Structure and Properties of Amino Acids

Structure and Properties of Amino Acids

Learning Outcomes

• Distinguish between L- and D-amino acids and recognize their structural differences.

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

• Draw and recognize the 20 naturally occurring L-amino acids (ignoring side chain stereochemistry).

• Describe the importance of amino acid modifications.

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

• Interpret amino acid titration curves and calculate pI values given the pKa values of titratable groups.

The Four Classes of Biological Macromolecules

Overview

Biological macromolecules are large, complex molecules essential for life. They are polymers made from specific monomeric units:

• Proteins – monomers: amino acids

• Nucleic acids – monomers: nucleotides

• Carbohydrates – monomers: sugars

• Lipids – monomers: acetate (not always true polymers, but grouped for their biological roles)

Common features of all biological macromolecules:

• Possess three-dimensional structures critical for function.

• Are flexible and dynamic, allowing interaction with other biomolecules and adaptation to environmental changes, modifications, or ligand binding.

Functions of Proteins

Major Roles

• Enzymes: Catalyze biochemical reactions.

• Storage and Transport: Store and move molecules (e.g., hemoglobin transports oxygen).

• Membrane Channels: Facilitate transport across membranes.

• Structural Components: Provide support in cells, organelles, and tissues (e.g., collagen).

• Mechanical Motors: Enable movement of cells and cellular components (e.g., myosin in muscle).

• Regulators: Control gene expression and replication.

• Receptors: Mediate cell signaling and communication.

• Specialized Functions: Include antibodies (immune response) and hormones (signaling).

Structure of Amino Acids

General Structure

Amino acids are the monomers of proteins. Each amino acid contains:

• An amino group (–NH2), a carboxyl group (–COOH), a hydrogen atom, and a unique side chain (R group) attached to the α-carbon.

• At physiological pH (~7.4), amino acids exist as zwitterions (both positive and negative charges, net zero charge): $\ce{H3N^+-CHR-COO^-}$

• The amino group is a weak base (pKa ≈ 9–10), and the carboxyl group is a weak acid (pKa ≈ 2–3).

Ionization States

• At low pH (acidic), the amino acid is fully protonated and positively charged.

• At high pH (alkaline), the amino acid is deprotonated and negatively charged.

• At intermediate pH (near pI), the amino acid is a zwitterion.

Amino Acid Stereochemistry

Chirality and Isomerism

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

• This leads to two enantiomers: L- and D-amino acids, which are non-superimposable mirror images.

• In biological systems, only L-amino acids are incorporated into proteins.

• Emil Fischer established the D/L system based on the optical activity of glyceraldehyde.

Fischer Projections are used to represent stereochemistry. In the L-form, the amino group is on the left; in the D-form, it is on the right.

Mnemonic for L-Amino Acids

• Looking down the H–Cα bond, the groups spell "CORN" (COOH, R, NH2) in a clockwise direction for the L-enantiomer.

R/S System

• Assigns priorities to substituents by atomic number.

• If the sequence from highest to lowest priority is clockwise, the configuration is R; if counterclockwise, it is S.

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

Chemical Properties of Amino Acids

Categories Based on Side Chains

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

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

• Charged:

  • Acidic: Asp, Glu

  • Basic: Lys, Arg, His

• Aromatic: Phe, Tyr, Trp

The side chain determines the amino acid's chemical reactivity, hydrophobicity, and role in protein structure.

Examples and Special Cases

• Proline: Only cyclic amino acid; often found in cis peptide bonds.

• Cysteine: Can form disulfide bonds, stabilizing protein structure.

• Glycine: No side chain; not chiral; provides flexibility.

• Methionine: Contains sulfur; hydrophobic.

Spectroscopic Properties

• All amino acids absorb UV light at ~200 nm due to the peptide bond.

• Aromatic amino acids (Phe, Tyr, Trp) absorb at ~280 nm; this property is used to quantify protein concentration using the Beer-Lambert Law:

$A = \varepsilon c l$

• $A$ = absorbance

• $\varepsilon$ = molar absorptivity (M-1cm-1)

• $c$ = concentration (M)

• $l$ = path length (cm)

Acid-Base Properties and Titration Curves

Ionization and pI

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

• For amino acids without ionizable side chains:

  • $pI = \frac{pK_a^{(\text{COOH})} + pK_a^{(\text{NH}_3^+)} }{2}$

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

Titration Curve Example: Glycine

• At low pH: $\ce{H3N^+-CH2-COOH}$ (net +1 charge)

• At pH ~2.4: $pK_a$ of carboxyl group; half protonated, half deprotonated

• At pH ~6.1: pI, zwitterion ($\ce{H3N^+-CH2-COO^-}$, net 0 charge)

• At pH ~9.8: $pK_a$ of amino group; half protonated, half deprotonated

• At high pH: $\ce{H2N-CH2-COO^-}$ (net -1 charge)

Buffering Regions

• Amino acids buffer best at pH values near their pKa values.

• For glycine, buffering occurs near pH 2.4 and 9.8.

Table: Classification of Amino Acids by Side Chain Properties

Category	Amino Acids	Key Properties
Hydrophobic (Non-polar)	Gly, Ala, Val, Leu, Ile, Met, Pro	Non-polar side chains, often found in protein interiors
Polar (Uncharged)	Ser, Thr, Cys, Asn, Gln	Can form hydrogen bonds, often on protein surfaces
Acidic (Negatively charged)	Asp, Glu	Carboxylate side chains, negatively charged at neutral pH
Basic (Positively charged)	Lys, Arg, His	Side chains accept protons, positively charged at neutral or slightly acidic pH
Aromatic	Phe, Tyr, Trp	Ring structures, absorb UV light at 280 nm

Post-Translational Modifications

• Amino acids in proteins can be chemically modified after translation, increasing functional diversity.

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

Summary

• Amino acids are the building blocks of proteins, with diverse structures and chemical properties.

• Their side chains determine their role in protein structure and function.

• Understanding their ionization, stereochemistry, and modifications is essential for biochemistry.