When forming an enzyme-substrate complex in a spontaneous reaction, why does free energy increase?

Question

We eat food and which is digested into proteins and carbohydrates.

Does digestion break bonds within food macro molecules and decreases free energy? Why, when looking at curve, do we see an increase in the free energy and then a decrease?

Answer 1

Kinetics and thermodynamics are two separate things. The type of diagram you show is often encountered (even in textbooks) because it is thought to be a convenient hand-weaving way to convey a feeling of what is happening. However it is not correct as it mixes two different views: the microscopic molecular view (horizontal axis) and the macroscopic thermodynamic view (vertical axis).

The result is a misleading idea that the (molar?) Gibbs free energy (of what ???) can go up (event temporarily) along a spontaneous reaction. However for a spontaneous process (and "spontaneous" is key here) the Gibbs free energy of a system can never increase.

What can increase is the potential energy of a molecular system of the reacting molecules along a reaction path, which is what the vertical axis should represent. In which case the graph would represent a potential-energy profile. But defining a thermodynamic property like a molar Gibbs free energy for a single molecular entity has no meaning.

One might argue that considered as a chemical species, the transition state at the top of the curve (generally called the "activated complex") is obviously unstable and, considered collectively (i.e. macroscopically) must have a higher molar Gibbs free energy (at any specific time during the reaction). However, this is only partially true: it has a higher molar Gibbs free than the product towards which the flux of matter goes, but it necessarily has a lower molar Gibbs free energy than the reactants that are consumed (else the reactants would never form the said activated complex). Also, at the end of the reaction, when equilibrium is reached, all species have equal molar Gibbs free energy so that the Gibbs free energy of reaction is null ($\Delta_r G = 0$).

An alternative, really thermodynamic diagram is sometimes represented: the Gibbs energy diagram. In such diagram, the Gibbs energy of the successive species might appear to go up and down. But one should be careful of the impression given because such diagrams actually represent the standard Gibbs energies of the reactants, which is not their Gibbs free energy in any arbitrary state, and especially not necessarily their Gibbs free energy in the condition of the reaction considered.