Enzyme Kinetics and Thermodynamics

Enzyme Kinetics vs. Thermodynamics

• Catalysis is a critical function of proteins that is essential for efficient metabolism, without which biological reactions would proceed too slowly
• Enzymes are biological catalysts that significantly accelerate reactions.
• Most enzymes are globular proteins, except for ribozymes, which are catalytic RNAs
• Enzymes can increase reaction rates by up to 10^20 times compared to uncatalyzed reactions.
• Nonenzymatic catalysts enhance reaction rates by 10^2 to 10^4 times.
• Enzymes exhibit high specificity and can differentiate between stereoisomers of the same compound
• Enzyme activity is regulated for precise control over reactions.

Key Terms

• Catalysis increases the rate of chemical reactions
• Enzymes are biological catalysts, typically globular proteins, except for self-splicing RNA.
• Standard free energy change is the energy difference between reactants and products under standard conditions.
• Activation energy is the minimum energy required to start a reaction
• Transition state is the intermediate stage where old bonds break and new ones form.
• Substrate is a reactant in an enzyme-catalyzed reaction
• Active site is the specific part of an enzyme where the substrate binds and the reaction occurs

Standard Free Energy Change (ΔG°)

• ΔG° represents the energy difference between reactants (initial state) and products (final state)
• ΔG° predicts reaction spontaneity, based on thermodynamics
  • Negative ΔG° indicates a spontaneous reaction that proceeds without external energy
  • Positive ΔG° indicates a non-spontaneous reaction requiring energy input
  • ΔG° = 0 indicates the system is at equilibrium with no net change
• A negative ΔG° signifies that the reaction releases energy and is thermodynamically favorable.

Thermodynamic Principles

• Reaction rate and thermodynamic favorability are distinct but related concepts
• Thermodynamic principles apply to all reactions, regardless of catalyst presence
• The standard free energy change (ΔG°) represents the energy difference between reactants and products, indicating thermodynamic favorability
• Enzymes, increase reaction rates without changing the equilibrium constant or free energy change
• Reaction rate is influenced by the activation energy (ΔG‡), the energy required to initiate a reaction

Activation Energy

• Uncatalyzed reactions have higher activation energy compared to catalyzed reactions, resulting in slower rates
• The reaction of glucose with oxygen to produce carbon dioxide and water requires several enzymatic catalysts, shown by the formula: Glucose + 6O2 → 6CO2 + 6H2O
  • This reaction is thermodynamically favorable with a negative free energy change (ΔG° = -2880 kJ/mol or -689 kcal/mol)
• Spontaneous reactions occur without external energy input but may not be quick.
• Activation energy is the energy needed to start a reaction
• Activation energy can be graphically represented, with the x-axis showing reaction progress and the y-axis showing free energy
• The highest point on the curve is the transition state, where reactants have enough energy to form products
• Catalysts lower activation energy, which speeds up reactions.
• Glucose oxidation is a spontaneous reaction with high activation energy
• Enzymes reduce this energy, speeding up the reactions
• Catalysts lower the activation energy, increasing the reaction rate without changing the overall energy change (ΔG°)

Enzyme-Substrate Complex

• In enzyme-catalyzed reactions, the enzyme binds to a substrate (reactant), forming a complex that leads to product formation
• The active site is a small area made up of specific amino acids where the substrate binds, typically through noncovalent interactions.

Enzyme-Substrate Complex Models

• In the Lock-and-Key Model, the substrate and enzyme have complementary shapes that fit together like a key in a lock
• In the Induced-Fit Model, the enzyme changes shape upon substrate binding for a better fit, allowing catalysis to occur.
• The induced-fit model supports better theory as it mimics the transition state.

Coenzymes

• Coenzymes are small, non-protein molecules that work with enzymes to speed up biochemical reactions
• They are critical for various biochemical reactions and assist enzymes in their catalytic activity
• Coenzymes can be reused multiple times in different reactions

Cofactors and Coenzymes

• Cofactors are essential for enzymatic reactions, and include essential ions, coenzymes, and prosthetic groups that contribute to enzymes’ overall functionality
• Cofactors are divided into:
  • Essential Ions: Necessary for enzyme function, categorized into:
  • Activator Metal Ions: Loosely bound to the enzyme
  • Metal Ions of Metalloenzymes: Tightly bound to the enzyme
  • Coenzymes: Organic molecules that assist enzymes and are loosely bound
  • Prosthetic Groups: Organic molecules tightly bound to the enzyme.

Metal Ions in Coenzymes

• Metal ions are Lewis acids that accept electron pairs in coenzymes.
• They form coordination compounds by binding with groups that behave as Lewis bases and are essential in metal ion function within biological systems
• Zinc (Zn(II)) in carboxypeptidase and iron (Fe(II)) in hemoglobin are examples of their use.
• The geometric arrangement of metal ions in these compounds is vital for positioning reactant groups and enhancing catalytic efficiency

Organic Coenzymes

• Organic coenzymes, especially those derived from B vitamins, are crucial for biological functions
• These coenzymes play roles in oxidation-reduction reactions to generate metabolic energy for cellular activities
• They are involved in group-transfer reactions
• These reactions are vital in metabolic pathways, facilitating the transfer of functional groups between molecules
• This is essential for synthesizing and breaking down biomolecules, converting nutrients into energy
• B vitamin-related coenzymes are indispensable in maintaining metabolic functions and energy production.