Amino Acids: Structure and Classification

Amino Acids

• The building blocks of proteins
• Contain an amino group (NH2), a carboxyl group (COOH), a central carbon atom (α-carbon), a hydrogen atom (H), and an R-group (side chain).
• R-group is the variable part that distinguishes one amino acid from another
• Almost all naturally occurring amino acids have the (S) configuration and are called L-amino acids
• Amino acids have properties of both amines and carboxylic acids
• 20 common amino acids found in proteins are called standard amino acids
• All standard amino acids are L-amino acids.

Classification of amino acids

• Nonpolar (Hydrophobic) Amino Acids:
  • Nonpolar R-groups which do not interact well with water
  • Found in the interior of proteins
  • Examples: glycine, alanine, valine, leucine, isoleucine, proline, methionine, and phenylalanine.
• Polar (Hydrophilic) Amino Acids:
  • Polar R-groups that interact favorably with water
  • Found on the surface of proteins
  • Form hydrogen bonds with water and other polar molecules
  • Examples: serine, threonine, tyrosine, asparagine, glutamine, and cysteine.
• Aromatic Amino Acids:
  • Aromatic ring in their R-groups
  • Participate in pi-pi stacking interactions
  • Involved in the structural stability of proteins.
  • Examples: phenylalanine and tyrosine.
• Acidic (Negatively Charged) Amino Acids:
  • Carboxyl groups (COOH) in their R-groups
  • Donate protons (H+)
  • Carry a net negative charge at physiological pH
  • Examples: aspartic acid (aspartate) and glutamic acid (glutamate)
• Basic (Positively Charged) Amino Acids:
  • Amino groups (NH2) in their R-groups
  • Accept protons (H+)
  • Carry a net positive charge at physiological pH.
  • Examples: lysine, arginine, and histidine.
• Sulfur-Containing Amino Acids:
  • Contain sulfur in their R-groups
  • Examples: cysteine and methionine

Ionization States of Amino Acids

• At low pH, the amino acid exists primarily in its cationic form:
  $NH_3^+-R-COOH$
• Zwitterionic Form (pKa1 < pH < pKa2):
  • As the pH rises, the carboxyl group loses a proton, leading to the zwitterionic form:
    $NH_3^+-R-COO^-$
  • This is typically the dominant form around the isoelectric point (pI)
• Fully Deprotonated Form (pH > pKa2):
  • At high pH, the amino group can lose a proton, resulting in a negatively charged species: $NH_2-R-COO^-$

pKa Values & Titration Curves

• Each amino acid has specific pKa values:
  • $pK_a1$: Dissociation of the carboxyl group (typically around 2).
  • $pK_a2$: Dissociation of the amino group (typically around 9).
  • $pK_a3$: For amino acids with ionizable side chains, this represents the side chain’s dissociation (e.g., for aspartic acid, around 4.0).
• Titration curves show how the charge changes with pH.
• Buffer Region: The amino acid resists changes in pH due to the presence of both protonated and deprotonated forms.
• Inflection Points: Correspond to pKa values, indicating where significant changes in charge occur.
• Ionization is important for:
  • Biological Activity
  • Enzyme Function
  • Separation Techniques

Isoelectric Point (pI)

• The pH at which an amino acid has no net charge.
• At this point, the positive and negative charges are balanced, and the molecule exists predominantly in its zwitterionic form.
• Calculating pI:
  • For amino acids with two functional groups (like the standard amino acids):
    $pI = \frac{pK_a1 + pK_a2}{2}$
    Where:
    • $pK_a1$ is the dissociation constant of the carboxyl group
    • $pK_a2$ is the dissociation constant of the amino group
  • For amino acids with ionizable side chains (like glutamic acid or lysine), the pI calculation will involve the pKa values of the side chain as well.
• pI and Solubility: Less soluble in water.
• Applications:
  • Protein purification techniques (like isoelectric focusing)
  • Protein stability and function

Stereoisomers of Amino Acids

• All amino acids, except glycine, have four different groups arranged tetrahedrally around the central C atom.
• Can exist in two stereoisomers (enantiomers): D and L forms
• Stereoisomers are nonsuperimposable, mirror images
• Distinguishable based on their different optical rotation of plane-polarized light
• Only L-amino acids are found in proteins.

Proteins

• Complex macromolecules that play a wide range of essential roles in living organisms
• Their structure can be described at multiple levels: primary, secondary, tertiary, and quaternary

Primary Structure

• Linear sequence of amino acids in the polypeptide chain
• Determined by the genetic code
• Unique to each protein
• Mutations in the primary structure can affect protein function

Secondary Structure

• Local three-dimensional arrangements of amino acids in a protein chain
• Two common secondary structures: alpha helices and beta sheets
• Alpha helices: Coiled structures held together by hydrogen bonds
• Beta sheets: Extended, sheet-like structures stabilized by hydrogen bonds
• Important for the overall folding of a protein

Tertiary Structure

• Overall three-dimensional shape of a protein
• Results from interactions between amino acid side chains (R-groups)
• Interactions include:
  • Hydrogen bonds
  • Disulfide bonds
  • Hydrophobic interactions
  • Ionic interactions
• Essential for a protein’s function
• Determines its active sites and binding sites

Quaternary Structure

• Some proteins are composed of multiple polypeptide chains, or subunits
• Arrangement and interactions of these subunits are critical for the protein’s function
• Example: Hemoglobin is a tetrameric protein with four subunits.

Test your knowledge on amino acids, the building blocks of proteins. This quiz covers their structure, classification into polar and nonpolar categories, and the significance of their R-groups. Challenge yourself to identify different types of amino acids and their properties.