An amino acid contains acid-base groups whose protonation states depend on pH. In water near neutral pH, a simple amino acid is usually not best represented as neutral $\mathrm{H_2N-CH(R)-COOH}$. Instead, proton transfer produces a zwitterion, a species carrying both positive and negative formal charges:

$$\mathrm{H_3N^+-CH(R)-COO^-}.$$

The molecule can still have net charge zero because the charges cancel.

For an amino acid with no ionizable side chain, lowering the pH favors protonation:

$$\mathrm{H_3N^+-CH(R)-COOH}$$

has net charge $+1$.

Raising the pH favors deprotonation:

$$\mathrm{H_2N-CH(R)-COO^-}$$

has net charge $-1$.

Between these extremes, the zwitterionic form is usually dominant.

Using $pK_a$ to predict charge

Each ionizable group has an acid dissociation constant. As a practical rule:

• when $\mathrm{pH}<pK_a$, the more protonated form is favored;
• when $\mathrm{pH}>pK_a$, the more deprotonated form is favored.

Consider glycine, whose carboxyl group has a much lower $pK_a$ than its ammonium group. As pH rises, the carboxyl group loses its proton first, changing the net charge from $+1$ to $0$. At still higher pH, the ammonium group loses a proton and the net charge becomes $-1$.

Amino acids with acidic or basic side chains have additional protonation transitions, so their net charge must include the side chain as well as the α-amino and α-carboxyl groups.

Isoelectric point

The isoelectric point, $pI$, is the pH at which the average net charge of a molecule is zero. For an amino acid with only the two backbone ionizations, the neutral zwitterion lies between the two relevant $pK_a$ values, so

$$\boxed{pI\approx\frac{pK_{a,1}+pK_{a,2}}{2}}.$$

This averaging rule must use the two $pK_a$ values that surround the net-zero form; amino acids with ionizable side chains may require a different pair.

The $pI$ does not mean that every molecule has no formal charges. At the isoelectric point, zwitterionic charged groups can still be present even though the net charge averages to zero.

Because charge changes with pH, amino-acid and protein solubility, electrostatic interactions, migration in an electric field and catalytic behavior can all depend strongly on the surrounding acid-base conditions.