Notes on Enzymes

Introduction to Enzymes

What Are Enzymes?

• Definition: Enzymes are biological catalysts that increase the rate of chemical reactions in living cells without undergoing any overall change themselves.
• Substrates: The reactants in enzyme-catalyzed reactions are called substrates.
• Specificity: Each enzyme acts on a specific substrate(s) to produce specific products.
• Nature of Enzymes: All enzymes are proteins but often require a non-protein component to be active.
  • Apoenzyme: Inactive protein component of an enzyme.
  • Holoenzyme: Active enzyme, which includes the cofactor.
  • Cofactors: Can be organic molecules (coenzymes) or metal ions. Strongly bound cofactors are termed prosthetic groups.

A Brief History of Enzymes

• Early Beliefs: Until the 19th century, biological processes (e.g., fermentation, milk souring) were thought to require living organisms.
• Key Discoveries:
  • 1833: Diastase (amylase) discovered, breaking down sugar.
  • Pepsin extracted from gastric juice for protein digestion.
• Evolution of Terms:
  • Originally called ferments; later replaced by the term enzyme proposed by Wilhelm Kühne in 1878 (from Greek "enzume").
• Pioneering Experiments: Eduard and Hans Buchner (1897) demonstrated fermentation of sugar using yeast extracts without living cells.
• Crystallization: James Sumner crystallized urease in 1926, leading to further enzyme purification and study.

Naming and Classification of Enzymes

Why Classify Enzymes?

• Traditional naming often ends with "-ase" (except proteolytic enzymes ending with "-in").
• Example: Lactase hydrolyzes lactose into glucose and galactose:
  $ext{lactose} o ext{glucose} + ext{galactose}$
• Some names indicate substrates/activities, e.g., fumarase does not catalyze hydrolysis but hydration of fumarate to malate.

The Enzyme Commission's System of Classification

• The International Union of Biochemistry (IUBMB) classified enzymes into six main classes based on the reactions they catalyze, assigning a unique code number for each.

Enzyme Classes:

1. Oxidoreductases: Catalyze oxidation/reduction reactions.
2. Transferases: Transfer groups between molecules.
3. Hydrolases: Catalyze hydrolysis reactions.
4. Lyases: Catalyze non-hydrolytic removal of groups, creating double bonds.
5. Isomerases: Catalyze isomerization reactions.
6. Ligases: Synthesize new bonds, often involving ATP.

Enzyme Classification Codes

• Code Structure: Each enzyme has a four-digit code.
  • First digit: Class of enzyme (1-6 as detailed above).
  • Second and third digits: Describe the type of reaction.
  • Fourth digit: Identifies the specific substrate.
• Examples:
  • Lactate dehydrogenase: E.C. 1.1.1.27.
  • Hexokinase: E.C. 2.7.1.1.

Recommendations on Nomenclature

• Systematic naming includes complete substrate names ending with "-ase" (e.g., fumarate hydratase instead of fumarase).
• Trivial names can be used once systematic names are introduced.
• Example of systematic naming includes combinations for reactions involving multiple changes (e.g., oxidoreductase (decarboxylating)).

Summary of Chapter 1

• Enzymes are highly specific proteins that catalyze reactions in living cells and require cofactors to be active.
• The understanding of enzymes has developed, revealing their complex nature and significant role in research and industry.
• The Enzyme Commission has provided systematic names and classifications for enzymes to standardize terminology and avoid confusion.