Biochemical reactions are characterized by a Gibbs free energy change that describes the amount of energy produced or consumed in the reaction. In order to compare different reactions, chemists have developed a standard Gibbs free energy change that can be used to describe all reactions. The standard Gibbs free energy change in biochemical reactions is the energy produced or consumed when all the reactions and products are at a concentration of 1M, the temperature is 25°C (298 K), the pressure is 1 atm, the pH is 7.0, and the concentration of water is 55M.
Here's an example from the gluconeogenesis/glycolysis pathway (see below). It's the reaction catalyzed by aldolase where a six-carbon molecule (fructose) is cleaved to produce two three-carbon molecules. The reaction shown here is the one in the glycolysis pathway that breaks down glucose.
The standard Gibbs free energy change for this reaction is ...
In a chemistry course you might learn that this reaction is NOT spontaneous because the standard Gibbs free energy change is positive. In other words, you need to supply energy—as indicated by the plus sign in the standard Gibbs free energy change—in order to make the reaction go from left to right. The reaction will be "spontaneous" in the opposite direction where ΔG'°reaction = -28 kJ mol-1.
The concept of "spontaneous" and "not spontaneous" based on the standard Gibbs free energy change make no sense in a biochemical context. The aldolase reaction, for example is part of the gluconeogenesis pathway where the two three-carbon molecles are joined to produce fructose-1,6-bisphosphate. This eventually leads to the production of glucose.
The adolase reaction is also part of the glycolysis pathway that runs in the opposite direction (as shown above). Cells can easily switch from making glucose to degrading it. How can this happen if the free energy change is +28 kJ mol-1.1
It isn't. The actual Gibbs free energy change inside the cell is very different than the standard Gibbs free energy change. This reaction rapidly reaches equilibrium inside the cell. Under those conditions the rates of the forward and reverse reactions are equal and ΔG = 0.
In the case of the aldolase reaction, the concentrations of the reactants and products at equilibrium will not be equal as the standard Gibbs free energy change requires. Instead, the concentration of fructose-1,6-bisphosphate will be much higher than the concentrations of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
In biochemical terms we say that this is a "near-equilibrium" reaction. Most metabolic reactions are near-equilibrium reaction with ΔG = 0 (or close to it).
This is an important concept in biochemistry. You can't understand pathways and flux if you don't know that most of the reactions are near-equilibrium reactions where ΔG = 0.Sup>1 You also can't understand regulated reactions, where ΔG is not zero, unless you've grasped the fundamentals. (Regulated reactions are called "metabolically irreversible reactions.")
Many textbooks do a poor job of explaining near-equilibrium reactions and their importance in metabolic pathways. Some still use standard Gibbs free energy changes as a measure of direction. Fortunately, the teaching of this concept has improved enormously over the past 15 years.3 The bad news is that if you took your last biochemistry course before 1995 you may be hopelessly out-of-date!
Here's an example of bad teaching from a 2003 textbook!
Although the cleavage of fructose-1,6-bisphosphate is frequently unfavorable (ΔG'° = +23.8 kJ/mol), the reaction proceeds because the products are rapidly removed.
1. You also have to understand the concept of steady-state—the concentrations of intermediates in a pathway don't change very much.
2. Some textbooks use +24 kJ mol-1.
3. The best textbooks had it right long before that.