Chapter 3: Amino Acids

Introduction to Amino Acids

Amino acids are the fundamental building blocks of proteins, which are essential macromolecules in all living organisms. Their unique structures allow for the formation of complex protein architectures and diverse biological functions.

• Definition: Amino acids are organic compounds containing both an amino group (–NH2) and a carboxyl group (–COOH).

• Proteogenic amino acids: The 20 amino acids encoded by the genetic code and incorporated into proteins.

• Essential amino acids: Amino acids that cannot be synthesized by the human body and must be obtained from the diet.

Depicting Biomolecules

Biochemists use various conventions to represent the structure of amino acids and other biomolecules.

• Fischer Projections: Used to show the arrangement of atoms around the central carbon, with vertical bonds projecting away and horizontal bonds toward the viewer.

• Stereochemical Renderings: Used to visualize the three-dimensional shape, with wedge and dashed bonds indicating orientation relative to the plane of the page.

Structure of Amino Acids

All amino acids share a common structure but differ in their side chains (R groups).

• Central (α) carbon bonded to:

  • Amino group (–NH2)

  • Carboxyl group (–COOH)

  • Hydrogen atom

  • Variable R group (side chain)

• Chirality: Most amino acids exist as L- and D- isomers, but only L-amino acids are found in proteins.

Application of L and D Convention

The L and D system is used to classify amino acids based on the position of the amino group in Fischer projections.

• If the amino group is on the left, the amino acid is L.

• If the amino group is on the right, the amino acid is D.

Ionization and Zwitterions

Amino acids can exist in different ionization states depending on pH. At physiological pH (~7.4), amino acids are typically zwitterions, carrying both positive and negative charges.

• Zwitterion: A molecule with both a positively charged amino group (–NH3+) and a negatively charged carboxyl group (–COO–).

• Ionization state changes with pH, affecting the overall charge.

Functional Groups of Amino Acids

The side chains (R groups) of amino acids determine their chemical properties and classification.

• Functional groups include alcohols, thiols, carboxylic acids, amides, and various basic groups.

• Side chains vary in size, shape, charge, hydrophobicity, and chemical reactivity.

Classification of Amino Acids by R Group

Amino acids are grouped based on the properties of their side chains:

• Hydrophobic (nonpolar): Side chains are mainly hydrocarbons; tend to cluster away from water (hydrophobic effect).

• Polar (uncharged): Side chains contain groups like hydroxyl or amide; can form hydrogen bonds.

• Positively charged (basic): Side chains terminate with groups that are positively charged at physiological pH (e.g., lysine, arginine).

• Negatively charged (acidic): Side chains terminate with groups that are negatively charged at physiological pH (e.g., aspartate, glutamate).

Examples of Amino Acid Types

• Hydrophobic: Glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline.

• Polar: Serine, threonine, tyrosine, asparagine, glutamine, cysteine, histidine.

• Positively charged: Lysine, arginine.

• Negatively charged: Aspartate, glutamate.

Acid-Base Properties and Titration

Amino acids have ionizable groups that can donate or accept protons, affecting their charge at different pH values.

• Acid-base titration: Used to determine the pKa values of amino acid functional groups.

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

Example: Titration of Glycine

• Three inflection points corresponding to the pKa values of the carboxyl group (2.34), amino group (9.60), and the isoelectric point (5.97).

Example: Titration of Histidine

• Four inflection points: 1.82 (carboxyl), 6.00 (imidazole), 7.59, and 9.17 (amino group).

Modified and Rare Amino Acids

Some amino acids are modified after protein synthesis or are rare exceptions to the standard set of 20.

• Modified amino acids: Covalent modifications such as phosphorylation or hydroxylation.

• Rare amino acids: Selenocysteine (the 21st amino acid), pyrrolysine.

Clinical Insight: Importance of Amino Acids

Amino acids are vital for health. Deficiency can lead to diseases such as kwashiorkor, characterized by edema and immune dysfunction due to insufficient protein intake.

• Kwashiorkor: Disease caused by protein malnutrition, leading to swelling and developmental issues.

Laboratory Techniques: Isoelectric Point and Electrophoresis

Isoelectric focusing and gel electrophoresis are used to separate proteins based on their isoelectric points (pI).

• Isoelectric focusing: Proteins migrate in a pH gradient until they reach their pI.

• Two-dimensional gel electrophoresis: Separates proteins by both pI and molecular weight.

Summary Table: Amino Acid Classification

Key Equations

• Isoelectric Point (pI):

  • For amino acids with two ionizable groups:

• Zwitterion formation:

Test Yourself

• Calculate the isoelectric point (pI) of cysteine.

• Calculate the pI of the peptide AYD-G.

Additional info: These notes expand on the original content by providing definitions, examples, and context for each major concept, ensuring a comprehensive and self-contained study guide for biochemistry students.