Zwitterion - Online Tutor, Practice Problems & Exam Prep

Amino acids predominantly exist as zwitterions at physiological pH (around 7), characterized by a dipolar structure with both positive and negative charges. The pKa values for the amino and carboxyl groups are approximately 9-10.5 and 2, respectively. At varying pH levels, the predominant structure shifts: at pH 1, both groups are protonated (net charge +1), while at pH 12, both are deprotonated (net charge -1). Understanding these concepts is crucial for analyzing amino acid behavior in different environments.

Zwitterion

So now that we've talked about the groupings for all 20 amino acids and each of their individual R groups, we're now going to talk about zwitterions. It turns out that the common backbone for all 20 amino acids is predominantly a zwitterion at physiological pH. And recall that physiological pH is right around a pH of about 7. Also recall that when we say predominant structure, what we really mean is that this structure is in the highest concentration among all the other types of structure. This fact here is actually going to become a common known fact, that's going to be part of our basic knowledge of amino acids, even though it might be new information to you right now.

A zwitterion, by definition, is just a dipolar molecule that bears or has two groups that are oppositely charged. The charges on those two groups are a result of acid-base reactions, or H+ transfers or proton transfers. In our example, notice that we have the common structure for all 20 amino acids. So we have our alpha carbon in the center here, we have our central hydrogen, we have our carboxylate group on the right, and our amino group on the left, and then down below, we have our R group. What you'll also notice is that the two groups bearing charges are highlighted. On the left here, we have our amino group, which notice has a positive charge on it, and then on the right, we have our carboxylate anion which has a negative charge on this oxygen shown there. Because there are two groups that have opposite charges on the same molecule, this is a zwitterion. The backbone of all 20 amino acids is a zwitterion, specifically at physiological pH, which is right around pH of 7. This is again going to be common knowledge that is going to be very basic knowledge that we'll be referring to throughout our course. It's good to get this introduced.

We'll be able to get a little bit of practice utilizing this concept in our next practice video, so I'll see you guys there.

Which shows the proper structure of Leu at physiological pH?

• A.
• B.
• C.
• D.

Zwitterion

So in our last lesson video, we said that the predominant structure of the amino acid backbone is a Zwitter ion specifically at physiological pH, which is a pH of 7. But the question is, what is the predominant structure when the pH is not at physiological pH? Like if the pH is 1 or 12, how do you then determine the predominant structure? Well, it turns out you already have the knowledge to be able to answer that question. In this video, I'm mostly just going to be refreshing your memory of older information that we already covered in our previous lesson videos. The first piece of information that I want you to recall from our previous videos is that the pKa is a quantitative measure of the strength of an acidic hydrogen. The greater the pKa value is, the weaker the acid will actually be.

The way we determine the predominant amino acid structure is by independently comparing each pKa value to the pH of the solution. When we independently compare each pKa value to the pH of the solution, we can determine the predominant amino acid structure at any given pH. Notice below, we have the same chart from our previous lesson videos that explains what we mean by comparing the pH of the solution to the pKa of the acid to determine the predominant species, and whether that species is protonated or not. We'll be able to refresh our memories on how to use this chart later on in this video.

In this video, there are only 2 new pieces of information that I want you to know. The first is that alpha amino groups, or amino groups that are part of the backbone of an amino acid, have pKa values in the ballpark range of about 9 to 10.5. The second new piece of information is that alpha carboxyl groups, or carboxyl groups that are part of the backbone of an amino acid, have pKa values that are in the ballpark range of about 2. Knowing these ballpark pKas is important because your professors expect you to know them, and they're going to be really helpful for us as we move forward and solve practice problems.

Notice that we have this graph up above here, and this graph is color-coordinated to the predominant structures that we see down below. You will see that this green predominant structure corresponds with the green line up above in our graph. The blue predominant structure corresponds with the blue line, and the pink predominant structure corresponds with the pink line. We will first fill out these predominant structures down below, and then we'll come back up and look at our graph and see how it relates.

In the center of our image here, we have the same exact image from our previous lesson video. We can see that the pH is right at 7, which is physiological pH, and the predominant structure of the backbone is a zwitterion where we have a protonated amino group on the left with a positive charge and a deprotonated carboxyl group (carboxylate) on the right with a negative charge. This positive charge cancels out with the negative charge and the backbone bone net charge, specifically at pH 7, is going to be 0.

Now if we take this pH of 7 and we drop it down to an acidic pH of 1, then we're going to need to use our previous knowledge to be able to determine the predominant structure, and we're going to have to independently compare each pKa to the pH of the solution. Notice that we're given a pKa for the amino group of 9, and a pKa of the carboxyl group of 2. So starting with the amino group, notice that the pH of 1 is less than the amino group pKa, which is 9. When the pH of the solution is less than the pKa, that means that the concentration of conjugate base is less than the concentration of conjugate acid, and the conjugate acid will be predominating. The majority of the molecules are going to be protonated and have an additional hydrogen. We can expect our amino group to be in the protonated form, which is the NH₃⁺ form, and we'll have a positive charge.

If we do the same for the carboxyl group, notice that the pH of 1 is still going to be less than the carboxyl group pKa, which is 2. Again, when the pH is less than the pKa, the concentration of conjugate acid will be greater, and the majority of the molecules will be protonated. We can expect our carboxyl group to be protonated, and the protonated carboxyl group is just going to have an OH at this position, which is going to be neutral. Notice that we only have one charge here when our backbone is at a pH of 1. That means that the backbone net charge is just going to be plus one at a pH of 1.

Now, if we go ahead and increase the pH all the way up to a pH of 12, then we can perform the same strategy. Notice that when the pH of the solution is equal to 12, that is going to be greater than the amino group pKa, which is 9. When the pH of the solution is greater than the pKa, the concentration of conjugate base will be greater than the concentration of conjugate acid. That means that the majority of the molecules are going to be deprotonated and have one less hydrogen. We can expect our amino group to be in the deprotonated form, which is going to be the NH₂ form, which has no charge on it.

We can do the same with our carboxyl group, and so when the pH of the solution is equal to 12, that's still going to be greater than the carboxyl group pKa, which is again 2. Again, when the pH is greater than the pKa, the concentration of conjugate base will be greater, and the majority of the molecules will be deprotonated. We expect our carboxyl group to be deprotonated. The deprotonated carboxyl group is going to be a carboxylate anion, which has a negative charge on it.

Notice that when the pH is 12, the predominant structure of our backbone only has one charge on it, so that means that the backbone net charge is going to be negative one at a pH of 12. Now, we can go ahead and relate these predominant structures to our graph up above, and you can see that when the pH is 7, right around physiological pH, that corresponds to our x-axis here, the pH of 7, right at this position. You can see that most of our molecules are going to be in the zwitterion form because the concentration is at its highest here. The zwitterion form has a neutral net charge of 0, like we indicated down below.

Now if we go ahead and drop the pH down to an acidic pH of 1, that will correspond right here, and you can see that the majority of our molecules, the highest concentration is going to be where both groups are protonated. You can see that when both groups are protonated in our backbone, the backbone has a plus one charge, and that corresponds to this pink line right here. Then, of course, if we take our pH and we increase the pH all the way up to a pH of 12, that's going to correspond right here on our x-axis, and you can see that the majority of our molecules are going to be in the deprotonated state in this blue that corresponds with this blue line here. Both groups will be deprotonated, and when both groups are deprotonated in the backbone, our backbone has a net charge of negative one.

This concludes our refresher on our lesson here, and we'll be able to utilize these two new pieces of information in problems moving forward. I'll see you guys in those videos.

Zwitterion Example 2

Alright. So here's an example problem that says, "Which is the predominant structure of valine at pH 2?" We are given these two pKa1 = 9.62 and pKa2 = 2.32. From our previous lesson videos, we know that valine is a nonpolar amino acid with a V-shaped R-group. All the R-groups in our answer options, highlighted in blue, have the correct structure and V-shape for valine. We need to determine the predominant structure of valine's backbone at a pH of 2. Recall that alpha amino groups have pKa values in the range of about 9 to 10.5. Thus, pKa1 must be for the amino group. Alpha carboxyl groups have pKa values around 2, so pKa2 must be for the carboxyl group.

Starting with the amino group pKa, a pH of 2 is less than the amino group pKa1=9.62, indicating that the conjugate acid form predominates, which is the protonated form, NH₃⁺. We can eliminate any answer option that does not have an NH₃⁺ for the amino group.

Next, we look at the carboxyl group, and since a pH of 2 is also less than the carboxyl group pKa2=2.32, the conjugate acid form also predominates, meaning it is protonated. Observing the options, the carboxyl group in option A is not protonated, so it can be crossed off. Option D, however, is protonated, indicating that D is the correct answer.

This concludes this example problem. We'll be able to get some practice in our next couple of videos, and I'll see you guys there.

Fill in the groups for the predominant structure of Ala at pH 13?

So this practice problem wants us to fill in the R groups for the predominant structure of alanine, specifically at a pH of 13. To solve this problem, we need to recall alanine's R group. Remember that alanine's one-letter symbol is an A in the mnemonic that helps us memorize alanine's group, which is the nonpolar amino acids, just GAVLYMP. Alanine is shown here with an A. Just as A is the first letter of the alphabet and that's easy to remember, memorizing alanine's R group is also easy because it's just a methyl group. We can go ahead and put in our methyl group here. Now, all we need to do is determine the appropriate charges for the two ionizable groups, the amino group and the carboxyl group. In order to do that, we need to compare the pH of the solution to the pKas. But we're not given the pKas, so we have to remember the ballpark ranges for the amino group pKa and the carboxyl group pKa. Recall from our lesson video that the amino group pKa ballpark range is between 9 and 10.5, and the ballpark range for our carboxyl group pKa is approximately 2. We can now independently compare the pH to each of these pKas. Let's start with the amino group. The pH is 13, and a pH of 13 is greater than the pKa of about 9 to 10.5. Recall from our chart in our lesson video that when the pH is greater than the pKa, that means the conjugate acid is smaller in concentration than the conjugate base, and the conjugate base predominates. The conjugate base of an amino group is just going to be NH2 with no charge. We can go ahead and put that in over here NH2 with no charge. Now we can do the same thing with the carboxyl group, compare the pH, which is a pH of 13, and we'll realize the pH is greater than a pKa of the carboxyl group, which is about 2. Again, when the pH is greater than the pKa, the conjugate base predominates, and the conjugate base of the carboxyl group is going to be a deprotonated carboxyl group, just having the O- on there. We can put in O- here, and now we've got our carboxylate group. This concludes this practice problem. If we wanted to determine the overall net charge, all we need to do is sum up all of the charges. There's only one charge on here, with the carboxyl group, and so it's just going to have an overall negative one charge. This concludes this practice problem, and I'll see you guys in our next one.

Fill in the appropriate groups for Asp at pH 4.3.

So this practice problem wants us to fill in the appropriate groups for aspartic acid, specifically at a pH of 4.3. And so recall that aspartic acid's one letter code is just a D for phonetic sounding. And the mnemonic to help us memorize aspartic acid structure is "dragons eat knights riding horses." And so the D here represents aspartic acid, which we know is an acidic negatively charged acidic amino acid, and it's going to have a carboxyl group in its R group. And so that's what we're seeing here, a carboxyl group, and really, it's just alanine with a carboxyl group on it. In this problem, all we need to do is to compare the pH of the solution independently to each of the pKas. In our previous problems, we only had 2 pKas to compare to, but in this problem, we have 3 pKas. So we have to independently compare the pH to each of the pKas. Let's start over here with pKa1. So pKa1 is 9.82, so that means that it's got to be our alpha amino group because we know the alpha amino group's pKa's range from 9 to 10.5. Let's go ahead and do that one first. So the pH is equal to 4.3, and that is less than pKa1, which is equal to 9.82. And so recall that when the pH is less than the pKa, that means that the conjugate acid is going to predominate. And so the conjugate acid form of the amino group, the amino group conjugate acid form, is just going to be an NH3+. And so that's what we can put into this group up here. We can put in an NH3 and we'll put the plus in red here to make it a little easier to see. Now we can compare this group over here which has a pKa of 2.09, and this, of course, must be the alpha carboxyl group or the carboxyl group that's part of the backbone of the amino acid. And we know that those pKas are right around 2, so it's got to be this one. And so for this, all we need to do is say the pH is still equal to 4.3 and the pH of 4.3 is actually greater than pKa2, which is equal to 2.09. And so, when the pH is greater than the pKa, that means that the conjugate acid's going to be less concentration and the conjugate base is going to predominate. So the conjugate base of the carboxyl group, I'll put alpha carboxyl group, is actually going to be just the O-, the deprotonated form. So it's going to over here, what we can do is just put in an O and we'll put the minus in a different color. Now, we've got these 2 groups, we move on to the R group pKa, which is pKa3 here. With pKa3, we're going to do the same thing. We're going to compare the pH to the pKa. So the pH hasn't changed, it's still 4.3. And a pH of 4.3 is greater than pKa3, which is equal to 3.86. What that means is that when the pH is greater than the pKa, the conjugate base is going to predominate. So this is another carboxyl group. It's not an alpha carboxyl group because, remember, alpha means that it's part of it's extending off of the alpha carbon, which is this carbon right here. And so, this one is a carboxyl group that's in the R group. With this carboxyl group, the deprotonated form, or the conjugate base form, is going to predominate, so it's also going to be just an O-. So we can put in an O here with a minus on it. All we need to do now is place all the appropriate charges in each of these groups. To find the overall net charge, all we need to do is sum up all these groups. We've got 2 negative charges, so that's -2, and then we've got one positive charge, so that makes it -1. So the overall net charge is just -1. And so that concludes this practice problem, and I'll see you guys in our next video.

Draw the predominant structure of Arg at pH 6.5? (pK _a1 = 9.04, pK_a2 = 2.17, pK_a3 = 12.48).

So this practice problem wants us to draw the predominant structure of arginine specifically at a pH of 6.5. And then it goes and it gives us the 3 pKas for arginine's ionizable groups. And so recall that arginine's one-letter code is R, and the mnemonic that helps us memorize arginine structure is dragons eat knights riding horses. And so the R here is arginine. And so arginine's R group has components of both lysine and histidine, and we'll get to its R group after we start drawing the predominant structure. So, we know that when we're drawing an amino acid that there's going to be an amino group. So let's put the amino group in a dotted box here because we'll get to it shortly. And then we know that there's going to also be an alpha carbon and a carboxyl group. So we know there's going to be a carboxyl group. Here's the alpha carbon. And then this over here is going to be the protonated carboxyl group. So we know that in here is going to be either an OH or an O- group. And so with this alpha carbon here, remember that the R group has to be going down and dash. So remember that for the R group, when you're drawing an L-amino acid, so we're trying to draw an L-amino acid, that the R group must go down and dash, so R D D. So it has to be going down and dashed. And so, let's get that out of here. And so now that we know that, we have to have a dash going down for our R group to get an L amino acid, this is going to be the overall structure of our R group. So now remember that just like arginine's R group, has 3 pointy ends on it, so it has one pointy end here, one over here, one over here because it has features of a sword. It has 3 pointy ends that you could really try to poke somebody with. Its R group is going to have a 3 carbon start to the chain, so it's going to have a CH2, another CH2, another CH2. And then it's going to have a triangular structure, so the three points also help you remember a triangular nitrogen structure. So the way this structure works is there's a nitrogen, a carbon, and another nitrogen, and this carbon is double-bonded to another nitrogen. And so then you just fill in the hydrogens. This one's going to have 1, this one will have 2, and this one is also going to, well, we're not sure how many it's going to have because we're trying to figure out if it's charged or not. So it's either going to have 1 or 2, so for now, we'll just leave it as an H until we figure out if it's going to be charged or not. So now that we have arginine's R group mostly filled in, and we know that the amino group is going to go over here, so we know the amino group will go here and the carboxyl group will go over here. Now, we can start to compare the pH of the solution, which is given to us as 6.5 to each of the individual R groups. I mean, each of the individual pKas. And so what you'll see here is that pKa1 here must be for the amino group because pKa1 has a value of about 9, and we know that the alpha amino groups, which are over here, have to have a pKa of between 9-10.5. So pKa1 must be this guy over here, so we'll put pKa1 over here. The carboxyl group, which is this one over here, must be pKa2 because pKa2, we know that alpha carboxyl groups have to have a pKa of about 2, so that has to be this one. So we'll put that in green right next to it, pKa2 is this one. And then the pKa3, of course, has to be the one for red. So this has to be for the R group, which is down here. So we'll go ahead and put pKa3 over here. So now we just again compare the pK pH to each of the pKas. We can start with the blue over here. So the pH is 6.5, and a pH of 6.5 is less than a pKa1 which is equal to 9.04. And when the pH is less than the pKa, what that means is that the conjugate acid is going to predominate and the conjugate acid form of the amino group is an NH3+. And so we that's what we can put into this group over here. We can put in NH3 and we'll put the plus in red just to make it a little easier to see. Now we can do the same and compare the carboxyl group, pKa to the pH. So the pH is still 6.5, so pH is 6.5, is greater than pKa2, which is equal to 2.17, right here. And so again, when the pH is greater than pKa, what that means is that the conjugate acid is going to be lower in concentration and the conjugate base is going to predominate. And the conjugate base of the carboxyl group here, so the conjugate base is going to be a deprotonated carboxyl group, so it's just going to be an O-. So in here, we can just put in an O- and we'll put that there. So now, the last thing that we need to do is look at, compare the pKa3 to the pH. So again, the pH is going to be still equal to 6.5. And the pH of 6.5 is actually less than pKa3, which is equal to 12.48, shown up here. And so when you have, again, the pH is less than the pKa, what that means is that, the conjugate acid is going to predominate. And so the conjugate acid form is going to be protonated. And so that means that this, nitrogen here is going to have indeed 2 hydrogens on it and it's going to be protonated. And so now we have all 3 of our groups in the appropriate charges, so we have a positive charge on the amino group, a negative charge on the carboxyl group, and a positive charge on the R group. So 2 positive charges and one negative charge comes out to a net charge of just positive 1. And so that concludes this practice problem. We've drawn the structures, and, we will see you in the next practice problem.

At what pH would an amino acid bear both a neutral -COOH and a -NH ₂ group?

• A. Between pH 0-5.
• B. Between pH 5-9.
• C. Between pH 9-14.
• D. Not likely to occur at any pH.

Here’s what students ask on this topic:

What is a zwitterion and how does it relate to amino acids?

A zwitterion is a dipolar molecule that has both positive and negative charges on different atoms but is overall electrically neutral. In the context of amino acids, at physiological pH (around 7), the amino group (NH₃⁺) is protonated and carries a positive charge, while the carboxyl group (COO^-) is deprotonated and carries a negative charge. This dipolar nature makes the amino acid a zwitterion, which is the predominant form of amino acids in biological systems.

How do pH levels affect the structure of amino acids?

The structure of amino acids changes with pH due to the protonation and deprotonation of the amino and carboxyl groups. At low pH (e.g., pH 1), both groups are protonated, resulting in a net positive charge (+1). At physiological pH (around 7), the amino acid exists as a zwitterion with no net charge. At high pH (e.g., pH 12), both groups are deprotonated, resulting in a net negative charge (-1). These changes are crucial for understanding amino acid behavior in different environments.

What are the pKa values of the amino and carboxyl groups in amino acids?

The pKa values of the amino and carboxyl groups in amino acids are essential for predicting their ionization states at different pH levels. The pKa of the amino group is typically in the range of 9 to 10.5, while the pKa of the carboxyl group is around 2. These values help determine whether the groups are protonated or deprotonated at a given pH, influencing the overall charge and structure of the amino acid.

Why is the zwitterion form of amino acids predominant at physiological pH?

At physiological pH (around 7), the zwitterion form of amino acids is predominant because the pH is between the pKa values of the amino and carboxyl groups. The amino group (pKa ~9-10.5) is protonated (NH₃⁺), and the carboxyl group (pKa ~2) is deprotonated (COO^-). This results in a molecule with both positive and negative charges, but an overall neutral charge, making the zwitterion form the most stable and abundant at this pH.

How can you determine the predominant structure of an amino acid at a given pH?

To determine the predominant structure of an amino acid at a given pH, compare the pH to the pKa values of the amino and carboxyl groups. If the pH is lower than the pKa, the group is protonated; if higher, it is deprotonated. For example, at pH 1, both groups are protonated (net charge +1). At pH 7, the amino acid is a zwitterion (net charge 0). At pH 12, both groups are deprotonated (net charge -1). This method helps predict the ionization state and overall charge of the amino acid.