BSC1010 Lecture 8b

Chapter 6: An Introduction to Metabolism

Section B: Enzymes

• Key concepts to master:

  • Activation Energy

  • Free Energy

  • Enzymes and Activation Energy

  • Enzyme Structure

Molecular Interactions

• Not every collision between molecules results in bond formation due to:

  • Correct orbital conformation needed.

  • Existing bonds must be broken first (e.g., CO + NO2 → CO2 + NO).

  • High kinetic energy is necessary to break bonds; low energy leads to mere bouncing.

Chemical Reactions

• Chemical reactions involve:

  • Both bond breaking and forming.

  • Example: Hydrolysis of sucrose requires breaking glucose and fructose bonds, then forming new bonds with water's hydrogen ion and hydroxyl group.

Activation Energy (EA)

• Even in exergonic reactions, reactants must absorb energy called Activation Energy (EA).

  • This is the minimum energy required to break bonds.

  • In exergonic reactions, EA energy is returned to surroundings along with additional energy from new bond formation.

Energy Barriers

• Activation energy is necessary to push reactants over an energy barrier.

• Delta G represents the difference in free energy between products and reactants.

Temperature and Activation Energy

• Some processes have low barriers where room temperature suffices; others require significant input of energy.

• Example: A spark plug energizes gasoline hydrocarbons, enabling reaction with oxygen.

Thermodynamics Limitations

• The laws of thermodynamics suggest breakdown of complex molecules, yet typical cellular temperatures do not provide enough energy for activation.

• Heat would accelerate reactions but risk denaturing proteins, harming cells.

Role of Catalysts

• A catalyst is a chemical agent altering reaction rates without consumption.

• Enzymes, as catalytic proteins, regulate molecular movement through metabolic pathways.

Enzyme Functionality

• Enzymes speed up reactions by lowering EA.

• They do not alter delta G, accelerating processes without changing their natural outcome.

• Enzyme selectivity dictates which processes occur at a given time.

Substrates and Active Sites

• A substrate is the reactant that binds to an enzyme.

• Enzymes convert substrates into products (e.g., sucrase breaks down sucrose).

• The active site is the region on the enzyme where the substrate fits, leading to a tighter induced fit upon binding.

Enzyme Activity

• Substrates bind to active sites via weak interactions (e.g., hydrogen/ionic bonds).

• Enzymes form complexes with substrates to facilitate reactions.

Characteristics of Enzymes

• Enzymes are substrate-specific and catalyze thousands of reactions per second.

• They are unaffected and reusable in reactions.

• Metabolic enzymes can drive reactions in both forward and reverse directions based on product/reactant concentrations.

Mechanisms of Enzyme Function

• Enzymes lower activation energy through:

  • Correct substrate orientation.

  • Inducing stress on bonds that need breaking.

  • Temporary covalent bonding to change substrate shape.

Environmental Influences on Enzymes

• Chemical environment (temperature, pH) impacts enzyme structure and function.

  • **Temperature: ** Affects reaction rates; optimal temperature varies per enzyme.

  • High temperatures can denature proteins.

• pH Levels: Each enzyme has an optimal pH, with most around pH 6-8, while digestive enzymes vary (e.g., stomach enzymes at pH 2).

Cofactors in Enzyme Function

• Many enzymes require cofactors for activity:

  • Inorganic Cofactors: Examples include zinc, iron, copper (bind permanently or reversibly).

  • Organic Cofactors (Coenzymes): Derived from vitamins (e.g., NAD, NADP, FAD).

Enzyme Inhibition and Control

• Competitive Inhibition: Inhibitors bind to active sites, blocking substrate access.

  • Inhibition can be irreversible (covalent bond) or reversible (weak binding).

• Allosteric Site: Non-active site binding can inhibit/stimulate enzyme activity.

• Non-Competitive Inhibition: Inhibitors bind elsewhere, altering the shape of the active site and blocking substrate binding.

Regulation of Metabolic Pathways

• Allosterically regulated enzymes often consist of multiple polypeptide chains, with active and allosteric sites at subunit junctions.

  • Conformational oscillation between active and inactive states.

Feedback Inhibition in Metabolic Control

• Metabolic pathways can be regulated by feedback inhibition, where the final product inhibits an enzyme in the pathway.

  • When product levels are high, the pathway is turned off; when low, it is reactivated.