Enzyme catalysis and the transition state

What is happening in a chemical reaction

Input of heat energy (enthalpy) -> output heat energy (enthalpy)

The overall reactions can be:

• Exothermic: outputs energy (heat)

• Endothermic: takes in energy (heat)

This is described by the change in the term enthalpy (∆H)

• Exothermic: -∆H

• Endothermic: +∆H

entropy

the heat energy is distributed more uniformly across the system - less order

The arrangement of molecules and their associated energy changes through the reaction

Is a chemical reaction feasible

Thermodynamic potential energy is defined by Gibbs free energy. 

Defining the change in Gibbs free energy for a chemical reaction allows us to identify whether reactions are spontaneous - change is negative 

Thermodynamics 

Gibbs free energy (G) is a measure of usable energy in a system for work 

What do enzymes do to a reaction

Enzymes stabilise the transition state to accelerate the reaction - reduce the energy of activation for the reaction

Enzymes accelerate reaction rates to reach equilibrium but are unable to change the overall equilibrium position

How do enzymes stabilise the transition state

enzymes are thought to form favourable interactions with the transition state to reduce the activation energy for catalysis 

What occurs in a reversible reaction

change in Gibbs is related to the equilibrium constant

glycolysis 

enzymatic pathways can combine favourable and unfavourable reactions to drive chemistry of primary and secondary metabolites 

reaction pathways often utilise cofactors like ATP and NADPH to drive biosynthesis of primary and secondary metabolites 

coupling reactions within larger pathways (metabolism)

ATP hydrolysis is an exergonic reaction which is widely used in biochemical reactions to drive biosynthesis

effects of temperature on enzyme catalysis

raising the temperature increases reaction rate

• higher temperature: more kinetic energy for catalysis and reactions occur more frequently 

at a certain temperature the enzyme begins to denature and activity decreases 

the pH profiles vary from enzyme to enzyme depends on

• Charge state of enzyme and/or substrate 

• Enzyme stability, denaturing often occurs at extreme pH

ionisable groups

pH alters the charges of ionisable group on the protein surface and in the active site impacting substrate binding and enzyme stability