4.2 Biochemical catalysis- thermodynamics

To determine if a reaction can take place spontaneously, several key factors must be considered:

Nature of the Reactants: The inherent properties of the reactants, such as their energy states and bonding arrangements, can influence whether they will react spontaneously when mixed.
Equilibrium Position: This refers to whether the equilibrium position favors substrates or products. A reaction at equilibrium will not favor one side, while a reaction that favors products will be more likely to proceed spontaneously.
Actual Concentrations of Reactants: In biological systems, the concentration of reactants often deviates from standard conditions, which impacts the spontaneity of reactions.

Denoted as ∆G°, the standard free energy change is relevant under specific standard conditions:

Temperature: 25°C (298 K)
Pressure: 1 atm
Concentration: 1 molar concentrations of reactants (often at pH 7 in biochemical contexts)

Purpose and Utility:

Provides a constant for given reactions, facilitating comparison between different reactions.
Relates to the equilibrium constant (K_eq), offering insights into the ratio of substrates to products.
Indicates the direction of spontaneity; if ∆G° is negative, the reaction favors product formation under standard conditions.

The equilibrium constant, K_eq, represents the ratio of products to substrates at equilibrium and can be expressed mathematically:

The relationship is given through the equation: ∆G° = -RT ln(K_eq)
- Where R is the gas constant (8.314 J/(mol K)) and T is the temperature in Kelvin.

Interpretation of K_eq:

K_eq < 1: This indicates a positive ∆G°, suggesting that the equilibrium favors the substrates.
K_eq > 1: This implies a negative ∆G°, indicating that the equilibrium favors the products.
Example: If K_eq is 10, the resulting ∆G°= -5.7 kJ/mol signifies that the reaction proceeds favorably towards products.

In vivo, reactants rarely exist at 1 molar concentrations; thus, the actual concentrations must be considered when assessing free energy changes.

The reaction quotient (Q) is employed to account for current concentrations relative to equilibrium, affecting the spontaneity of the reaction.

Some thermodynamically unfavorable reactions can be coupled with favorable ones to drive the overall process forward.

Example: In glycolysis, the phosphorylation of glucose (unfavorable with ∆G° of +13.8 kJ/mol) is coupled with the hydrolysis of ATP (favorable with ∆G° of -30.5 kJ/mol).
The combined ΔG° for the coupled reaction becomes -16.7 kJ/mol, indicating a thermodynamically favorable process, crucial for cellular metabolism.

It is essential to distinguish between thermodynamic favorability and kinetic speed:

A thermodynamically favorable reaction does not guarantee that it will occur rapidly.
The rate of reaction is defined by the speed at which products are formed or substrates are consumed over time.
Activation Energy (Ea): This is the initial energy input required to initiate a reaction. High activation energies can slow down reactions considerably, even if the overall free energy change is favorable.
Collision Theory: The rates are influenced by the frequency and effectiveness of collisions between reactant molecules. Successful collisions must occur with the proper orientation to facilitate the reaction.

This concept represents the energy distribution of reactant molecules in a system. The shaded area in the graph signifies the proportion of molecules that have sufficient energy to surpass the activation energy barrier required for the reaction.
Increasing temperature enhances molecular motion, thereby increasing the average kinetic energy and the likelihood of successful collisions, ultimately raising the reaction rates.

Catalysts, including enzymes, accelerate reactions through the provision of alternative pathways with lower energy barriers (reduced activation energy).
Enzymes also enhance the orientation of substrates, further facilitating the transition to products.

Spontaneity vs. Reaction Rate: ∆G° indicates whether a reaction is spontaneous; however, it does not provide information about the reaction rate.
Activation Energy Necessity: High activation energy can lead to slow reaction rates.
Enzymatic Role: Enzymes reduce activation energy but do not alter the overall free energy change of the reaction, essential for processes like ATP synthesis in cells.