Structure and Properties of Amino Acids: Biochemistry Study Notes

Structure and Properties of Amino Acids

Learning Outcomes

• Distinguish between L- and D- amino acids.

• Recall the name, three-letter code, and single-letter code of all naturally occurring amino acids.

• Recognize the 20 naturally occurring L-amino acids and their structures.

• Describe the importance of amino acid modifications.

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

• Interpret amino acid titration curves and calculate pI values using pKa values.

Proteins: Amino Acids and Chirality

Biological Macromolecules

Proteins are one of the four major classes of biological macromolecules, alongside nucleic acids, carbohydrates, and lipids. Each class is composed of specific monomeric units:

• Proteins: amino acids

• Nucleic acids: nucleotides

• Carbohydrates: sugars

• Lipids: acetate (fatty acids)

All biological macromolecules share common features:

• Three-dimensional structures (difficult to visualize in 2D)

• Structure is critical to function

• Flexibility allows interaction with other biomolecules

• Dynamic nature: change shape in response to environment, modifications, and ligand interactions

Functions of Proteins

• Enzymes: catalyze biochemical reactions

• Storage and transport of molecules

• Membrane channels for transport

• Structural components of cells, organelles, and tissues

• Mechanical motors for movement

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

• Receptors for cell signaling and communication

• Specialized functions: antibodies, hormones

Amino Acid Structure

General Structure

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

• An amino group (–NH2), weak base, pKa ≈ 9–10

• A carboxyl group (–COOH), weak acid, pKa ≈ 2–3

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

• A central α-carbon (chiral except for glycine)

At physiological pH (~7), amino acids exist as zwitterions (both positive and negative charges, net zero charge):

• Amino group is protonated: –NH3+

• Carboxyl group is deprotonated: –COO–

General zwitterion equation:

• $\text{R-NH}_2 + H^+ \rightleftharpoons \text{R-NH}_3^+$ (basic, pK_a 9–10)

• $\text{COOH} \rightleftharpoons \text{COO}^- + H^+$ (acidic, pK_a 2–3)

Chirality and Stereochemistry

The α-carbon of amino acids (except glycine) is chiral, attached to four different groups:

• Amino group

• Carboxyl group

• Hydrogen atom

• Side chain (R group)

This chirality leads to two enantiomers (L and D forms), which are non-superimposable mirror images. In biological systems, only the L-enantiomer is commonly found.

Stereoisomers: molecules with the same chemical formula but different spatial configurations.

Fischer projection is used to represent stereochemistry. Emil Fischer established that amino acids are chiral and rotate plane-polarized light, similar to L-glyceraldehyde.

Distinguishing L- and D- Amino Acids

• L-amino acids: found in proteins of living organisms

• D-amino acids: rare in nature, found in some bacterial cell walls and antibiotics

• Reference is made to L-glyceraldehyde for configuration

Mnemonic: When looking down the H–Cα bond, the arrangement of groups in L-amino acids spells "CORN" clockwise (COOH, R, NH2).

R,S System of Naming Chiral Centers

The R,S system assigns priorities to substituents based on atomic number:

• Highest priority: SH > OH > NH2 > COOH > CHO > CH2OH > CH3 > H

• Configuration is determined by the order of groups when viewed from the lowest priority substituent

• Clockwise: R; Counterclockwise: S

Note: R/S nomenclature is independent of optical activity.

Classification of Amino Acids

Categories Based on Side Chains

The 20 naturally occurring amino acids are classified by the properties of their side chains:

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

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

• Charged: Asp, Glu (negative); Lys, Arg, His (positive)

• Aromatic: Phe, Tyr, Trp

Side chains determine the physical and chemical character of each amino acid and the proteins they form.

Structural Representations and Nomenclature

• Each amino acid has a one-letter and three-letter abbreviation (e.g., Gly/G, Ala/A)

• Carbons in side chains are labeled starting from the α-carbon

Chemical Properties of Amino Acids

Acid/Base Chemistry

Amino acids can act as acids or bases depending on the pH of the environment. The ionization state affects their charge and reactivity.

• pKa values for amino and carboxyl groups determine ionization

• Side chains with ionizable groups (Asp, Glu, Lys, Arg, His, Cys, Tyr) contribute to acid/base properties

Hydrophobicity and Hydrophilicity

• Hydrophobic amino acids: non-polar side chains, often found in protein interiors

• Hydrophilic amino acids: polar or charged side chains, often found on protein surfaces

Hydrogen Bonding

• Polar side chains (Ser, Thr, Asn, Gln) can form hydrogen bonds

• Amide groups (Asn, Gln) are hydrogen bond donors and acceptors

Nucleophilicity and Electrophilicity

• Nucleophilic side chains: Lys (amino), Cys (thiol), Ser/Thr (hydroxyl), His (imidazole)

• Electrophilic side chains: less common, but carbonyl groups can act as electrophiles

Amino Acid Modifications

Post-Translational Modifications

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

• Phosphorylation (e.g., phosphoserine)

• Hydroxylation (e.g., 4-hydroxyproline)

• Acetylation (e.g., N-ε-acetyllysine)

• Carboxylation (e.g., γ-carboxyglutamate)

These modifications regulate protein activity, localization, and interactions.

Amino Acid Titration Curves and pI Calculation

Titration Curves

Titration curves show how the charge of an amino acid changes with pH. Key features include:

• pKa values for ionizable groups

• Buffering regions near each pKa

• Isoelectric point (pI): pH at which net charge is zero

Example: Glycine titration curve

• pKa1 (carboxyl): ~2.4

• pKa2 (amino): ~9.8

• pI = (pKa1 + pKa2)/2 = (2.4 + 9.8)/2 = 6.1

$pI = \frac{pK_{a1} + pK_{a2}}{2}$

Buffering Capacity

• Amino acids buffer best near their pKa values

• Multiple ionizable groups (side chains) create complex titration curves

Summary Table: Amino Acid Categories

Category	Amino Acids	Key Properties
Hydrophobic (Non-polar)	Gly, Ala, Val, Leu, Ile, Met, Pro	Non-polar side chains, interior of proteins
Polar (Uncharged)	Ser, Thr, Cys, Asn, Gln	Hydrogen bonding, surface of proteins
Charged (Acidic)	Asp, Glu	Negative charge at physiological pH
Charged (Basic)	Lys, Arg, His	Positive charge at physiological pH
Aromatic	Phe, Tyr, Trp	Ring structures, absorb UV light (~280 nm)

Additional info:

• Beer-Lambert Law for protein quantification: $A = \varepsilon c l$ where $A$ is absorbance, $\varepsilon$ is molar absorptivity, $c$ is concentration, and $l$ is path length.

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

• Mnemonic devices (e.g., "CORN" rule) can aid in memorizing amino acid stereochemistry.