Amino Acids and Peptides Notes

Amino Acids and Peptides

Basic Concepts

  • Amino acids are the basic building blocks of peptides and proteins.
  • Peptides are shorter polymers of amino acids, while proteins are longer polymers.
  • All amino acids have:
    • A carboxyl group (-COOH), which is an acid group.
    • An amino group (-NH3) on the alpha-carbon.
  • Amino acids differ in their side chains, which are denoted as "R".

Chirality of Amino Acids

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

Ionization in Solution

  • At neutral pH, amino acids exist as zwitterions, possessing both positively and negatively charged functional groups.
    • Carboxyl group: R-COO-
    • Amino group: R-NH3+

Peptide Bond Formation

  • A peptide bond forms between the carboxyl group of one amino acid and the amino group of another.
  • The formation of a peptide bond is accompanied by the loss of a water molecule (H2OH_2O).

Polypeptide Chains

  • A polypeptide chain has direction or polarity.
  • Each chain has a specific sequence of amino acids (R1, R2, R3…) from the amino end to the carboxyl end.
  • Most proteins have polypeptide chains containing 50 to 200 amino acid residues.
  • Shorter chains are called peptides or oligopeptides.
  • Some peptides function as hormones.

Side Chain Properties

  • Side chains give amino acids their unique properties.
  • Leu-enkephalin, a pentapeptide, is an opioid peptide that modulates pain perception.
  • Two amino acids have side chains with different ring (aromatic) structures.
  • Two amino acids have only a hydrogen side chain.
  • The carboxyl amino acid has a branched chain side group.

Repertoire of Amino Acids

  • Proteins are built from a repertoire of 20 amino acids with different side chains.
  • Some amino acid side chains have positive or negative charges at physiological pH.
  • Some uncharged side chains are polar; others are nonpolar or hydrophobic.
  • Three-letter (Ala) or one-letter (A) abbreviations are used for each amino acid (e.g., alanine).

Non-Polar Amino Acids

  • Glycine and alanine are the simplest amino acids.
  • Valine, leucine, and isoleucine are “branched-chain” amino acids.
  • The side chain of proline is bonded to the nitrogen as well as the α-carbon.
  • Methionine and cysteine are sulfur-containing amino acids.

Aromatic Amino Acids

  • Phenylalanine, tyrosine, and tryptophan have side chains with aromatic ring structures.
  • Phenylalanine (Phe) and tryptophan (Trp) are relatively nonpolar.
  • The hydroxyl group on the ring of tyrosine confers 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. The side chain nitrogen is positively charged at neutral pH.

Histidine

  • Histidine has a ring structure containing two nitrogen atoms.
  • When the second nitrogen on the ring becomes protonated, the side chain has a net positive charge.
  • Histidine has a pKa near 6, meaning that charged and non-charged forms are both present at neutral pH.
  • The percentage of the protonated form increases 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 amides, derived from aspartate and glutamate, respectively, by the addition of NH3NH_3 to the carboxyl group on the side chain.

Side Chains and Molecular Properties

  • All polypeptides have a similar peptide bond backbone.
  • Side chains provide the unique properties of the molecule and its specificity for interacting with other biological molecules.
  • In larger polypeptides or proteins, the side chains determine the nature of the overall structure of the molecule.
  • In enzymes, amino acid side chains determine substrate specificity and are key components of the catalytic mechanism.

Cysteine and Disulfide Bonds

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

Vasopressin

  • Vasopressin is a small peptide hormone with only nine amino acids.
  • It stimulates water reabsorption in the kidney and prevents dehydration.
  • There is a disulfide bond between the two cysteine residues.

Insulin

  • Insulin is a larger polypeptide hormone that stimulates glucose utilization and cell growth.
  • The mature insulin molecule has two polypeptide chains held together by disulfide bridges.
  • There is also one disulfide bridge within the A chain.