Amino Acids and Proteins

The Twenty Amino Acids

Classify side chains: nonpolar (Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, Trp), polar uncharged (Ser, Thr, Cys, Tyr, Asn, Gln), acidic (Asp, Glu), and basic (Lys, Arg, His). Know the special cases — glycine is achiral, proline kinks helices, cysteine forms disulfides, and histidine's $pK_a$ near 6 makes it the physiological proton shuttle. Chiral amino acids appear as L-isomers in proteins.

Ionization and Isoelectric Point

At physiological pH, amino acids are zwitterions: carboxylate negative, ammonium positive. A group is protonated when pH is below its $pK_a$. The isoelectric point averages the two $pK_a$ values flanking the neutral species: $pI = \frac{pK_{a1} + pK_{a2}}{2}$ Acidic residues have low pI, basic residues high; charge at a given pH predicts electrophoretic behavior.

Protein Structure

Primary structure is the peptide-bonded sequence; secondary structure (alpha-helices, beta-sheets) is backbone hydrogen bonding; tertiary structure folds via side-chain interactions — hydrophobic packing, hydrogen bonds, salt bridges, disulfide bonds; quaternary structure assembles multiple subunits (hemoglobin). Denaturation destroys folding but not peptide bonds.

Key Takeaways

• Side-chain classification predicts folding location: hydrophobic in, hydrophilic out.
• pH below $pK_a$ means protonated; count charges to find pI behavior.
• Secondary structure is backbone-only; tertiary is side-chain driven.
• Histidine buffers near pH 7 — the exam's favorite residue.