Structure and Properties of Amino Acids

Learning Outcomes

• Distinguish between L- and D-amino acids based on structure and stereochemistry.

• Recall the names, three-letter codes, and single-letter codes of all 20 naturally occurring amino acids.

• Recognize the structural features of the 20 L-amino acids.

• Understand the importance of amino acid modifications in proteins.

• Describe the chemical properties of amino acids: acid/base chemistry, hydrophobicity, hydrophilicity, hydrogen bonding, nucleophilicity, and electrophilicity.

• Interpret amino acid titration curves and calculate isoelectric points (pI) using pKa values.

The Four Classes of Biological Macromolecules

Overview

Biological macromolecules are essential polymers in living systems, each composed of specific monomeric units:

• Proteins – composed of amino acids

• Nucleic acids – composed of nucleotides

• Carbohydrates – composed of sugars

• Lipids – derived from acetate units

All biological macromolecules share these features:

• Three-dimensional structures critical for function

• Flexibility to interact with other biomolecules

• Dynamism – ability to change shape in response to environment, modifications, or ligand binding

Functions of Proteins

Major Roles

• Enzymes – catalyze biochemical reactions

• Storage and transport of molecules

• Membrane channels for selective transport

• Structural components of cells, organelles, and tissues

• Mechanical motors for movement

• Regulation of gene expression (transcription, translation, replication)

• Receptors for cell signaling and communication

• Specialized functions (e.g., antibodies, hormones)

Structure of Amino Acids

General Structure

Each amino acid contains:

• An amino group (–NH2 or –NH3+)

• A carboxyl group (–COOH or –COO–)

• A side chain (R group) unique to each amino acid

• A central α-carbon (Cα)

At physiological pH (~7.4), amino acids exist predominantly as zwitterions (both positive and negative charges, net zero charge):

• Amino group is protonated: –NH3+

• Carboxyl group is deprotonated: –COO–

pKa values:

• Amino group: pKa ≈ 9–10 (weak base)

• Carboxyl group: pKa ≈ 2–3 (weak acid)

Amino Acid Stereochemistry

Chirality and Isomerism

• The α-carbon is chiral (except in glycine), attached to four different groups.

• Stereoisomers: Molecules with the same formula but different spatial arrangements.

• L- and D- forms: Most naturally occurring amino acids are in the L-configuration.

• Optical activity: L- and D- forms rotate plane-polarized light in opposite directions.

Fischer Projections: Used to distinguish L- and D- amino acids, referencing L-glyceraldehyde.

Mnemonic: In Fischer projections, with the amino group up and carboxyl group down, if the R group is on the left, it is the L-form.

The R,S System

• Assigns priorities to substituents by atomic number.

• Clockwise arrangement = R; counterclockwise = S.

• Most L-amino acids are S, except cysteine (due to sulfur's higher priority).

Classification of Amino Acids

Categories Based on Side Chain Properties

• Hydrophobic (non-polar): Gly, Ala, Val, Leu, Ile, Met, Pro

• Polar (uncharged): Ser, Thr, Cys, Gln, Asn

• Charged:

  • Positively charged (basic): Lys, Arg, His

  • Negatively charged (acidic): Asp, Glu

• Aromatic: Phe, Tyr, Trp

The side chain determines the chemical and physical properties of each amino acid and the proteins they form.

Table: Amino Acid Categories and Properties

Chemical Properties of Amino Acids

Acid/Base Chemistry

• Amino acids can act as acids or bases depending on pH.

• At low pH: fully protonated (positive charge).

• At high pH: fully deprotonated (negative charge).

• At physiological pH: zwitterion (net zero charge).

Hydrophobicity and Hydrophilicity

• Hydrophobic amino acids cluster away from water.

• Hydrophilic amino acids interact with water and are often found on protein surfaces.

Hydrogen Bonding

• Polar and charged side chains can form hydrogen bonds, stabilizing protein structure.

Nucleophilicity and Electrophilicity

• Nucleophilic side chains (e.g., Ser, Cys, His, Lys) participate in enzyme catalysis.

• Electrophilic centers are less common but can be involved in certain reactions.

Amino Acid Modifications

Post-Translational Modifications

• Amino acids in proteins can be chemically modified after translation.

• Examples: phosphorylation (Ser, Thr, Tyr), hydroxylation (Pro), acetylation (Lys), carboxylation (Glu).

• These modifications alter protein function, localization, or stability.

Titration Curves and Isoelectric Point (pI)

Titration of Amino Acids

• Amino acids have characteristic titration curves due to their ionizable groups.

• Key points on the curve correspond to pKa values of the carboxyl and amino groups (and side chains, if present).

• The isoelectric point (pI) is the pH at which the amino acid has no net charge.

Formula for pI (for amino acids without ionizable side chains):

For amino acids with ionizable side chains, the pI is the average of the two pKa values that surround the neutral species.

Example: Glycine Titration

• pKa,1 (COOH): ~2.4

• pKa,2 (NH3+): ~9.8

• pI = (2.4 + 9.8)/2 = 6.1

Buffering Regions

• Amino acids buffer best near their pKa values.

• At these points, addition of acid or base causes minimal pH change.

Summary Table: Ionization States of Glycine

Additional info:

• Absorbance at 280 nm (UV) is used to estimate protein concentration, primarily due to aromatic amino acids (Phe, Tyr, Trp).

• Disulfide bonds (Cys–Cys) stabilize protein structure, especially in extracellular proteins.

• Mnemonic devices and structural diagrams are helpful for memorizing amino acid structures and codes.