Detailed Notes on Enzymes and Catalysis

Enzymes: Biological Catalysts
  • Enzymes are proteins that act as biological catalysts. Some enzymes are RNA.
  • Substrate: The specific substance that an enzyme acts on.
  • Catalysts:
    • Increase the rate of a chemical reaction by lowering the activation energy needed to reach the transition state.
    • Enzymes are not consumed or changed in the reaction process.
    • They do not affect the thermodynamics of the reaction, i.e., do not change the position of equilibrium or free energy difference.
    • Enzymes confer kinetic control, allowing cells to regulate the speed of metabolic reactions.
Specific Characteristics of Enzymes
  • Enzymes catalyze stereo-selective biochemical reactions, typically favoring only one stereoisomer.
  • Specificity: The selectivity of an enzyme for its substrate.
  • Catalytic power: Ratio of enzyme-catalyzed reaction rate to that of the uncatalyzed rate.
  • Enzyme activity is regulated to match the metabolic needs of the cell.
  • Enzymes are sensitive to temperature and pH, requiring specific ranges for optimal function.
  • A unique 3D structure is necessary for catalytic activity.
Six Major Classes of Enzymes

  1. Oxidoreductases

    • Example: Alcohol dehydrogenase
    • Catalyze redox reactions.

  2. Transferases

    • Example: Hexokinase
    • Transfer functional groups between molecules.

  3. Hydrolases

    • Example: Carboxypeptidase A
    • Catalyze hydrolytic cleavage of bonds.

  4. Lyases

    • Example: Pyruvate decarboxylase
    • Remove or add groups to double bonds.

  5. Isomerases

    • Example: Maleate isomerase
    • Catalyze isomerization processes.

  6. Ligases

    • Example: Pyruvate carboxylase
    • Join two molecules together.
Enzyme Classification and Databases
  • Enzymes have a systematic naming convention with specific substrate and reaction details (E.C. number).
  • Enzyme information can be accessed in databases such as BRENDA, ExPASy, and IUBMB.
Chemical Reaction Rates and Catalysis
  • Reaction rates depend on:
    1. Order of reaction
    2. Concentrations of reactants/products
    3. Temperature
    4. Rate constant
  • The favorability of a reaction is determined by free energy changes; reactions with negative Gibbs free energy will occur spontaneously.
Transition State and Enzyme Function
  • The transition state is a high-energy, unstable species that represents the peak of energy before products form.
  • Enzymes reduce the activation energy needed to reach this state, significantly enhancing reaction rates.
  • Methods of increasing reaction rates:
    1. Increasing temperature: Raises kinetic energy.
    2. Lowering transition state's free energy: Makes it easier for substrates to reach it.
Mechanisms of Catalysis
  • Different mechanisms include:
    • Electrostatic catalysis: Stabilizes transition states with ionic interactions.
    • Covalent catalysis: Alters the reaction pathway by forming temporary covalent bonds.
    • Acid-base catalysis: Involves proton transfer to stabilize charged intermediates.
    • Proximity effects: Enzymes bring substrates closer together to increase the likelihood of reaction.
Examples of Enzymes and Mechanisms
  • Lysozyme: Cleaves bacterial cell walls; its catalytic mechanism involves multiple phases, including the formation of an intermediate state.
  • Chymotrypsin: A serine protease with a catalytic triad that facilitates peptide bond hydrolysis by stabilizing transition states using its structure.
Coenzymes, Vitamins, and Metals
  • Coenzymes are necessary for the function of enzymes, facilitating reactions often related to electron transfer or group transfer. Examples include:
    • Thiamine (B₁) - Coenzyme: Thiamine pyrophosphate
    • Riboflavin (B₂) - Coenzyme: Flavin mononucleotide
    • Vitamin B12 - Coenzyme: Cobalamin
  • Metalloenzymes include metal ions essential for catalytic activity, often serving as cofactors in enzymes.
Enzyme Kinetics
  • Kinetic parameters such as Vmax (maximum reaction velocity) and KM (Michaelis constant) help measure enzyme activity.
  • Vmax occurs when the enzyme is saturated with substrate.
  • The efficiency of an enzyme can be indicated by the ratio kcat/KM, where lower KM indicates better substrate binding.
Enzyme Inhibition
  • Inhibition types:
    1. Competitive: Inhibitor competes with substrate for the active site.
    2. Uncompetitive: Inhibitor binds the enzyme-substrate complex.
    3. Irreversible: Permanently inactivates the enzyme through covalent bonds.
    • Example: Captopril, a competitive inhibitor used to treat hypertension by inhibiting the angiotensin-converting enzyme.
Regulation of Enzyme Activity
  • Enzyme activity is regulated through:
    • Feedback inhibition: End product of a pathway inhibits an upstream process.
    • Allosteric regulation: Conformational changes affecting enzyme activity upon binding of an effector molecule.
    • Covalent modifications: Such as phosphorylation or methylation to alter enzyme function.