Question

A typical amino acid with one amino group and one carboxylic acid group, such as serine, can exist in water in several ionic forms. (a) Suggest the forms of the amino acid at low pH and at high pH. (b) Amino acids generally have two pK\(_{a}\) values, one in the range of 2 to 3 and the other in the range of 9 to \(10 .\) Serine, for example, has pK\(_{a}\) values of 2.19 and \(9.21 .\) Using species such as acetic acid and ammonia as models, suggest the origin of the two pK\(_{a}\) values. (c) Glutamic acid is an amino acid that has three \(\mathrm{p} K_{a}^{\prime} \mathrm{s} : 2.10,4.07,\) and \(9.47 .\) Draw the structure of glutamic acid, and assign each \(\mathrm{pK}_{a}\) to the appropriate part of the molecule. (d) An unknown amino acid is titrated with strong base, producing the following titration curve. Which amino acids are likely candidates for the unknown?

Short answer

At low pH, a typical amino acid like serine will have a protonated carboxyl group (COOH) and a protonated amino group (NH\(_{3}^{+}\)). At high pH, it will have a deprotonated carboxyl group (COO\(^-\)) and a protonated amino group (NH\(_{3}^{+}\)). The two pK\(_{a}\) values for amino acids correspond to the ionization of the carboxyl and amino groups, similar to acetic acid and ammonia as models. In glutamic acid, pK\(_{a}\) values of 2.10, 4.07, and 9.47 correspond to the ionization of its two carboxyl groups and one amino group, respectively. To identify an unknown amino acid from a titration curve, we need to compare its pK\(_{a}\) values with those of known amino acids, and further information about the titration curve is necessary.

Step-by-step solution

1. Ionic forms of the amino acid at low pH and high pH

When an amino acid is placed in water, it can exist in different ionized forms depending on the pH of the solution. At low pH (i.e., in acidic conditions), the carboxyl group will be protonated (COOH) and amino group also protonated (NH\(_{3}^{+}\)). At high pH (i.e., in alkaline conditions), the carboxyl group will be deprotonated (COO\(^-\)) and the amino group remains protonated (NH\(_{3}^{+}\)).

2. Origin of the two pK\(_{a}\) values

Amino acids generally have two pK\(_{a}\) values, one in the range of 2 to 3 and the other in the range of 9 to 10. These two pK\(_{a}\) values can be attributed to the ionizable groups present in the amino acid: the carboxyl group (COOH) and the amino group (NH\(_{2}\)). In the case of serine, it has pK\(_{a}\) values of 2.19 and 9.21. The lower pK\(_{a}\) value (2.19) corresponds to the carboxyl group, and the higher one (9.21) corresponds to the amino group. This is similar to acetic acid (pK\(_{a}\) ≈ 4.76) and ammonia (pK\(_{a}\) ≈ 9.25) as models.

3. Structure of glutamic acid and assigning pK\(_{a}\) values

Glutamic acid (also known as Glu or E) has the molecular formula C\(_{5}\)H\(_{9}\)NO\(_{4}\) and the following chemical structure: \[HOOC-CH(NH_2)-CH_2-CH_2-COOH\] Glutamic acid has three pK\(_{a}\) values: 2.10, 4.07, and 9.47. We can assign these pK\(_{a}\) values to the appropriate parts of the molecule: - 2.10 (first carboxyl group): This value corresponds to the ionization of the acidic carboxyl group (COOH) on the left side of the structure. - 4.07 (second carboxyl group): This value corresponds to the ionization of the acidic carboxyl group (COOH) in the side chain. - 9.47 (amino group): This value corresponds to the ionization of the basic amino group (NH\(_{2}\)) in the molecule.

4. Identifying the unknown amino acid from the titration curve

As the unknown amino acid is titrated with a strong base, we will observe different pK\(_{a}\) values in the titration curve, which indicate the ionization of the acidic groups. Amino acids with pK\(_{a}\) values similar to the points of inflection in the titration curve are possible candidates for the unknown amino acid. From the given information, we cannot determine the specific titration curve or points of inflection, so the identification of the unknown amino acid cannot be completed in the scope of this exercise. To identify the unknown amino acid, further information about the titration curve or pK\(_{a}\) values would be needed.

Key concepts

pH dependency

Amino acids can take on different ionic forms depending on the pH of their environment.
At low pH levels, the solution is acidic, and both the amino group and carboxyl group in the amino acid are likely to retain extra hydrogen ions.
Thus, the amino group becomes NH\(_3^+\), while the carboxyl group remains as COOH. It essentially means that the amino acid is in its zwitterionic form, where both the positive and negative charges are balanced.
As you increase the pH (making the environment more alkaline), the carboxyl group tends to lose a proton and form COO\(^-\), while the amino group remains protonated as NH\(_3^+\).
This transformation highlights the ability of amino acids to adapt their charges based on the pH level.
Understanding this concept is crucial for applications like protein purification, which depend heavily on these charge differences.
The general adaptability of amino acids across a pH spectrum plays a crucial role in biological systems and laboratory environments.

pKa values

pK\(_a\) values are critical in understanding the ionization of amino acids.
These values indicate the pH at which half of the molecules of a specific acidic or basic group in an amino acid are deprotonated. It is essential to remember that most amino acids have two pK\(_a\) values: one for the carboxyl group and one for the amino group.
The pK\(_a\) value of the carboxyl group typically ranges from 2 to 3, whereas the amino group generally has a pK\(_a\) between 9 and 10.
Taking serine as an example, its pK\(_a\) values are 2.19 and 9.21, aligning respectively with its carboxyl and amino groups. These values reflect how the groups ionize at different pH levels.
For other amino acids, such as glutamic acid, there could be an additional ionizable group, leading to another pK\(_a\) value. This extra pK\(_a\) value explains the unique ionization behavior of specific side chains found in some amino acids.
Overall, understanding pK\(_a\) values is critical in predicting the behavior of amino acids in different solutions and optimizing protein folding and function.

Protein structure analysis

Protein structure can vary significantly due to amino acids' ionization changes at different pH levels.
This variation impacts not only the protein's overall charge but also its folding and function.
Proteins often contain regions that must maintain certain charges to interact correctly with other molecules or to function properly.Hence, analyzing a protein requires understanding how its amino acids behave at various pH levels.
Each amino acid's pK\(_a\) values significantly influence the protein's secondary and tertiary structures by dictating the charge and solubility characteristics.
Techniques like titration curves can provide data on how pK\(_a\) values relate to specific points where proteins change shape or solubility, assisting in identifying amino acids and their possible impact on protein functionality.
This understanding is fundamental in fields such as drug development, where the precise interaction of a protein with various agents needs to be optimized. Through protein structure analysis, scientists can better modify and enhance protein-based applications, making it a critical aspect of biochemical research.