Biochemistry - Lesson 2: Amino Acids and Peptides
Amino acids are the foundational building blocks of proteins, and understanding their diverse properties is vital for appreciating how proteins function in living systems. This expanded lesson delves deeper into amino acid structures, ionization behaviors, and peptide bond formation. It also illustrates how amino acid side chains contribute to chemical reactivity, folding, and the encoding of higher-level protein structures.
Overview of Amino Acids
Each amino acid features an α-amino group (–NH2), an α-carboxyl group (–COOH), a hydrogen atom, and a distinct side chain (R-group) attached to a central α-carbon. The R-group determines its chemical behavior, which in turn influences protein folding and function. Of the 20 standard amino acids:
- Nonpolar (Hydrophobic): e.g., Leucine, Valine, Isoleucine, which cluster away from water in protein cores.
- Polar (Uncharged): e.g., Serine, Threonine, Asparagine, capable of hydrogen bonding with water or other polar residues.
- Acidic (Negatively Charged): Aspartate, Glutamate, typically deprotonated at physiological pH.
- Basic (Positively Charged): Lysine, Arginine, Histidine, can accept protons near physiological pH.
The α-carbon of most amino acids is chiral, giving rise to stereoisomers, but L-amino acids dominate in nature. Glycine is the only non-chiral amino acid, as its R-group is simply a hydrogen.
Ionization and Zwitterionic Nature
In aqueous solutions, amino acids can act as both acids and bases (amphoteric). At physiological pH (~7.4), most amino acids adopt a zwitterion form with a negatively charged carboxylate group (–COO−) and a positively charged amino group (–NH3+). Side chains with acidic or basic groups further complicate ionization behavior. Ionization constants (pKa) for the α-carboxyl, α-amino, and side chain groups determine the net charge at any given pH.
Titration Curves and Isoelectric Point (pI)
A titration curve for an amino acid charts its net charge as pH changes. When the net charge is zero, the amino acid is at its isoelectric point (pI). The pI is approximately the average of relevant pKa values:
pI = (pKa1 + pKa2)/2
(for amino acids without ionizable side chains)
For example, glycine has two relevant pKa values (~2.3 for the carboxyl group, ~9.6 for the amino group). Its pI is roughly (2.3 + 9.6)/2 ≈ 5.95. Amino acids with ionizable side chains (e.g., Asp, Glu, Lys, Arg) use an average of the pKa values that define the neutral species.
The chart above is a simplified titration curve showing how an amino acid's net charge shifts with rising pH. The horizontal line at net charge = 0 denotes the approximate point where the molecule is neutral overall (isoelectric point).
Peptide Bond Formation and Characteristics
A peptide bond forms via a condensation reaction between the α-carboxyl group of one amino acid and the α-amino group of another, releasing water. This bond has partial double-bond character due to resonance between the carbonyl and the amide nitrogen, restricting rotation around the C–N axis. Key points include:
- The backbone comprises repeated –N–Cα–C– units.
- The planarity of the peptide bond impacts secondary structure formation (e.g., α-helices, β-sheets).
- Prolonged chains of amino acids are referred to as polypeptides; one or more polypeptides can form a functional protein.
Higher-Level Protein Structure Encoding
The primary structure, or the amino acid sequence, inherently encodes how a protein will fold into its secondary, tertiary, and sometimes quaternary structures. Changes in even a single amino acid can dramatically alter protein conformation and function, exemplified by diseases such as sickle cell anemia (a mutation in the β-chain of hemoglobin).
Side chains influence intermolecular forces:
- Hydrophobic interactions (nonpolar residues)
- Hydrogen bonds (polar groups, amide backbone, side chains)
- Electrostatic interactions (charged side chains)
- Disulfide bridges (Cysteine residues forming S–S bonds)
These interactions stabilize the protein’s native conformation, critical for biological activity.
Functional Implications
Amino acid properties underpin enzyme active sites, binding domains, and regulatory motifs in proteins. Basic residues (Lys, Arg) may facilitate binding to negatively charged DNA or substrates, while acidic residues (Asp, Glu) can participate in catalysis or metal coordination. Aromatic residues (Phe, Tyr, Trp) often contribute to hydrophobic cores and can absorb UV light (especially Trp at ~280 nm), aiding protein quantification in research.
Modifications to amino acids (e.g., phosphorylation of Ser, Thr, Tyr) regulate protein activity, localization, and signal transduction. Therefore, even subtle variations in amino acid composition can have profound effects on protein function and cellular processes.
Summary
This expanded examination of amino acids emphasizes their structural variety, ionization behavior, and how these factors shape peptide bond formation and higher-level protein configurations. Mastery of amino acid chemistry is essential for understanding enzyme mechanisms, metabolic pathways, and virtually all aspects of molecular biology.
Suggested Reading:
Lehninger Principles of Biochemistry (chapters on amino acid chemistry and peptide bonds)
Biochemistry by Berg, Tymoczko, and Stryer (sections detailing amino acid side chain reactivity, stereochemistry,
and protein structure encoding)
