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.