Amino Acids and Proteins

Structure of α-amino acids

The 20 standard α-amino acids share the formula H₂N-CHR-COOH, with the variable side chain R determining the identity. Glycine (R = H) is the only achiral amino acid; the other 19 are chiral, all naturally occurring as the L-enantiomer (S-configuration, except L-cysteine which is R because of the priority of S in -CH₂SH). Side chains classify amino acids as: nonpolar (Ala, Val, Leu, Ile, Met, Phe, Trp, Pro), polar uncharged (Ser, Thr, Cys, Tyr, Asn, Gln), positively charged at pH 7 (Lys, Arg, His), and negatively charged (Asp, Glu). The FSc Punjab Textbook Chemistry XII Chapter 16 catalogues these.

Zwitterions and isoelectric point

At physiological pH, an amino acid exists predominantly as a zwitterion: the carboxyl group is deprotonated (-COO⁻, pK_a1 ~ 2) and the amino group is protonated (-NH₃⁺, pK_a2 ~ 9-10). The isoelectric point pI is the pH at which the molecule has zero net charge: pI = (pK_a1 + pK_a2)/2 for neutral amino acids. For acidic amino acids (Asp, Glu) with a third pK_a on the side chain (~3-4), pI = (pK_a1 + pK_aR)/2; for basic ones (Lys, Arg), pI = (pK_aR + pK_a2)/2. Glycine has pI ≈ 6.0; aspartate ≈ 2.8; lysine ≈ 9.7. At pH = pI the molecule does not migrate in an electric field (basis of electrophoresis).

Peptide bond and the protein hierarchy

A peptide bond is an amide linkage formed by condensation of -COOH of one amino acid with -NH₂ of another, with loss of water. The C-N bond has partial double-bond character due to resonance with the carbonyl, making it planar and rigid (no rotation), while φ and ψ angles around the α-carbon are free. Four hierarchical levels: primary (sequence of amino acids), secondary (α-helix and β-pleated sheet, stabilised by H-bonds between backbone C=O and N-H groups), tertiary (3-D folding driven by side-chain interactions: H-bonds, ionic salt bridges, disulphide bridges between cysteines, hydrophobic interactions), and quaternary (assembly of multiple polypeptide subunits, e.g. haemoglobin's α₂β₂ tetramer).

Synthesis and reactions

Strecker synthesis: RCHO + NH₃ + HCN → RCH(NH₂)CN; hydrolysis gives racemic RCH(NH₂)COOH. Gabriel phthalimide synthesis: phthalimide-K⁺ + α-haloester → N-alkylphthalimide; hydrazinolysis releases the primary amine to give an amino acid after ester hydrolysis. Reactions of amino acids: ninhydrin test gives a deep purple Ruhemann's complex (yellow with proline because its nitrogen is secondary) — the standard detection reagent on TLC. With nitrous acid, primary amino acids release N₂ quantitatively (Van Slyke method). Esterification of -COOH and acylation of -NH₂ proceed normally.

Denaturation and biological roles

Denaturation disrupts secondary, tertiary, and quaternary structures (peptide bonds remain intact) by heat, extreme pH, urea, detergents, organic solvents, or heavy metals. Egg white turning solid on boiling and milk curdling on souring are everyday examples. Enzymes are protein catalysts; haemoglobin transports O₂; collagen is structural; antibodies are immune proteins; insulin (51 amino acids in two chains linked by disulphide bridges) regulates glucose. Lehninger Principles of Biochemistry Chapters 3-4 give the canonical biochemical perspective; FSc covers the MDCAT-relevant fraction.