Enzymes and Reactions

Reactions Coupled with ATP Hydrolysis

• Reactions with a positive free energy change ($\Delta G$) will not occur spontaneously.
• Reactions coupled with ATP hydrolysis must have an overall negative $\Delta G$ to occur.
  • Example: Reaction 5 (E + Pi -> Ep) has a $\Delta G$ of +5 kcal/mol. When coupled with ATP hydrolysis, the overall $\Delta G$ becomes -2.3 kcal/mol, making the reaction possible.

Laws of Thermodynamics and Reaction Rate

• Laws of thermodynamics indicate whether a reaction can occur spontaneously (based on $\Delta G$) but do not determine the reaction rate.

Enzymes and Catalysis

• Enzymes (catalytic proteins) speed up metabolic reactions by lowering the activation energy barrier.
• Biological catalyst: A chemical agent that speeds up a reaction/alters the reaction without being consumed in the process.
• Without enzymes, reactions would be very slow.

Activation Energy

• $E_a$ is the initial energy needed to start a chemical reaction.
• Reactions involve breaking/forming bonds, requiring reactants to absorb energy to reach an unstable transition state.
• Enzymes lower the $E_a$, allowing a larger fraction of molecules to react and increasing the reaction rate.
• Catalysts reduces the energy required to reach the transition state but do not affect the free energy change ($\Delta G$).

Enzyme Specificity

• Enzymes are specific to particular reactions due to the shape of their active sites.
• Most enzymes can catalyze both forward and reverse reactions, depending on which direction has a negative free energy change.

Catalytic Cycle of Enzymes

• Enzymes bind substrates at their active sites, forming an enzyme-substrate complex.
• Induced fit model: Enzyme changes shape upon substrate binding.
• The enzyme-substrate complex lowers the activation energy, speeding up the reaction.
• Substrates are converted to products and released, and the enzyme remains available for further reactions.
• Enzymes are not consumed in the reactions they catalyze.

Regulation of Metabolic Pathways

• Cells regulate metabolic pathways by controlling enzyme activity via:
  • Switching enzymes on/off.
  • Regulating genes that encode specific enzymes.

Allosteric Regulation

• Allosteric regulation: A protein's function at one site is affected by the binding of a regulatory molecule at another site.
• Enzymes oscillate between active and inactive forms.
  • Activators stabilize the active form.
  • Inhibitors stabilize the inactive form.

Feedback Inhibition

• The product of a metabolic pathway inhibits the pathway.
  • Example: Isoleucine inhibits threonine deaminase, the enzyme that converts threonine to an intermediate in isoleucine synthesis.

Factors Affecting Enzyme Activity

• Temperature and pH: Enzymes have optimal conditions for maximal activity.
  • Human enzymes: Optimal temperature is 37°C.
  • Pepsin (stomach): Optimal pH is 2 (acidic).
  • Trypsin (intestines): Optimal pH is 8 (alkaline).
• Cofactors: Inorganic molecules (metal ions) or organic molecules (coenzymes) that influence enzyme activity.