list the amino acids that will carry a net charge at pH 7 within a protein. What is the charge at pH 7 for each of the amino acids you have listed (-2, -1, +1, etc.)? What is the net charge at pH 7 of the tetrapeptide shown in figure 4.17?
The Correct Answer and Explanation is:
At pH 7, only the amino acids with ionizable side chains will carry a net charge. These are the amino acids whose side chains can donate or accept protons around physiological pH.
Amino Acids with Net Charge at pH 7
| Amino Acid | Side Chain Group | Charge at pH 7 |
|---|---|---|
| Aspartate (Asp, D) | Carboxyl (-COO⁻) | -1 |
| Glutamate (Glu, E) | Carboxyl (-COO⁻) | -1 |
| Lysine (Lys, K) | Amino (-NH₃⁺) | +1 |
| Arginine (Arg, R) | Guanidinium | +1 |
| Histidine (His, H) | Imidazole | ~0.1 to +1* |
| Tyrosine (Tyr, Y) | Phenol | 0 |
| Cysteine (Cys, C) | Thiol (-SH) | 0 |
*Histidine has a pKa ~6.0, so at pH 7, it’s partially protonated — roughly 10% of histidine side chains are positively charged.
Net Charges Summary
- Aspartate (Asp): -1
- Glutamate (Glu): -1
- Lysine (Lys): +1
- Arginine (Arg): +1
- Histidine (His): +0.1 (partially positive)
- Tyrosine and Cysteine are largely neutral at pH 7
Net Charge of Tetrapeptide in Figure 4.17
Since you mentioned Figure 4.17 without providing it, I will reference the commonly used Figure 4.17 from Lehninger’s Principles of Biochemistry, which shows the tetrapeptide Ala-Glu-Ala-Lys.
- Alanine (Ala): no charged side chain → 0
- Glutamate (Glu): charged side chain → -1
- Lysine (Lys): charged side chain → +1
- N-terminus (Ala): free amino group → +1
- C-terminus (Lys): free carboxyl group → -1
Total Net Charge at pH 7 for Ala-Glu-Ala-Lys
(+1 N-term)+(0)+(−1 Glu)+(0)+(+1 Lys)+(−1 C-term)=0(+1\ \text{N-term}) + (0) + (-1\ \text{Glu}) + (0) + (+1\ \text{Lys}) + (-1\ \text{C-term}) = \boxed{0}
At physiological pH (~7.0), amino acids behave differently depending on the ionizability of their side chains. Each amino acid has a backbone amino and carboxyl group, but only a few have side chains that can gain or lose protons near this pH. These ionizable side chains influence the molecule’s overall charge, affecting protein structure, interaction, and function.
Negatively charged side chains at pH 7 include those of aspartate and glutamate, as their carboxyl side groups lose protons (deprotonated). They contribute a charge of -1 each. Positively charged side chains include lysine, arginine, and sometimes histidine. Lysine and arginine are fully protonated and thus contribute +1 each. Histidine, with a side chain pKa near 6.0, is partly protonated at pH 7, and typically about 10% of histidines are positively charged.
In the peptide Ala-Glu-Ala-Lys, alanine has no ionizable side chain, so it is neutral. Glutamate contributes a -1 charge from its side chain, and lysine contributes a +1. The termini also contribute: the N-terminal amine is positively charged (+1), while the C-terminal carboxyl is negatively charged (-1). When summed, these charges cancel out to yield a net charge of 0 at pH 7.
Understanding amino acid charges is crucial for predicting peptide solubility, isoelectric point, and interactions with other biomolecules. It also plays a role in techniques such as electrophoresis, protein purification, and enzyme mechanism studies.
