Amino acids: structure, charge and pKa !

The 20 amino acids share one backbone and differ in their side chain; their charge changes with pH, which decides how a protein folds and migrates.

Updated 2026-11-01

Key facts

Each amino acid has an α carbon bonded to an amino group, a carboxyl group, a hydrogen and a side chain (R); in proteins they are all L-amino acids.
Typical pKa: α-carboxyl ≈ 2 and α-amino ≈ 9–10. At pH 7.4 nearly all exist as zwitterions (−COO⁻ and −NH₃⁺).
Ionisable side chains: Asp and Glu (≈ 4, acidic), His (≈ 6), Cys (≈ 8), Tyr (≈ 10), Lys (≈ 10.5) and Arg (≈ 12.5, basic).
Isoelectric point (pI): the pH at which net charge is zero; it is the mean of the two pKa values on either side of the neutral form (glycine ≈ 6).
Histidine is the only amino acid that buffers well at physiological pH (imidazole pKa ≈ 6).

Henderson–Hasselbalch equation: pH = pKa + log ([base]/[acid]). When pH equals pKa, half of the group is protonated.
Below its pKa a group is protonated (carboxyl neutral, amino positive); above it, deprotonated (carboxyl negative, amino neutral).
To find the pI of an amino acid with an acidic side chain (Asp, Glu), average the two lowest pKa values; with a basic side chain (Lys, Arg, His), the two highest.
Side-chain classes: non-polar (Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp), polar uncharged (Ser, Thr, Cys, Tyr, Asn, Gln), acidic (Asp, Glu) and basic (Lys, Arg, His).
Glycine is the only amino acid with no chiral carbon; proline has its amino group inside a ring and breaks α-helices.
Essential (must come from the diet): phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, leucine and lysine; arginine is conditionally essential during growth.
At pH 8.6 (electrophoresis) almost all plasma proteins carry a net negative charge and move towards the anode, faster the lower their pI.

Essential: “PVT TIM HaLL” (Phe, Val, Thr, Trp, Ile, Met, His, Leu, Lys).

Inborn errors of amino acid metabolism (phenylketonuria, maple syrup urine disease) are picked up by newborn screening.
Swapping a charged amino acid for an uncharged one changes a protein's pI: that is why HbS (Glu→Val) runs differently on electrophoresis.
The main buffer inside the red cell is the histidine residues of haemoglobin.

Think of the answer, then tap the question to see it.

What net charge does glycine carry at pH 7.4?

About zero: the carboxyl (pKa ≈ 2) is deprotonated and the amino group (pKa ≈ 9.6) protonated; it is a zwitterion with net charge ≈ 0.

Why does histidine buffer well at physiological pH?

Its imidazole has a pKa ≈ 6, close to 7.4, so it can take up or give off protons in that range.

How is the isoelectric point of glutamic acid calculated?

Average the two lowest pKa values (α-carboxyl and side-chain carboxyl), which flank the form with zero net charge: about 3.2.

Which is the only amino acid without a chiral carbon?

Glycine: its side chain is a hydrogen, so the α carbon carries two identical substituents.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Amino acids: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); What are proteins and what do they do?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); L-Histidine (CID 6274) (PubChem, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.