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

5.1 Amino Acids

Structure of an α-Amino Acid

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

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

• Chirality: When the α-carbon has four different groups, it is chiral (asymmetric center).

• 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 a hydrogen atom.

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: The α-carbon is chiral in all amino acids except glycine.

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

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

• Example: L-amino acids are incorporated into proteins, while D-amino acids are rare in nature.

Classification of Naturally Occurring Amino Acids

The 20 common amino acids found in proteins are classified based on the properties of their side chains: nonpolar aliphatic, nonpolar aromatic, polar uncharged, positively charged, and negatively charged.

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

• Nonpolar Aromatic: Phenylalanine, Tyrosine, Tryptophan

• Polar Uncharged: Serine, Threonine, Asparagine, Glutamine

• Positively Charged: Lysine, Arginine, Histidine

• Negatively Charged: Aspartic acid, Glutamic acid

• Example: Tyrosine and tryptophan are aromatic amino acids with significant UV absorbance.

General Properties of Amino Acids

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

• UV Absorption: Tyrosine and tryptophan absorb UV light at 280 nm, allowing protein quantification; nucleic acids absorb 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: The charge on amino acids like histidine changes with pH; the isoelectric point (pI) is where net charge is zero.

• Posttranslational Modifications: Amino acids can be chemically modified after translation, affecting signaling, calcium binding, structural stability, and gene expression.

• Example: Phosphorylation of serine (phosphoserine) is a common regulatory modification.

5.2 Peptides and the Peptide Bond

Peptide Bond Formation between Amino Acids

Peptide bonds link amino acids together to form peptides and proteins. This condensation reaction releases water and is energetically coupled to ATP hydrolysis during biosynthesis.

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

• Energetics: The reaction is not thermodynamically favorable and requires energy input from 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 contributes to protein secondary structure.

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

• Stability: The bond is stable under physiological conditions.

• Example: The partial double-bond character of the peptide bond limits rotation, influencing protein folding.

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 about –10 kJ/mol.

• Hydrolysis: Peptides are stable unless exposed to strong acid (e.g., 6N HCl, 12–24 h) or a catalyst.

• Proteases: Enzymes that cleave peptide bonds at specific sequences.

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

Sequence Specificities for Proteases

Enzyme	Preferred Site	Source
Trypsin	R, K (Arg, Lys)	Digestive system of animals
Chymotrypsin	F, Y, W, L (Phe, Tyr, Trp, Leu)	Digestive system of animals
Thrombin	R (Arg)	Blood, clotting cascade
V-8 protease	E (Glu)	Staphylococcus aureus
Cyanogen bromide	M (Met)	Chemical reagent

Oligopeptides

Peptides are short chains of amino acids. Oligopeptides 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).

• Example: Glutathione is a tripeptide with antioxidant properties.

Important Peptide Regions

Peptides and proteins have distinct regions, including the amino (N-) terminus, carboxy (C-) terminus, main chain, and side chains, which determine their structure and function.

• N-terminus: The end with a free amino group.

• C-terminus: The end with a free carboxyl group.

• Main Chain: The repeating backbone of the peptide.

• Side Chains: The variable R groups that confer unique properties.

Common Modifications of Amino- and Carboxy-Termini in Peptides

Peptide termini can be chemically modified to alter protein stability, localization, or function.

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

• N-acetyl group: Acetylation of the N-terminus.

• C-terminal amide: Amidation of the C-terminus.

• Example: N-terminal acetylation is common in eukaryotic proteins and affects protein lifespan.

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.

• Example: The titration curve of a tetrapeptide shows stepwise changes in charge as pH changes.

Additional info: Understanding amino acid and peptide chemistry is foundational for studying protein structure, enzyme function, and metabolic pathways in biochemistry.