Introduction to Charged Amino Acids
Amino acids are the fundamental building blocks of proteins. All amino acids contain a central alpha carbon attached to an amino group and a carboxyl group, but the unique side chain (R-group) determines specific characteristics. At physiological pH (around 7.4), the amino group is typically protonated ($–NH_3^+$) and the carboxyl group is deprotonated ($–COO^–$), resulting in a zwitterion with a net zero charge for most amino acids. However, five amino acids have ionizable side chains that carry a net positive or negative charge at this pH, influencing protein properties.
The Positively Charged (Basic) Amino Acids
Three amino acids are basic with positively charged side chains at physiological pH due to high pKa values causing them to accept a proton ($H^+$).
Arginine (Arg, R)
Arginine has a highly basic guanidinium group with a pKa of approximately 12.5, remaining protonated and positively charged at physiological pH. This positive charge facilitates strong ionic and hydrogen bonds, often interacting with negative molecules or other amino acids on the protein's exterior.
Lysine (Lys, K)
Lysine's side chain ends with a primary amino group ($–NH_3^+$) with a pKa around 10.5, which is protonated and positively charged at physiological pH. This positive charge makes lysine hydrophilic and important for electrostatic interactions, often found on protein surfaces.
Histidine (His, H)
Histidine is unique with an imidazole ring side chain having a pKa near 6.0. Its pKa being close to physiological pH allows it to be both protonated (positive) and deprotonated (neutral) in the cell. This property makes histidine crucial in enzyme active sites as a proton donor or acceptor, where small pH changes can alter its charge and the protein's function.
The Negatively Charged (Acidic) Amino Acids
Two amino acids are acidic with negatively charged side chains at physiological pH, due to low pKa values causing them to donate a proton.
Aspartic Acid (Asp, D)
Aspartic acid has a beta-carboxyl group side chain with a pKa around 3.9. This low pKa relative to physiological pH means it exists primarily as the deprotonated, negatively charged aspartate ($–COO^–$). Its negative charge and hydrophilicity typically place it on the solvent-exposed surface of proteins.
Glutamic Acid (Glu, E)
Glutamic acid is similar to aspartic acid but with an extra methylene group leading to a gamma-carboxyl group. Its pKa is about 4.2, resulting in a deprotonated, negatively charged glutamate ($–COO^–$) at physiological pH. Glutamic acid also functions as a neurotransmitter and in metabolism.
The Role of pH and pKa
The charge of an amino acid's ionizable group is determined by its pKa and the surrounding pH. For basic side chains, if pH < pKa, the group is protonated (positive). Arginine (pKa~12.5) and lysine (pKa~10.5) are positive at pH 7.4. For acidic side chains, if pH > pKa, the group is deprotonated (negative). Aspartic acid (pKa~3.9) and glutamic acid (pKa~4.2) are negative at pH 7.4. Histidine (pKa~6.0) is near physiological pH, making it sensitive to small pH changes and useful as a buffer.
Comparison of Charged Amino Acids
| Feature | Positively Charged (Basic) Amino Acids | Negatively Charged (Acidic) Amino Acids |
|---|---|---|
| Members | Arginine (Arg, R), Lysine (Lys, K), Histidine (His, H) | Aspartic Acid (Asp, D), Glutamic Acid (Glu, E) |
| Side Chain | Arginine has a guanidinium group. Lysine has a primary amino group. Histidine has an imidazole ring. | Both have a carboxylic acid group in their side chain. |
| Charge at pH 7.4 | +1 (Histidine is special, see above) | -1 |
| pKa of Side Chain | Arginine: ~12.5; Lysine: ~10.5; Histidine: ~6.0 | Aspartic Acid: ~3.9; Glutamic Acid: ~4.2 |
| Role in Proteins | Participate in electrostatic interactions and binding with negatively charged molecules (e.g., DNA). | Crucial for forming ionic bonds and interacting with positively charged metal ions. |
| Key Functions | Histidine is a proton donor/acceptor in enzyme catalysis. | Glutamic acid and aspartic acid are neurotransmitters and aid in metabolism. |
| Location | Often found on the protein surface due to hydrophilic nature. | Often found on the protein surface due to hydrophilic nature. |
Conclusion
The five charged amino acids—arginine, lysine, histidine, aspartic acid, and glutamic acid—are essential for protein structure, stability, and function. Their charged side chains at physiological pH enable electrostatic interactions like salt bridge formation, substrate binding, and enzyme catalysis. Differences in pKa, especially for histidine, expand protein functional diversity. Understanding these charged residues is fundamental to biochemistry and molecular biology.
For additional information on the properties of amino acids, consult authoritative resources such as the NCBI Bookshelf, which features in-depth articles on biochemistry and cell biology.
The List of Charged Amino Acids
- Positively Charged (Basic):
- Arginine (Arg, R)
- Lysine (Lys, K)
- Histidine (His, H)
- Negatively Charged (Acidic):
- Aspartic Acid (Asp, D)
- Glutamic Acid (Glu, E)
The Uncharged Polar Amino Acids
For a complete picture, it is also useful to remember the polar, but uncharged, amino acids:
- Serine (Ser, S)
- Threonine (Thr, T)
- Tyrosine (Tyr, Y)
- Asparagine (Asn, N)
- Glutamine (Gln, Q)
- Cysteine (Cys, C)
The Nonpolar Amino Acids
Finally, the nonpolar amino acids, which are typically neutral and hydrophobic:
- Alanine (Ala, A)
- Valine (Val, V)
- Leucine (Leu, L)
- Isoleucine (Ile, I)
- Proline (Pro, P)
- Methionine (Met, M)
- Phenylalanine (Phe, F)
- Tryptophan (Trp, W)
- Glycine (Gly, G)
This categorization based on the side chain properties highlights the chemical diversity that defines amino acid function and, by extension, protein structure and activity.
