Medical Enzymology Overview

Medical Enzymology

• Enzymes are biological catalysts that increase the rate of chemical reactions.
• Enzymes are mostly proteins, but some are RNA (ribozymes).
• Enzymes are required in small amounts and remain unchanged during reactions.
• All biological functions in living tissues rely on chemical reactions.
• Reactions proceed at 37°C (body temperature) because of enzymes.
• Almost all reactions in living tissues are catalyzed by enzymes.

Intended Learning Outcomes (ILOs)

• Define enzymes, identify enzyme nomenclature, classes, and commission code.
• Identify enzyme-related terms (apoenzyme, holoenzyme, coenzyme, prosthetic group, cofactor).
• Discuss enzyme properties (specificity, catalytic efficiency, subcellular localization, active site, catalytic sites).
• Describe the mechanism of enzyme action (catalysis).

What are Enzymes?

• Enzymes are biological catalysts, increasing the rate of chemical reactions.
• Mostly proteins, with RNA exceptions (like peptidyl transferase).
• Enzymes are needed in small amounts.
• Enzymes are unchanged during reactions.

Why are Enzymes Important?

• Enzyme-mediated chemical reactions are crucial for all living tissue functions.
• Car engines use combustion reactions; our cells use enzymes for similar functions at a much lower temperature.
• Nearly all reactions in living tissues are catalyzed by enzymes.

Enzyme Nomenclature

• Two naming systems exist.
• Common names: the suffix "-ase" is appended to the substrate name (e.g., Urease, Glucosidase). Names might also describe the enzyme's action (e.g., lactate dehydrogenase).
• Systematic names: use the whole chemical reaction’s description in the name, including all substrates. They're long and less common, e.g., lactate:NAD+ oxidoreductase = lactate dehydrogenase.

Classes of Enzymes

• Enzymes are categorized based on their function.
• Oxidoreductases: handle oxidation-reduction reactions. (Example: lactate dehydrogenase)
• Transferases: transfer specific groups between molecules. (Example: aminotransferase)
• Hydrolases: use water to break bonds. (Example: Lipases)
• Lyases: add/remove groups to/from molecules, forming or breaking double bonds. (Example: Aldolase A)
• Isomerases: convert molecules into isomers. (Example: Triose phosphate isomerase)
• Ligases: join molecules using energy (ATP). (Example: Fatty acyl CoA synthetase)

Enzyme Commission Code (EC code)

• Enzyme-related reactions can be specified through EC numbers (assigned by IUBMB).
• These codes have four numbers separated by dots.
• The first number indicates the enzyme class (e.g., 2 = transferase).

Holoenzyme and Apoenzyme

• Apoenzyme: the protein part of an enzyme.
• Holoenzyme: the complete, active enzyme (apoenzyme + non-protein part).

Non-protein parts (Cofactors)

• Cofactors: non-protein components enabling enzyme function.
• Coenzymes: tightly bound, often containing vitamins. (Example: TPP, FMN, FAD)
• Prosthetic groups: tightly bound cofactors. (Example: Biotin)
• Metal ions: loosely or tightly bound metal atoms involved in enzyme action.
• Metalloenzymes: enzymes containing tightly bound metal ions. (Example: Fe in peroxidases)

Enzyme Specificity

• Enzymes usually interact with only one or a few specific substrates.
• Specificity can be based on molecule shape/structure (e.g., isomers, certain types of bonds).
• Some enzymes specifically interact with hydrogen carriers (e.g. NAD+ or FAD). Examples include L-amino acid oxidases that show specificity to L amino acids not D amino acids.

Subcellular Localization

• Many enzymes are located in specific cellular compartments.
• This localization creates optimal conditions for reactions.
• Examples include glycolysis in the cytosol and the Krebs cycle primarily in mitochondria.

Catalytic Efficiency

• Enzymes significantly boost reaction rates compared to un-catalyzed reactions.
• Turnover number (kcat): The speed rate enzyme works , it's how many substrate molecules an enzyme molecule can convert into a product in a given time. (Typically 10² - 10⁴ molecules per second).

Mechanism of Enzyme Action

• Enzymes lower the activation energy needed for a reaction but don't alter the overall reaction's energy changes.
• Active site: Crucial site where substrates bind and reactions occur.

Energy Changes During the Reaction

• Activation energy: The energy needed to start a chemical reaction.
• Transition state: The unstable intermediate step in a reaction.
• Enzyme-catalyzed reactions proceed rapidly because they lower the reaction’s activation energy.
• Enzymes do not change the overall free energy of a reaction ( only the activation energy).

Active Sites Facilitate Catalysis

• Active sites stabilize transition states, which helps products form.
• Catalytic groups at the site can support specific steps in the reaction.

References for Further Readings

• Lippincott Illustrated Review Integrated system 3rd edition
• Lippincott Illustrated Review 6th edition
• Oxford Hand book of Medical Science 2nd edition