Problem 91 - Chemistry The Central Science

Question

Which of the following peptides have a net positive charge at \(\mathrm{pH} 7 ?\) (a) Gly-Ser-Lys, (b) Pro-Leu-lle, (c) Phe-Tyr-Asp.

Step-by-Step Solution

Answer

Out of the given peptides, only peptide (a) Gly-Ser-Lys has a net positive charge at pH 7.

Step 1: Peptide (a): Gly-Ser-Lys

1. Identify the amino acids and their classification: - Gly (Glycine): Neutral - Ser (Serine): Neutral - Lys (Lysine): Basic 2. Determine the charges at pH 7: - N-terminal: Positive charge - Gly (Glycine): No charge - Ser (Serine): No charge - Lys (Lysine): Positive charge (because pH 7 is below its pKa ~ 10.5) - C-terminal: Negative charge 3. Calculate the net charge: Net charge = Positive charges - Negative charges = (1 + 1) - 1 = +1

Step 2: Peptide (b): Pro-Leu-Ile

1. Identify the amino acids and their classification: - Pro (Proline): Neutral - Leu (Leucine): Neutral - Ile (Isoleucine): Neutral 2. Determine the charges at pH 7: - N-terminal: Positive charge - Pro (Proline): No charge - Leu (Leucine): No charge - Ile (Isoleucine): No charge - C-terminal: Negative charge 3. Calculate the net charge: Net charge = Positive charges - Negative charges = 1 - 1 = 0

Step 3: Peptide (c): Phe-Tyr-Asp

1. Identify the amino acids and their classification: - Phe (Phenylalanine): Neutral - Tyr (Tyrosine): Acidic - Asp (Aspartic acid): Acidic 2. Determine the charges at pH 7: - N-terminal: Positive charge - Phe (Phenylalanine): No charge - Tyr (Tyrosine): No charge (because pH 7 is above its pKa ~ 5.74) - Asp (Aspartic acid): Negative charge (because pH 7 is above its pKa ~ 4) - C-terminal: Negative charge 3. Calculate the net charge: Net charge = Positive charges - Negative charges = 1 - (1+1) = -1 Out of the given peptides, only peptide (a) Gly-Ser-Lys has a net positive charge at pH 7.

Key Concepts

Peptide Net Charge Calculation

Determining the net charge of a peptide at a specific pH is crucial when studying protein function and structure. Let's break this process down into comprehensible steps making it easier for you to grasp the concept. First, consider the pH at which you are examining the peptide. For pH 7, a common physiological condition, you'll need to know the charge of each amino acid within the peptide at this pH.
To calculate the net charge, remember to account for the amino and carboxyl termini, which respectively carry a positive and negative charge under physiological conditions. Next, tally the charges of all the amino acids and balance them against the charges contributed by the termini. A basic guideline is:

• Basic amino acids (lysine, arginine, and histidine) typically carry a positive charge at pH 7.
• Acidic amino acids (aspartic acid and glutamic acid) carry a negative charge.
• Neutral amino acids do not contribute to the overall charge under neutral conditions.

The net charge is then the sum of all positive and negative charges. Considering our exercise, peptide (a) Gly-Ser-Lys, with glycine and serine being neutral and lysine being basic, the net charge comes out to be +1, indicating a net positive charge at pH 7.

Amino Acid Classification

For successful peptide net charge calculation, we must understand the classification of amino acids. Generally, amino acids are categorized based on the properties of their side chains into three main groups:

• Acidic amino acids (e.g., aspartic acid, glutamic acid) and their amides.
• Basic amino acids (e.g., lysine, arginine, histidine).
• Neutral amino acids which are further subdivided into polar (e.g., serine, threonine) and nonpolar (e.g., leucine, isoleucine).

Acidic and basic amino acids can be charged depending on the pH of the environment, while neutral ones generally remain uncharged. This classification scheme is essential for predicting how a peptide will behave in different environments, like the net positive charge of peptide (a) containing a basic amino acid, lysine, at pH 7.

pKa and Amino Acid Charge Relationship

The pKa value of an amino acid is a measure of its acid dissociation tendency—the lower the pKa, the stronger the acid. This value is pivotal because it helps us determine the charge state of an acidic or basic amino acid at a given pH. If the pH is lower than the pKa, the amino acid is likely to be in its protonated form, and vice versa.
For instance, in peptide (c), aspartic acid has a pKa around 4, so at pH 7, it will be deprotonated and negatively charged. Tyrosine, however, with a pKa around 5.74, will also be deprotonated but in the specific case of pH 7, it generally does not carry a charge due to the phenolic group's weak acidity. Understanding the relationship between pKa and pH is essential for determining the charge of amino acids and, by extension, peptides in different environments. It's this relationship that justifies why peptide (a) Gly-Ser-Lys carries a net positive charge and peptide (c) Phe-Tyr-Asp carries a net negative charge at pH 7.