2. Amino Acids and Peptides

Amino Acids and Peptides

  • There are 20 amino acids used for protein synthesis.
  • Amino acids are building blocks of peptides and proteins.
    • Peptides are shorter polymers of amino acids.
    • Proteins are longer polymers of amino acids.

Amino Acid Structure

  • Monomer Structure:
    • Acetic or carboxy group.
    • Amino group on the alpha carbon.
    • Side chains (R groups) that differ among amino acids.

Peptide Structure

  • Polymers consist of multiple amino acids linked together.
  • Example: A polymer with four amino acids is a peptide.

Chirality

  • Amino acids are chiral around the alpha carbon.
  • Asymmetric molecules have L and D isomers (mirror images).
  • Proteins contain amino acids in the L configuration.

Acid-Base Properties

  • Amino acids have weak acidic and basic groups.
  • Carboxyl group:
    • Deprotonates (loses a proton) at pH > 2.
  • Amino group:
    • Protonates (gains a proton) at pH < 9.
  • At intermediate pH levels (including neutral pH of 7):
    • Both groups are ionized.
    • Amino acid has both positive and negative charges.
  • Zwitterions:
    • Molecules with two opposite charges.

Peptide Bond Formation

  • Formed by covalent linkage of:
    • Carboxyl group of one amino acid.
    • Amino group of a second amino acid.
  • Amide bonds:
    • General term for carboxyl-amino linkage.
  • Peptide bonds:
    • Specifically refer to linkages of amino acids.
  • Formation involves the loss of a water molecule (H2OH_2O).

Polypeptide Characteristics

  • Defined by:
    • Number of amino acids.
    • Specific sequence of amino acids.
  • R represents the rest of the amino acid molecule.

Polypeptide as Zwitterion

  • N-terminal amino group: positively charged.
  • C-terminal carboxy group: negatively charged.

Protein/Peptide Length

  • Most proteins: 50 to 200 amino acid residues.
  • Shorter chains: peptides or oligopeptides.
  • Peptides as hormones: Some peptides can act as hormones.

Side Chain Importance

  • Side chains provide unique properties to the polypeptide or protein.

Leu-Enkephalin Example

  • Pentapeptide (five amino acids).
  • Opioid peptide modulates pain perception.
  • Sequence: tyrosine, glycine, glycine, phenylalanine, leucine.
  • Tyrosine and phenylalanine: aromatic side chains.
  • Glycine: hydrogen side chain.
  • Leucine: branched side chain.

Directionality

  • Importance of directionality: Reversing the sequence changes the molecule's effect.
  • Example: reversing leu-enkephalin sequence eliminates opioid effect.

Amino Acid Repertoire

  • Proteins are synthesized from 20 amino acids.
  • All are alpha amino acids (amino group on carbon adjacent to carboxyl carbon).
  • All have the L stereochemical structure.

Side Chain Properties

  • Nonpolar side chains (approximately half).
  • Polar but uncharged side chains.
  • Positively or negatively charged side chains.

Amino Acid Codes

  • Three-letter code (straightforward).
  • One-letter abbreviation (used by molecular biologists).
  • Example: Tryptophan is TRP (three-letter) and W (one-letter).

Nonpolar Amino Acids

  • Glycine and alanine: simplest.
    • Glycine: hydrogen side chain.
    • Alanine: methyl group side chain.
  • Valine, leucine, and isoleucine: longer hydrocarbon groups, branched chains.

More Nonpolar Amino Acids

  • Proline: side chain forms a ring structure with the nitrogen on the alpha carbon (technically an amino acid).
  • Methionine and cysteine: contain sulfur.
    • Cysteine: sulfur is present as a sulfhydryl group, which can react with other sulfhydryl groups.
    • Methionine: sulfur atom is methylated.

Aromatic Amino Acids

  • Phenylalanine, tyrosine, and tryptophan: aromatic rings.
  • Aromatic: hydrocarbon ring with alternating single and double bonds.
  • Phenylalanine and tryptophan: nonpolar and hydrophobic.
  • Tyrosine: similar to phenylalanine, but has a hydroxyl group (more polar).
  • Tryptophan: complex structure with two fused rings.

Charged Amino Acids

  • Side chains contain groups that are ionized at physiological pH.
  • Acidic amino acids: aspartate and glutamate.
    • Additional carboxyl group with a negative charge.
  • Basic amino acids: lysine and arginine.
    • Additional nitrogen groups and a net positive charge.
    • Lysine: Second amino group.
    • Arginine: Three nitrogens covalently bonded to the same carbon.

Histidine

  • Ring structure with two nitrogen and three carbon atoms (not aromatic).
  • At pH slightly below 7, accepts an additional hydrogen ion and acquires a positive charge.
  • pKa is near 6, so both charged and non-charged forms are present at neutral pH.
  • Often found in the active site of enzymes.
  • Ability to bind and release protons contributes to catalysis.

Polar But Non-Ionized Amino Acids

  • Serine and threonine: hydroxyl groups.
  • Tyrosine: aromatic and polar amino acid.
  • Asparagine and glutamine: derived from aspartate and glutamate.
    • Amino group in amide linkage on the side chain carboxyl group.
    • Highly polar hydrophilic side chain, but cannot ionize at physiological pH.

Leu-Enkephalin Reexamined

  • Contains two large aromatic side chains (phenylalanine and tyrosine).
  • One branched chain amino acid (leucine).
  • Two small nonpolar glycines.

Importance of Side Chains

  • Provide unique properties of the molecule.
  • Determine specificity for interacting with other molecules.
  • Determine overall structure of larger proteins and polypeptides.
  • In enzymes, determine substrate specificity and are key components of the catalytic mechanism.

Cystine and Disulfide Bonds

  • Sulfhydryl group of cysteine plays a major role in stabilizing protein structure.
  • Oxidation of two sulfhydryl groups results in the formation of a disulfide bridge linking two cysteine side chains together.
  • Removal of two hydrogen atoms from the molecule (removal of two electrons and two accompanying protons or hydrogen ions).

Vasopressin Example

  • Small peptide hormone that stimulates the kidney to reabsorb water.
  • Contains nine amino acids with a disulfide bridge between the two cysteine residues.
  • Net charge of zero with one positively charged side chain (arginine) and one negatively charged side chain (glutamate).
  • Arginine is shown in more detail because this figure is part of a discussion of the use of a synthetic peptide analog as a drug for people who do not synthesize sufficient hormone.

Insulin Example

  • Hormone secreted by the beta cells of the pancreas to regulate blood sugar levels.
  • Two peptide chains (21 and 30 amino acids long) with different amino acid sequences.
  • Chains are attached by two disulfide bridges.
  • A chain also contains a disulfide bridge that forms a loop within the A chain.