Lecture 6 Amino Acids: Structures, Stereochemistry, and Acid-Base Properties

Amino Acid Structure and Stereochemistry

• Amino acids contain amino and carboxylic acid functional groups.
• Alpha ($\alpha$) amino acids have both functional groups attached to the same carbon.
• In CHEM 191, 'amino acids' refers specifically to alpha amino acids.

Classification of Amino Acids

• Amino acids are named based on their side chain (R group).
• Naturally occurring amino acids in humans are the L enantiomer.
• There are 20 common amino acids.

Stereochemistry

• All amino acids except glycine have a chiral carbon atom (stereogenic center).
• Chiral molecules exist as enantiomers.
• Glycine (R = H) is achiral and exists in only one form.

L-Isomers and Fischer Projections

• Natural amino acids are L-isomers with the same 3D arrangement of functional groups.
• Fischer projections represent 3D structure:
  • Carboxylic acid (COOH) is at the top.
  • The R group is at the bottom.
  • The chiral carbon is the intersection.
  • Vertical bonds project into the page.
  • Horizontal bonds project out of the page.

D and L configurations

• In a Fischer projection, the L-amino acid has the $NH_2$ group on the left.
• The D-amino acid configuration has the $NH_2$ group on the right.

R,S Configuration

• Stereochemistry can also be defined using the R, S system.
• Priority sequence example (Alanine): NH2 > COOH > CH3 > H.
• View from the side opposite H.
• If trace $NH<em>2$ → COOH → $CH</em>3$ is anticlockwise, stereochemistry is S.
• $CH_2-SH$ group has higher priority than COOH:
  • NH2 > -CH2-SH > COOH > H.
• L-cysteine is the R stereoisomer despite the same spatial arrangement as alanine.

Naming Conventions

• Shorthand naming conventions:
  • Glycine: gly (G), R=H
  • Alanine: ala (A), R=$CH_3$
  • Serine: ser (S), R=$CH_2OH$
  • Cysteine: cys (C), R=$CH_2SH$
  • Aspartic acid: asp (D), R=$CH_2COOH$
  • Lysine: lys (K), R=$(CH<em>2)</em>4-NH_2$

Chemistry of Amino Acids

• Governed by the amino group, the carboxylic acid group, and the side chain (R group).
• Amino acids have acidic and basic functional groups in proximity.
• Amino and carboxylic acid groups are ionized depending on the pH.
• Alpha-amino group is protonated when charged (+ve).
• Alpha-carboxyl acid group is deprotonated when charged (-ve).
• pKa1 refers to $pK<em>a$ of the carboxylic acid group. pKa2 refers to $pK</em>a$ of the amino group.
  • For Ala, $pK<em>{a1} = 2.4$, $pK</em>{a2} = 9.8$

Acid-Base Properties and Titration

• Titration measures and visualizes acid-base properties.

Zwitterions and Isoelectric Point (pI)

• A zwitterion is an overall neutral molecule with positive and negative charges.
• At the isoelectric point (pI), the amino acid is a zwitterion at maximum concentration.
• The isoelectric point is when the amino acid has no net electrical charge.

Calculating pI

• For amino acids with non-ionizable side chains, pI is the average of the amino and carboxylic acid pKa values.
  • Glycine $pI = (2.35 + 9.60) / 2 = 5.98$
• At a pH of 5.98, glycine exists predominantly as a zwitterion.

pI with Different Side Chains

• Amino acids with acidic or basic side chains have three ionizable functional groups.
• For amino acids with acidic or basic R groups:
  • pI is the average of the two closest pKa values.
• The ionization of functional groups can change depending on the pH of the environment, which can affect solubility and activity.

Determining Dominant Amino Acid Form at a Given pH

• Approximating ionization at a given pH:
  • If pKa = pH, then 50% of the functional group is ionized.
  • When pH and pKa are approximately 1 unit apart, the ratio is approximately 90/10%.
  • When pH and pKa are approximately 2 units apart, the ratio is approximately 99/1%.

Examples of Ionization at Different pH Levels

• Stomach pH = 2
• Plasma pH = 7.4

Stomach, pH = 2

• pH is approximately equal to $pK_{a1}$
• pH is approximately 2 units lower than $pK_{a3}$
• pH is approximately 8 units lower than $pK_{a2}$

Plasma, pH = 7.4

• pH is approximately 5 units higher than $pK_{a1}$
• pH is approximately 4 units higher than $pK_{a3}$
• pH is approximately 2 units lower than $pK_{a2}$

Drawing Amino Acids in Neutral Form

• Convention dictates drawing amino acids in neutral form.
• Ionized forms dominate in solution and influence the chemistry of amino acids.