Biochemistry 214 Theme D: Proteins - Lecture 1 Notes

Definition: Proteins are polymers of L-isomers of 20 α-amino acids.
Building Blocks: Each α-amino acid differs based on its unique side-chain.
Chemical Structure: Proteins are formed by covalently linking amino acids through peptide bonds to create polypeptides.

Zwitterions: Amino acids exist as zwitterions, which are molecules that have both positive and negative charges but are overall neutral.
Weak Acids/Bases: They can act as weak acids and bases due to their functional groups.
Biochemical Roles: Amino acids play a diverse range of roles in living systems, including:
   - Structural components in cells (e.g., collagen).
   - Enzymatic activity (enzymes catalyze biological reactions).
   - Transport and storage of molecules.
   - Regulatory functions (hormones and receptors).
   - Genetic information processing (transcription factors).
   - Defense mechanisms (immune system components).

Functional Groups:
  - Amino Group:
    - Structure: -NH₂ (can become -NH₃⁺ in zwitterion form).
    - Characteristics: Polar, weak base, participates in peptide bonds.
  - Carboxyl Group:
    - Structure: -COOH (can become -COO⁻ in zwitterion form).
    - Characteristics: Polar, weak acid, resonance-stabilized, participates in peptide bonds.
  - Unique Side-Chain: 20 different groups determining the identity of each amino acid.
Chirality: The α-carbon is a chiral center, leading to enantiomers (L- and D-forms).

Structural Functions: Fibrous proteins (e.g., collagen) provide structure.
Dynamic Functions: Globular proteins enable dynamic processes in tissues and cells.
Variety of Roles:
  - Enzymes: Catalyze nearly all biological reactions.
  - Motor Proteins: Enable movement in muscles and flagella.
  - Transport Proteins: Assist in storage and transport of molecules.
  - Regulatory Proteins: Involved in biochemical regulation.
  - Defense Proteins: Protect the body, e.g., antibodies.

Properties:
  - Polar with dipole-ion characteristics.
  - Weak acid with a pKa typically around 1.8-2.4.
  - Participates in peptide bond formation and non-covalent interactions (H-bonds, ion-dipole).

Properties:
  - Polar with dipole-ion characteristics.
  - Weak base with a pKa typically around 9.0-10.7.
  - Also plays a role in peptide bonds and non-covalent interactions.

Definition: A zwitterion is an iso-electric species, neutral in charge.
pH at Neutrality: Carboxylic acid group (-COO⁻) and amino group (-NH₃⁺) are both ionized at physiological pH (approximately 7).
Amphiprotic Nature: Can act as a buffer in biological systems.

An α-amino acid has four distinct groups bonded to a central carbon, making it chiral.
Fischer Projection: Used to represent chiral centers, with vertical bonds going back and horizontal bonds coming forward.
Enantiomers: L-isomers are the naturally occurring amino acids in proteins; D-isomers are rare.

Racemization: The conversion between L-isomers and D-isomers.
Optical Activity: Enantiomers have identical physical properties but differ in how they rotate plane-polarized light.
Van't Hoff Rule: For a molecule with n chiral carbons, the number of isomers is given by $2^n$ .
Example: Cystine has two chiral centers.

Based on the absolute configuration of glyceraldehyde.
D- and L- Configuration: Identified by the position of hydroxyl (-OH) group on the last carbon.

Similarly developed conventions for amino acids using serine as reference.
Position of the amino group compared to the chiral carbon helps determine D- or L- form:
- NH₃⁺ group on the right indicates D-config.
- NH₃⁺ group on the left indicates L-config.

Dominance of L-isomers leads to:
- Specificity in protein interactions (enzyme-substrate, neurotransmitter-receptor, drug binding).
- Asymmetry in protein structure enhancing secondary structures, like α-helixes and β-sheets.