Kim called PKA values so remember a PKA is talking about the ability of a proton to leave a molecule so we have two protons in this molecule yes there more protons on this carbon right here I just care about one of them they're all exactly the same so I'll call this proton set a and this proton set B out of those two proton sets which proton is more acidic so to answer this we have to show both of them in their d prot ated form so I'll draw a here so there's a carbon with a negative charge and if I lose proton B we have an oxygen with a negative charge so what's better with the negative charge carbon or oxygen and the oxygen is byar it can also resonate through the carbonal as can be that's class three carbonal but the proton on the carboxylic acid is more acidic than the proton on the amine which means it has a lower PKA value the pka of proton B is going to be somewhere around 3 to 4 the pka of these protons on the alpha centers are going to be anywhere between 21 and 32 really high so the lower the pka the more acidic the protons are that's a quick little review of PKA from our gen cam so now if the pH actually let me just go ahead and draw this carboxilic and we don't care about those Alpha protons whatsoever so I'll go ahead and just put flines all over this molecule so they only have one hydrogen in question we know that we're going to be able to lose that proton on the carboxilic acid there it is cf3 to save some space this is a reversible process so this is what we're talking about in terms of what PH we're at what is the major population of an amino acid in solution if we look at this and let me go ahead and say I'm just going to make up a PKA value it's going to be pretty close I'm going to say this is three and I just want to keep these the whole values for right now if the pH equals 3 I'm going to call this form one form 2 so if the pH equals 3 that is the same pH as the pka and that means we have the same concentration of one as two we're not ever going to have 100% 1 or 100% 2 we're going to change the populations of them in solution so now if our pH equal 2 the pH is below the pka meaning it's more acidic so are we going to be in the carboxilic acid form or the base form with the negative charge and we will have more of the carboxilic acid form now we're not going to care about the ratio of them in this class not whatsoever technically it's a log based system so if it was one pH unit we're saying it is a 10 to one ratio but that's just showing the MTH there what we care about right now is what is the most populated form of that backbone now if the pH was at four that means the pH is above the pka and therefore we're going to have more of compound 2 than compound one so what we're seeing here is that the pka is going to help us determine is that functional group mostly going to be in its acidic form or in its base form with a carboxilic acid we go from neutral to negative negative to neutral that's it for an amine group we're going to go from neutral to positive positive to neutral why amines are basic they pick up protons carboxilic acids are acidic they donate protons all right let me go ahead and Shrink this down if I can oops not that there we go just so we can keep using that data table right up above so going to put a little box around this right here let's go ahead and look at that first amino acid alanine so here is the carboxilic acid here is the amine group right there now notice there's no PK a right here oops can't see that there's no PKA group or value for the R Group because it is a nonpolar side chain notice all the non-polar side chains have absolutely no PKA values here because you can't lose those protons now also inside this mix here you're seeing some of the oh where is it at let me find one uh searing we're seeing some of the Polar um uncharged amino acids remember it has to be ionizable to have a PKA value so we're not looking at searing we're not looking at pheny alanine because that o group can't Auto ionize so we're just looking at these right in here let me stress one thing really quickly quickly before I forget do not memorize this table you do not need to memorize it whatsoever it will always be provided now the pka values can be slightly different from table to table it depends upon how they were measured so I will always give you the table for the pka values I want you to use you must use the table that is provided you can't find your own so let's go back and look at alanine over here now once again I don't care if it's DL so we're just going to draw a straight line let's go ahead and figure out the carboxilic acids PKA so we come back over here to the data table alanine the alpha carboxilic acid 2.35 the Amine 9.87 these are more accurate values not the whole values I gave you before so if the pH was below this PKA so if we're at a pH of two would this carboxilic acid mostly be in its neutral state or negative State and it would mostly be in its neutral State because we're in the acidic form what I'm asking here is if we look at this molecule right here here's the alanine CO2 and we're looking at the ability AB ility to lose that proton so if the pH was below 2.35 we're going to favor being in this neutral form of the carboxilic acid if the pH is above the pka we're going to be in the negative form of the carboxilic acid let me say that again if the pH is below the pka for the carboxilic acid it's neutral if the pH is above the pka for the carboxilic acid it's negative notice how I'm stressing carboxilic acid very important now when we look at the amine group right here if the pH is below the pka it's going to be in its acid form which is positive if the pH is above the pka it's going to be neutral so let me say that very clearly if the pH is below the pka for the amine it's going to be positive if the pH is above the pka for the amine it's going to be negative so if I can come down here and try to make a general chart so if we're looking at carboxilic acids and amines right here if we are below or above the PK a if we're below the pka we're going to be neutral for the carboxilic acid if the pH is above the pka we're going to be negative negative 1 for the amines if we are below the pka we will be a positive one if we are above the PK the pH we are going to be zero that is the most important thing that's the predominant form of those functional groups so now let me go ahead ahe and just ask a tough question if the pH is at a pH of six for alanine what is the predominant form so we know the backbone is going to remain the same so here's our CO2 here's our NH how many h's we have we don't know yet and I don't care if it's D or L whatsoever so now if the pH is six we are above the pka for the carboxilate right so above that carboxilate is going to be a negative charge ph6 is below the pka of 9.87 for this amine group which means it will be protonated and a positive charge and this is the predominant form for alanine at a pH of six same exact question but now what if the pH equal 1 if the pH equal one the amine is still well below the pka so that is protonated the carboxilate group now carboxilic acid is below the pka so it'll be neutral because the proton is present and that is the predominant form at a pH of one and you can do the same thing if the pH was above 9.87 so when we look at alamine if we wanted to figure out the pH at which alanine actually has a full out zero charge remember at a pH of six right here we're saying this is negative this is positive but we still have some in the neutral form some in the neutral form here we never have 100% never we're looking at a balance right now we want to figure out when we have predominant a zero charge on this amino acid and that's called the pi point and it is temperature dependent how do we figure out the pi point for these amino acid groups that do not have PKA for the side chains we take the average of the pka for the carboxilic acid the pka for the amine add them together and divide by two so the pi value for these is telling us the isoelectric point for that amino acid why is that useful if you have someone who has a metabolic disease and let's say let's just say AR um alanin since that's the one we're talking about right now and we have to quantify alanine in a bloodstream you take a blood sample of alanine from the patient bring it to a pH of 6.11 at 25° the alanine drops out at that pH the amino acid is insoluble and it falls out of solution so this is how we can actually extract and acquire amino acids so that's one very important biological application of why we care about Pi values let's go ahead and talk about now and I encourage you to go ahead and do this for all of these other ones right here that I'm going to go ahead and put check marks in blue so anyone's in blue right here pretty easy to calculate the pi values because there is no R Group that's ionizable on the next slide we're going to talk about one that has an R group that is ioniz ible all right so look at the pka groups of a side chain that is ionizable I'm going to look at Arginine why Arginine it's the second one on the list that's it the attack for this is the same thing for all the other polar side groups now the first thing you want to do is if I'm asking questions about arginine is to draw the relevant structure of it now this is not the full structure of arginine by any means notice it's a big squiggly line I'm not showing the guanidinium group right up here I'm just showing that there's an amine that can become proteinated an amine and an amine that's all I care about the next thing I want to do is come in and write the pka values for each group 2.18 for the alpha carboxilic acid now notice here this NH3 is for the alpha amine and then the r group's Aman is right here under the pka for R Group and that is thir 14.2 now we don't care about that table whatsoever now anymore we have the pka values what I would like us to do is write the form or what is let me go ahead and erase this and let me change this question what is the charge of arginine at a pH h of 8 wow that sounds crazy now it's just what we did on the previous page so let's go ahead and dissect this group by group so I'm going to go ahead and draw the basic backbone once again who cares about the full structure of the R Group the carboxilic acid the pH is above the pka and if it's above the pH of the or the P the pH is above the pka that means it is in a negative States perfect perfect let's look at the alpha amine group right here the pH is below the pka which means it is proteinated and now for the R Group the pH is below the pka so that our group is going to have a pardon me positive charge so what is the overall charge of arginine at a pH of 8 + 1 and that's what we're saying for an overall average so that is how we can figure out the charges of amino acids at different PHS but how do we figure out its pi value it's not as easy as the one that just have two values we have three values here so we have to figure out which ones to use to figure out where we go from negative to or where overall we have a net neutral charge to do this we're going to look at all three PKA values given and we're going to start drawing some different structures of this molecule so let me shrink this down move it up I'm going to first say let's go ahead and draw this at a pH of one y one we're below the pka of the lowest PKA value so at a pka of one and actually I'm going to show you exactly what I would do here this is what I used to do all the time I've now made this little triangle right here which is what we have right here I know the carbox PC acid the pH is below the pka so it's going to be a zero value it's going to have the proton the amine will be protonated and the R Group will be proteinated now we're going to choose a pH between the next two PKA 2.18 9.09 so I'm going to go ahead and choose 7 at a pka of 7 the carboxilic acid will lose its proton the Amin will be positive and the R Group will be positive now let's choose a pH between these two PKA values I'm going to go ahead and choose 10 when we're between 10 the carboxilate is still negative we now have a neutral Alpha amine group and the side chain is still positive now let's choose a pH above the PK of the R Group and I'm going to go ahead and choose 14 the carboxilic acid will still be negative the alpha amine will still be neutral and now the R Group will be neutral when we look at the overall charges we're at a plus two here we are looking at a + one right here we are at a net zero charge right here and then here we're looking at A1 charge so when we look at all these charge states where do we have a net zero charge right here ooh what PKA values were we manipulating or playing with to get to this zero State we were looking at the amine group and the amine group in the R Group so we would take these two groups add them together and divide by you got it two and that's how you come up with the pi of 10.76 I highly encourage you to do the same thing for the other ones just to practice it based upon this chart right here the more you practice it the easier it becomes let's go ahead and do a little bit more of the complex examples of these all right here is a more complex problem but believe it or not the strategy is exactly the same the question here is what is the pi for this dipeptide as shown this is a molecule that contains two amino acids joined together how do they become joined together we're going to talk about that in the enzyme section so we can talk about how enzymes are made and stuff like that the important thing is we have to identify them so we're going to find the amid bond in this molecule which is this right here and the amid bond is what joins the these two molecules together so here is one amino acid right there here is one amino acid right here we have to identify them the one in blue is alanine we can use our data table to find this out and the one in red is a spartic acid now a spartic acid has an ionizable R Group alanine luckily does not let's go ahead and figure out PKA values and the ones that we need for aspartic a acid we look right here aspartic acid's um Alpha am group is 9.09 so I'll write 9.09 now for the side chain of a spartic acid this is a little different than the last one so here's a spartic acid the side chain is 3.65 so here's 3.65 right there now the alanin carboxilic acid is at 2.35 I believe let me just double check that there it is so now we have to do the same thing that we did on the previous page where we're going to draw the different charge States at different pH values about those PKA values up above so we're going to look at ph's at different states here's the backbone of the dipeptide here's the carboxilic acid group here's the amine and so forth and the side chains carboxilic acid I don't even do that I actually get rid of those groups entirely so I don't confuse myself and I just have straight lines so so the carboxilic acid if the pH is equal to 1 1 is below 2.35 so it will be neutral 1 is below 3.65 so the side group will be neutral and one is below 9.09 so the amine group will be positive we're looking at A+ one now let's choose a pH between two of those PKA values 2.35 and 3.65 I'm going to choose three in that the carboxilate the alpha carboxilate acid will be negative the side chains carboxilic acid will be neutral and the amine group will be positive what's the overall charge zero let's look at the next PKA we're going to look at 3.65 and 9.09 so I'm going to choose a pH of s doesn't matter which one as long as it's between it and now what I'm going to do is do the same rationale a ph of 7 is above the 2.35 so that's going to be Negative pH of 7 is above 3. 67 so that carboxilic acid will be negative and 7 is below 9.09 so this will be positive this is now A1 let's look at the pka value above the last PK group of 9.09 and I'll look at 12 right here so when we look at that both carboxilic acids will be negative and the amine groups PKA is below the pH or the pH is above the pka and that's going to be neutral for a minus 2 charge so if that's a minus two charge I don't know why I Circle that that is clearly not going to be where our isoelectric point is we need to be focusing in right here so what PKA values are we between to give us this value pH of 3 we're looking at pardon me 2.35 and 3.65 so to calculate this pi value right here we would take 2.35 + 3.65 and divide that by two let me pull out my trusty calculator 3.65 divide that by two and our isoelectric point for this random dipeptide is three bring the pH to three this am this dipeptide will drop out of solution with that this now covers the amino acid section for this class what we've covered here is how to determine D and L configurations how to know we have 20 different amino acids and what's the name and how are they made it's all based upon the r groups of the amino acids remember all the backbones are backbones are the same we talked about how PKA are used to figure out if it's a neutral negative or positive compound and then to use those PKA to calculate pi values I highly recommend you go back and watch this video again take some more notes on it and if you have questions please feel free to email me come to office hours or come to a discussion section and I'll be happy to help you however I can I hope each of you are doing well and I look forward to seeing you all soon