Rucete ✏ Lehninger Principles of Biochemistry In a Nutshell
3.1 Amino Acids
This chapter introduces the fundamental properties, classification, and chemical behavior of the 20 amino acids that serve as building blocks for proteins.
Basic Structure and Nomenclature
• Proteins are polymers of amino acids, linked by covalent peptide bonds.
• Each amino acid has a central (α) carbon bonded to an amino group, a carboxyl group, a hydrogen atom, and a variable side chain (R group).
• All amino acids except glycine have a chiral α-carbon, allowing two stereoisomers (L and D); proteins use almost exclusively the L-forms.
• Amino acids are abbreviated using both three-letter and one-letter codes for convenience in sequence representation.
Classification of Amino Acids
• Amino acids are grouped based on the polarity and charge of their R groups, especially at pH 7.0 (biological pH).
• Five main classes: nonpolar aliphatic, aromatic, polar uncharged, positively charged (basic), and negatively charged (acidic) R groups.
• Examples: Glycine (nonpolar, small), phenylalanine/tyrosine/tryptophan (aromatic), serine/threonine (polar, uncharged), lysine/arginine/histidine (positively charged), aspartate/glutamate (negatively charged).
Chemical Properties and Ionization
• Amino acids can act as both acids and bases due to their amino and carboxyl groups (ampholytes).
• At neutral pH, most amino acids exist as zwitterions, carrying both a positive and negative charge.
• Acid-base titration curves show distinct buffering regions and inflection points for each ionizable group; the isoelectric point (pI) is the pH where net charge is zero.
• Amino acids with ionizable R groups (e.g., lysine, glutamate, histidine) have more complex titration curves and additional buffering zones.
Stereochemistry and Biochemical Relevance
• Only L-amino acids are incorporated into proteins, allowing uniform secondary and tertiary structures.
• Enzyme specificity for L-forms is due to the asymmetric nature of active sites.
• D-amino acids occur rarely, often through post-translational modification for specific biological functions.
Uncommon and Modified Amino Acids
• Some amino acids in proteins arise from modification after synthesis (e.g., hydroxyproline in collagen, γ-carboxyglutamate in clotting factors).
• Selenocysteine and pyrrolysine are rare amino acids directly incorporated during translation in specific organisms.
• Other non-protein amino acids like ornithine and citrulline serve as metabolic intermediates.
• Post-translational modifications (phosphorylation, methylation, etc.) regulate protein activity and function.
Physical and Chemical Functions of R Groups
• Nonpolar R groups contribute to hydrophobic core formation in proteins, stabilizing structure.
• Aromatic amino acids absorb UV light (notably tryptophan and tyrosine at 280 nm), useful for protein quantification.
• Polar and charged R groups interact with water, form hydrogen bonds, and participate in catalysis and binding.
• Disulfide bonds between cysteine residues stabilize protein structure.
• Histidine’s imidazole side chain provides buffering capacity near neutral pH and is important in enzyme mechanisms.
In a Nutshell
• The 20 standard amino acids share a common core structure but differ in their R groups, dictating protein diversity and function.
• Their acid-base properties, stereochemistry, and side chain characteristics underlie all of protein chemistry, folding, and enzymatic activity.
• Classification by R group properties enables prediction of protein behavior in different environments.
• Knowledge of amino acid chemistry is essential for understanding all aspects of biochemistry and molecular biology.