There is no more important conceptual underpinning from physical science for biochemistry than Gibbs free energy change. To understand the meaning of free energy change, you have to first understand the Carnot cycle, the simple model of a reversible engine that demonstrates the difference between spontaneity and equilibrium and how work can be performed when heat flows are moving from high to low temperature. You need both the first and second laws of thermodynamics in your analytical toolkit to understand the Carnot cycle. Each stage of the Carnot cycle should be assessed in terms of both laws.
The first law of thermodynamics allows us to describe each step in terms of heat flow, work performed, and internal energy change. The second law enables us to discuss how the changes in entropy in the system and surroundings are balancing out at every stage. Every stage of the Carnot cycle is microscopically reversible, and the entropy of the universe does not increase.
However, heat still must be expelled at the cold sink, even though entropy is not increasing. Otherwise, entropy in the universe would actually decrease
. By being reversible, the Carnot cycle finds the limit of heat that can be turned into work without decreasing the entropy of the universe. In this sense, the Carnot cycle represents the ideal (most efficient) thermodynamic cycle possible. Compared to the Carnot cycle, all real cycles would result in even more heat being lost to the cold sink for a given amount of work.