Amino Acid pKa Values
pKa values determine the protonation state of amino acid side chains and backbone groups. Understanding these values is critical for predicting charge states, buffer behavior, and protein function.
What pKa Means for Amino Acids
The pKa value of a functional group describes the pH at which it is half protonated and half deprotonated. For amino acids, this applies to the alpha-carboxyl group, the alpha-amino group, and any ionizable side chain. When pH equals pKa, the group exists in equal concentrations of protonated and deprotonated forms.
Key pKa Values to Know
Here are approximate pKa values for common ionizable amino acids:
| Group | pKa |
|---|---|
| Alpha-carboxyl | 2.0 |
| Alpha-amino | 9.5 |
| Aspartate (D) side chain | 3.9 |
| Glutamate (E) side chain | 4.2 |
| Histidine (H) side chain | 6.0 |
| Cysteine (C) side chain | 8.3 |
| Tyrosine (Y) side chain | 10.1 |
| Lysine (K) side chain | 10.5 |
| Arginine (R) side chain | 12.5 |
Histidine is particularly important because its pKa falls near physiological pH. This makes it an effective proton donor and acceptor in enzyme active sites.
The Henderson-Hasselbalch Equation
The Henderson-Hasselbalch equation relates pH, pKa, and the ratio of deprotonated to protonated species:
pH = pKa + log([A-]/[HA])
When pH is one unit above pKa, roughly 90 percent of the group is deprotonated. When pH is one unit below, approximately 90 percent is protonated. This simple relationship lets you predict charge states at any pH.
Buffer Regions and Titration Curves
A buffer resists pH change when acid or base is added. Effective buffering occurs within plus or minus one pH unit of the pKa. On a titration curve, this corresponds to the flat region where pH changes slowly as titrant is added. The steep portions of the curve occur at equivalence points where the group is fully protonated or deprotonated.
Mnemonic: “CHEK-DAY”
For the ionizable side chains, remember their approximate pKa order with “CHEK-DAY”: Cysteine (8.3), Histidine (6.0), Glutamate (4.2), Lysine (10.5), Aspartate (3.9), Arginine (12.5), Tyrosine (10.1). Sort them and you get Asp (3.9), Glu (4.2), His (6.0), Cys (8.3), Tyr (10.1), Lys (10.5), Arg (12.5).
Practical Application
When designing a peptide for therapeutic use, consider the pKa of residues at the target site. A histidine at position 27 might be protonated in endosomes (pH 5) but neutral at the cell surface (pH 7.4). This pH-dependent charge can be exploited for selective drug release.