1694966423_781__lecture_7_Sept17_2023
Page 1: Introduction to Enzymes and Catalysis
Enzymes: Biological catalysts that speed up chemical reactions in organisms.
Catalysis: The process by which enzymes increase the rate of reactions without being consumed.
Required reading: Chapter 7, pp. 323-334.
Page 2: Energy Transformations
Thermodynamics vs. Kinetics: Understand the difference between energy (thermodynamics) and speed (kinetics).
A large negative ∆G indicates spontaneous reactions but not necessarily rapid ones.
Example: Diamond (C) converts to graphite (C) with
∆G = -2.88 kJ/mol, indicating spontaneity, but the process is slow.
Thermodynamic studies reveal free energy differences but do not explain reaction rates.
Page 3: Function of Enzymes
Enzymes increase reaction rates dramatically (by factors of 10^6 or more).
Enzymes lower the activation energy of reactions, making them proceed faster.
Characteristics of enzymes:
Highly specific to substrates and types of reactions.
Do not drive reactions; they help reach equilibrium faster.
Not consumed in reactions; they act as catalysts.
Most enzymes are proteins, with the exception of ribozymes (catalytic RNAs).
Page 4: Key Aspects of Enzymes
Three main aspects of enzyme activity:
High affinity and specificity for substrates.
Binding induces structural changes in the enzyme.
Enzyme activity is regulated in cells.
Page 5: Equilibrium with and without Enzymes
Equilibrium is the same regardless of enzyme presence but is reached quicker with enzymes.
Most biological reactions are slow without enzymes.
Page 6: Turnover Rate of Enzymes
Enzymes can accelerate reactions by a factor of 10^5 to 10^17.
Turnover rate: Number of substrate molecules converted to product per enzyme molecule per second.
Page 7: Transition State and Activation Energy
All chemical reactions pass through a high-energy transition state (S‡).
DG‡: Gibbs free energy of activation – difference in free energy between the transition state and substrate.
Enzymes stabilize the transition state, lowering activation energy (DG‡), hence increasing reaction rate.
Diagram of flow: substrate (S) → transition state (S‡) → product (P).
Page 8: Enzyme-Substrate Interaction Models
Two theories for enzyme-substrate recognition:
Lock-and-Key Hypothesis: Substrate fits perfectly into the enzyme's active site (Emil Fischer).
Induced Fit Model: Both the enzyme and substrate undergo conformational changes to fit together (Daniel Koshland).
The enzyme's active site is most complementary to the transition state structure of the substrate.
Page 9: Interaction Dynamics
Enzyme-induced conformational changes facilitate substrate binding and enhance reactivity.
Example: Enzyme complexes involving active site residues that interact with substrate.
Page 10: Active Site Blocking and Phosphorylation
Conformational changes may block substrates like glucose from the active site, promoting phosphorylation.
Illustration of free vs. bound hexokinase model.
Page 11: Structural Change upon Substrate Binding
Example: Adenylate kinase transitions from unbound to bound with substrate analog.
Importance of structural changes when substrates bind to the enzyme.
Page 12: Energy Profiles of Catalysis
Catalysts lower the activation energy required to reach the transition state G+.
Reaction coordinate diagram shows differences between uncatalyzed and catalyzed reactions.
Page 13: Role of Cofactors in Catalysis
Cofactors: Non-protein compounds aiding enzyme activity, essential for many enzymes.
Types include inorganic ions and organic coenzymes.
~30% of enzymes require cofactors.
Page 14: Example of Cofactors in Action
Example of a copper ion (Cu2+) held in an optimal position by histidine residues for enzyme activity.
Page 15: Coenzymes and Prosthetic Groups
Coenzymes: Small organic molecules required for enzyme function, cannot catalyze reactions alone.
Prosthetic groups: Tightly bound coenzymes, e.g., heme in hemoglobin.
Page 16: NAD+ and NADH Examples
Chemical structures of NAD+ (oxidized) and NADH (reduced) showing enzymatic involvement.
Page 17: Strategies for Enzyme Catalysis
Enzymes may bring substrates into close proximity with correct orientation to facilitate reactions.
Page 18: Key Concepts to Understand
Gibbs Free Energy Equation: DG = DH - TDS.
Importance of enthalpy and entropy changes on DG.
Understand effects of temperature on DG.
Significance of negative/positive DG values, the influence of concentrations on DG, and how unfavorable reactions can occur due to low product concentrations.
Influence of enzyme interactions with substrates on reactions.