Comprehensive Notes on Amino Acids and Peptide

Amino Acids and Peptides

Amino Acid Basics

  • Amino acids are the fundamental building blocks of peptides and proteins.
  • Peptides are shorter polymers of amino acids, while proteins are longer polymers.
  • Every amino acid contains:
    • A carboxyl group (-COOH), which acts as an acid.
    • An amino group (-NH3) attached to the alpha-carbon.
  • Amino acids are distinguished by their side chains, denoted as R.

Chirality of Amino Acids

  • Only L-amino acids are found in proteins.
  • The alpha carbon (C_[\alpha]) of common amino acids is asymmetrical or chiral.

Ionization of Amino Acids

  • Amino acids in solution at neutral pH exist as zwitterions.
  • Zwitterions have both positively and negatively charged functional groups.
    • Carboxyl group: R-COO-
    • Amino group: R-NH_3+

Peptide Bond Formation

  • A peptide bond is created when the carboxyl group of one amino acid links to the amino group of another.
  • This linkage is accompanied by the removal of a water molecule (H_2O).

Polypeptide Chains

  • Polypeptide chains possess directionality or polarity.
  • Each chain has a unique sequence of amino acids (R1, R2, R3…) extending from the amino end to the carboxyl end.
  • Most proteins consist of polypeptide chains containing 50 to 200 amino acid residues.
  • Shorter chains are termed peptides or oligopeptides.
  • Some peptides function as hormones.

Side Chain Properties

  • Side chains provide unique properties to each amino acid.
  • Leu-enkephalin, a pentapeptide, serves as an opioid, influencing pain perception.
  • Some amino acids contain aromatic ring structures in their side chains.
  • Glycine has a hydrogen side chain.
  • Valine has a branched chain side group.

Amino Acid Repertoire

  • Proteins are constructed from a set of 20 amino acids, each with distinct side chains.
  • Some amino acid side chains carry positive or negative charges at physiological pH.
  • Uncharged side chains can be polar, nonpolar, or hydrophobic.
  • Amino acids are often represented by three-letter (e.g., Ala) or one-letter (e.g., A) abbreviations.

Non-Polar Amino Acids

  • Glycine and alanine are the simplest amino acids.
  • Valine, leucine, and isoleucine are branched-chain amino acids.

More Non-Polar Amino Acids

  • Proline's side chain is bonded to both the nitrogen and the alpha-carbon.
  • Methionine and cysteine are sulfur-containing amino acids.

Aromatic Amino Acids

  • Phenylalanine, tyrosine, and tryptophan have aromatic ring structures in their side chains.
  • Phenylalanine (Phe) and tryptophan (Trp) are relatively nonpolar.
  • Tyrosine's hydroxyl group imparts more polar characteristics.

Charged Amino Acids

  • Aspartate and glutamate are acidic amino acids with a net negative charge at pH 7.
  • Lysine and arginine are basic amino acids; their side chain nitrogen is positively charged at neutral pH.

Histidine's Charge

  • Histidine features a ring structure with two nitrogen atoms.
  • When the second nitrogen is protonated, the side chain gains a net positive charge.
  • Histidine's pKa is near 6, indicating that charged and non-charged forms coexist at neutral pH. The protonated form becomes more prevalent at slightly acidic pH.

Polar Amino Acids

  • Serine and threonine have hydroxyl groups on their side chains. Tyrosine, an aromatic amino acid, also has a hydroxyl group.
  • Asparagine and glutamine are amines derived from aspartate and glutamate, respectively, via the addition of NH_3 to the carboxyl group on the side chain.

Side Chains and Molecular Properties

  • Polypeptides share a similar peptide bond backbone, consisting of bonds between amino acids.
  • Side chains dictate the unique properties of the molecule and its interactions with other biological molecules.
  • In larger polypeptides or proteins, side chains determine the molecule's overall structure.
  • In enzymes, amino acid side chains define substrate specificity and are essential for the catalytic mechanism.

Cysteine and Disulfide Bonds

  • A disulfide bridge can form between two intra- or inter-chain cysteine residues.
  • Disulfide bonds stabilize/create polypeptide conformation.
  • They are common in extracellular and secreted proteins.
  • Disulfide bonds result from the oxidation of sulfhydryl (-SH) groups to form –S-S-.
  • Oxidation involves the removal of hydrogen atoms, or protons (H^+) and electrons (e^-).

Vasopressin

  • Vasopressin is a small peptide hormone comprising nine amino acids that stimulates water reabsorption in the kidney, preventing dehydration.
  • It contains a disulfide bond between two cysteine residues.

Insulin

  • Insulin, a larger polypeptide hormone, promotes glucose utilization and cell growth.
  • The mature insulin molecule consists of two polypeptide chains linked by disulfide bridges, with an additional disulfide bridge within the A chain.