describe and draw the general structure of an amino acid and the formation and breakage of a peptide bond

Proteins – A‑Level Biology (9700)

Learning Objective

Describe and draw the general structure of an α‑amino acid, explain how peptide bonds are formed and broken (including the energetic aspects), and relate protein structure to function and disease.

1. General Structure of an α‑Amino Acid

• α‑Carbon (Cα) – a chiral centre in all amino acids except glycine (where the side‑chain R = H).
• Four groups attached to Cα:

  • Amino group – –NH₂ (neutral) or –NH₃⁺ at physiological pH (~7.4).
  • Carboxyl group – –COOH (neutral) or –COO⁻ at physiological pH.
  • Hydrogen atom – –H.
  • Side chain (R) – varies between the 20 standard amino acids and determines chemical properties.

• Quick tip: A carbon is chiral when it is attached to four different substituents; indicate stereochemistry with a wedge‑dash pair.

2. Peptide‑Bond Formation (Condensation)

2.1 Overall Reaction

\[

\mathrm{R1CH(NH3^+)COO^- \;+\; H3N^+CH(R2)COO^-

\;\xrightarrow{\text{condensation}}\;

R1CH(NH3^+)C(O)NHCH(R2)COO^- \;+\; H2O}

\]

• The –OH from the carboxyl group and a –H from the amino group are removed as a molecule of water.
• The new linkage is –C(=O)–NH–, called a peptide bond.
• The product is a dipeptide; successive additions give a polypeptide and ultimately a protein.

2.2 Mechanistic Details

• Formation proceeds via a tetrahedral intermediate at the carbonyl carbon.
• Resonance between the C=O and C–N bonds gives the peptide bond partial double‑bond character, making it planar and restricting rotation.

2.3 Energetic Considerations

• Peptide‑bond formation is endergonic (unfavourable under standard conditions).
• Living cells couple the reaction to the exergonic hydrolysis of ATP (ΔG°′ ≈ –30 kJ mol⁻¹) via amino‑acyl‑tRNA synthetases:

  1. Amino acid + ATP → amino‑acyl‑AMP + PPi
  2. Amino‑acyl‑AMP + tRNA → amino‑acyl‑tRNA + AMP
  3. The ribosome catalyses peptide‑bond formation, releasing tRNA and H₂O.

3. Peptide‑Bond Breakage (Hydrolysis)

3.1 Overall Reaction

\[

\mathrm{R1CH(NH3^+)C(O)NHCH(R2)COO^- \;+\; H2O

\;\xrightarrow{\text{hydrolysis}}\;

R1CH(NH3^+)COO^- \;+\; H3N^+CH(R2)COO^-}

\]

• Water adds across the peptide bond: the hydroxyl (OH⁻) attacks the carbonyl carbon, and a proton (H⁺) attaches to the nitrogen.
• A tetrahedral intermediate is formed and then collapses, regenerating the original termini.

3.2 Enzyme Catalysis

• Proteases (e.g., pepsin, trypsin, chymotrypsin) provide an active‑site environment that stabilises the tetrahedral intermediate, lowering the activation energy.
• Many proteases employ a catalytic triad (Ser‑His‑Asp) or a catalytic dyad (Cys‑His) to polarise the carbonyl group and activate water for nucleophilic attack.

4. Levels of Protein Structure

5. Functional Case Studies

5.1 Haemoglobin – A Globular, Quaternary Protein

• Composed of four polypeptide chains (2 α + 2 β) – a classic quaternary structure.
• Each chain contains a heme prosthetic group that binds O₂ reversibly.
• Co‑operative binding arises because the quaternary arrangement allows conformational changes (T ↔ R states) that alter the affinity of the remaining subunits.

5.2 Collagen – A Fibrous, Triple‑Helix Protein

• Three polypeptide chains wound around one another to form a triple helix (a specialised secondary structure).
• Each chain follows a repeating Gly‑X‑Y pattern; X and Y are often proline or hydroxyproline, stabilising the helix via hydrogen bonding.
• Multiple triple helices pack together, giving collagen its high tensile strength – essential for skin, bone, and tendon.

6. Structure–Function Relationships & Disease Relevance

• Sickle‑cell disease: a single point mutation (Glu → Val) in the β‑chain of haemoglobin replaces a charged side chain with a hydrophobic one. The altered β‑chains stick together, forming rigid polymers that distort red‑cell shape.
• Prion diseases (e.g., Creutzfeldt–Jakob disease): a normal α‑helical protein (PrP^C) misfolds into a β‑sheet‑rich isoform (PrP^Sc), which aggregates and is resistant to proteolysis, leading to neurodegeneration.
• Enzyme specificity depends on the precise tertiary (active‑site geometry) and quaternary (subunit arrangement) structures; even a small change in side‑chain chemistry can abolish activity.

7. Summary of Peptide‑Bond Formation & Hydrolysis

8. Post‑Translational Modifications (Brief Overview)

• Phosphorylation – addition of a phosphate group (usually to Ser, Thr or Tyr) alters charge and can switch enzyme activity on/off.
• Glycosylation – attachment of carbohydrate chains; important for protein folding, stability and cell‑cell recognition.
• Acetylation, methylation, ubiquitination – modify lysine residues, influencing DNA‑binding proteins, protein turnover, and signalling pathways.

9. Key Points to Remember

• All amino acids share the same backbone; the side chain R confers individual properties.
• At physiological pH the amino group is –NH₃⁺ and the carboxyl group is –COO⁻.
• The peptide bond is planar, has partial double‑bond character, and restricts rotation – a prerequisite for regular secondary structures.
• Peptide‑bond formation is endergonic; cells drive it forward by coupling to ATP hydrolysis via amino‑acyl‑tRNA synthetases.
• Hydrolysis of peptide bonds releases energy and is catalysed by proteases that stabilise a tetrahedral transition state.
• Disulfide bridges (–S–S–) are covalent links that stabilise tertiary and quaternary structures, especially in extracellular proteins.
• Understanding peptide‑bond chemistry underpins the four levels of protein structure and explains how sequence determines function, health, and disease.