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Amino acids and acid–base chemistry

Structure, classification, pKa, the Henderson–Hasselbalch equation and isoelectric point.

Key concepts

Every standard amino acid has a central α-carbon bonded to four groups: an amino group, a carboxyl group, a hydrogen atom and a side chain (R group). The side chain is what makes each amino acid different. All standard amino acids except glycine are chiral, and proteins are built from the L forms.

Near physiological pH (about 7.4) the α-carboxyl group (pKa ≈ 2) has lost its proton (–COO⁻) and the α-amino group (pKa ≈ 9–10) has gained one (–NH₃⁺). A molecule carrying both charges with no net charge is a zwitterion.

Side chains fall into families: hydrophobic, polar, positively charged (Lys, Arg, His), negatively charged (Asp, Glu), plus glycine and proline with special structural roles. See the 20 amino acids reference.

Henderson–Hasselbalch

pH = pKa + log([A⁻] / [HA])

When pH equals the pKa, a group is half protonated. Each pH unit away from the pKa changes the ratio tenfold: one unit above the pKa, about 91% is deprotonated.

Isoelectric point

The pI is the pH at which the molecule has no net charge. For an amino acid with a non-ionizable side chain, it is the average of its two pKa values. For acidic amino acids, average the two lowest pKa values; for basic ones, the two highest. Explore this visually in the titration curve explorer.

Worked example

Common mistakes

• Averaging all three pKa values for an amino acid with an ionizable side chain.
• Forgetting that above its pKa a group is mostly deprotonated, not protonated.
• Assuming histidine is always positively charged. Its side-chain pKa is about 6, so at pH 7.4 it is mostly neutral.

Check yourself

Go deeper

• OpenStax Biology 2e: Proteins
• LibreTexts Biochemistry
• PubChem