Biochemistry: A Short Course 2

Amino Acids: Structure and Properties

General Structure of Amino Acids

Amino acids are the fundamental building blocks of proteins. Each amino acid consists of a central tetrahedral carbon atom (the alpha carbon) bonded to four distinct groups:

• An amino group (–NH2)

• A carboxylic acid group (–COOH)

• A hydrogen atom

• A distinctive side chain (R group)

Except for glycine, all amino acids have a chiral alpha carbon, meaning they exist as stereoisomers. Only the L-isomer is found in natural proteins. All proteins are constructed from the same set of 20 standard amino acids.

Classification of Amino Acids by Side Chain Properties

The 20 standard amino acids are classified based on the chemical properties of their side chains (R groups). This classification is important for understanding protein structure and function.

• Hydrophobic (Nonpolar) Side Chains: Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline, Phenylalanine, Tryptophan

• Polar (Uncharged) Side Chains: Serine, Threonine, Tyrosine, Cysteine, Asparagine, Glutamine

• Positively Charged (Basic) Side Chains: Lysine, Arginine, Histidine

• Negatively Charged (Acidic) Side Chains: Aspartic acid, Glutamic acid

Example: The aromatic amino acids (phenylalanine, tyrosine, tryptophan) contain ring structures that absorb ultraviolet light, which is useful in protein quantification assays.

Essential Amino Acids

Essential amino acids are those that cannot be synthesized by the human body and must be obtained from the diet. Most microorganisms can synthesize all 20 amino acids, but humans require dietary intake of several.

• Examples of essential amino acids: Valine, Leucine, Isoleucine, Methionine, Phenylalanine, Tryptophan, Threonine, Lysine, and Histidine (especially essential in children).

Ionization Properties of Amino Acids: The Case of Histidine

Histidine and Its Imidazole Side Chain

Histidine is unique among amino acids because its side chain contains an imidazole ring with a pKa around 6. This allows the side chain to be either positively charged or neutral at physiological pH, making histidine important in enzyme active sites.

• At pH values below the pKa, the imidazole ring is protonated (positively charged, His+).

• At pH values above the pKa, the ring is deprotonated (neutral, His).

Example: In the enzyme chymotrypsin, histidine plays a key role in catalysis due to its ability to accept or donate a proton near physiological pH.

Ionization Reaction and Acid-Base Identification

The ionization of the imidazole side chain can be represented as:

$\mathrm{His}^+ \rightleftharpoons \mathrm{His} + \mathrm{H}^+$

• Acid: The charged form (His+) can donate a proton.

• Base: The uncharged form (His) can accept a proton.

The Henderson-Hasselbalch Equation

The Henderson-Hasselbalch equation relates the pH of a solution to the pKa of an acid and the ratio of the concentrations of its conjugate base and acid forms:

$\mathrm{pH} = \mathrm{p}K_a + \log \left( \frac{[\text{Base}]}{[\text{Acid}]} \right)$

For histidine's imidazole side chain:

$8.0 = 6.0 + \log \left( \frac{[\mathrm{His}]}{[\mathrm{His}^+]} \right)$

Solving for the ratio:

$2 = \log \left( \frac{[\mathrm{His}]}{[\mathrm{His}^+]} \right)$

$100 = \frac{[\mathrm{His}]}{[\mathrm{His}^+]}$

This means that at pH 8, the base (neutral His) is 100 times more abundant than the acid (His+), so the probability of finding the protonated form is about 0.9%.

Key Terms

• Side chain (R group): The variable group attached to the alpha carbon of an amino acid, determining its properties.

• L-amino acid: The stereoisomer of amino acids found in proteins.

• Dipolar ion (zwitterion): A molecule with both positive and negative charges but overall neutral, as seen in amino acids at physiological pH.

• Essential amino acids: Amino acids that must be obtained from the diet.