Amino Acids and Peptides: Structure, Properties, and Biochemical Roles

5.1 Amino Acids

The Structure of an α-Amino Acid

Amino acids are the fundamental building blocks of proteins, each containing a central α-carbon atom bonded to four distinct groups: an amino group, a carboxylic acid group, a hydrogen atom, and a unique side chain (R group). The α-carbon is typically an asymmetric center, making most amino acids chiral.

• α-Carbon: Central atom in amino acids, attached to amino, carboxyl, hydrogen, and R group.

• Chirality: When the R group is not hydrogen, the α-carbon is a stereocenter.

• Zwitterion: At neutral pH, the amino group is protonated and the carboxylic acid group is deprotonated, resulting in a molecule with both positive and negative charges.

• Example: Glycine is the only non-chiral amino acid because its R group is hydrogen.

α-Amino Acid Stereochemistry

The stereochemistry of amino acids is crucial for protein structure and function. Most amino acids exist as enantiomers, with the L-form being predominant in biological systems.

• Chiral Center: Four different groups attached to the α-carbon make it chiral.

• Enantiomers: L-alanine and D-alanine are mirror images (enantiomers).

• Fischer Projection: A 2D representation used to depict stereochemistry.

• Example: All 20 common amino acids except glycine are chiral.

Classification of Naturally Occurring Amino Acids

The 20 standard amino acids are classified based on the properties of their side chains, which influence protein structure and function.

• Nonpolar Aliphatic: Glycine, Alanine, Valine, Leucine, Isoleucine

• Nonpolar Aromatic: Phenylalanine, Tyrosine, Tryptophan

• Polar Uncharged: Serine, Threonine, Asparagine, Glutamine

• Positively Charged (Basic): Histidine, Lysine, Arginine

• Negatively Charged (Acidic): Aspartic acid, Glutamic acid

General Properties of Amino Acids

Amino acids exhibit unique chemical properties, including UV absorbance and ionization behavior, which are important for protein analysis and function.

• UV Absorption: Tyrosine and tryptophan absorb UV light at 280 nm, allowing protein quantification; nucleic acids absorb most strongly at 260 nm.

• Ionizable Groups: Amino acids have groups with characteristic pKa values, affecting their charge at different pH levels.

Group Type	Typical pKa Range
α-Carboxyl	3.5–4.0
Side-chain carboxyl (Asp, Glu)	4.0–4.8
Imidazole (His)	6.5–7.4
Cysteine (–SH)	8.0–9.0
Phenolic (Tyr)	9.5–10.5
α-Amino	8.0–9.0
Side-chain amino (Lys)	9.8–10.4
Guanidinium (Arg)	>12

Titration Curve of Histidine

The titration curve of histidine illustrates how its charge changes with pH, with distinct pKa values for its ionizable groups.

• Charge Variation: Histidine's charge ranges from +2 to –1 depending on pH.

• pI (Isoelectric Point): The pH at which the net charge is zero.

Posttranslational Modification of Amino Acids

Posttranslational modifications alter amino acids after protein synthesis, affecting protein function, stability, and signaling.

• Functions: Signaling pathways, calcium binding, stabilizing structures (e.g., collagen), gene expression/suppression.

• Examples: Phosphoserine, 4-hydroxyproline, N-acetyllysine, γ-carboxyglutamate.

5.2 Peptides and the Peptide Bond

Peptide Bond Formation between Amino Acids

Peptide bonds link amino acids in proteins through a condensation reaction, releasing water. This process is energetically unfavorable and requires coupling to ATP hydrolysis during biosynthesis.

• Condensation Reaction: Two amino acids join, forming a peptide bond and releasing H2O.

• Energetics: Not thermodynamically favorable; coupled to ATP hydrolysis.

• Equation: $ext{Amino acid}_1 + ext{Amino acid}_2 ightarrow ext{Dipeptide} + H_2O$

Structure of the Peptide Bond

The peptide bond is characterized by electron delocalization, resulting in a planar and stable structure that restricts rotation and influences protein folding.

• Planarity: Peptide bonds are planar due to resonance between the carbonyl and amide nitrogen.

• Stability: Delocalization of electrons stabilizes the bond.

Peptide Bond Cleavage

Peptide bonds can be hydrolyzed by strong acid, high temperature, or specific enzymes called proteases. The free energy change for hydrolysis is approximately –10 kJ/mol.

• Stability: Peptides are stable unless exposed to strong acid or a catalyst.

• Proteases: Enzymes that cleave specific peptide bonds.

• Equation: $ext{Peptide} + H_2O ightarrow ext{Amino acids}$

Sequence Specificities for Proteases

Enzyme	Preferred Site	Source
Trypsin	R, K	Digestive systems of animals
Chymotrypsin	F, Y, W	Digestive systems of animals
Thrombin	R	Blood, clotting cascade
V-8 protease	E	Staphylococcus aureus
Cyanogen bromide	M	Chemical reagent
Additional info: Other proteases have unique specificities for different amino acid sequences.

Oligopeptides

Peptides are short chains of amino acids. Oligopeptides typically contain 3–15 residues, while polypeptides have more than 15 residues.

• Oligopeptides: Short peptide chains (3–15 amino acids).

• Polypeptides: Longer chains (>15 amino acids).

Important Peptide Regions

Peptides have distinct regions, including the amino (N-) terminus, carboxy (C-) terminus, main chain, and side chains, which are critical for protein structure and function.

• N-terminus: Free amino group at one end.

• C-terminus: Free carboxyl group at the other end.

• Main chain: Backbone of the peptide.

• Side chains: R groups projecting from the main chain.

Common Modifications of Amino- and Carboxy-Termini in Peptides

Peptide termini can be chemically modified, affecting protein stability and function.

• N-formyl group: Blocks the N-terminus.

• N-acetyl group: Blocks the N-terminus.

• C-terminal amide: Blocks the C-terminus.

Peptides and Proteins as Polyampholytes

Peptides and proteins contain multiple ionizable groups, making them polyampholytes. Their net charge varies with pH, influencing solubility and interactions.

• Charge Behavior: As pH increases, the overall charge becomes more negative; as pH decreases, it becomes more positive.

• Isoelectric Point (pI): The pH at which the net charge is zero.

Additional info: Understanding the ionization behavior of peptides is essential for techniques such as isoelectric focusing and protein purification.