Although enzymes speed up reactions, they cannot by themselves force energetically unfavorable reactions to occur. In terms of a water analogy, enzymes by themselves cannot make water run uphill. Cells, however, must do just that in order to grow and divide: they must build highly ordered and energy-rich molecules from small and simple ones. We shall see that this is done through enzymes that directly couple energetically favorable reactions, which release energy and produce heat, to energetically unfavorable reactions, which produce biological order.
What do cell biologists mean by the term “energetically favorable,” and how can this be quantified? According to the second law of thermodynamics the universe tends toward maximum disorder (largest entropy or greatest probability). Thus, a chemical reaction can proceed spontaneously only if it results in a net increase in the disorder of the universe (see Figure 2–16). This disorder of the universe can be expressed most conveniently in terms of the free energy of a system, a concept we touched on earlier.
Free energy, G, is an expression of the energy available to do work—for example, the work of driving chemical reactions. The value of G is of interest only when a system undergoes a change, denoted ∆G (delta G). The change in G is critical because, as explained in Panel 2–7 (pp. 102–103), ∆G is a direct measure of the
Figure 2–27 The structure of the cytoplasm. The drawing is approximately to scale and emphasizes the crowding in the cytoplasm. only the macromolecules are shown: Rnas are shown in blue, ribosomes in green, and proteins in red. enzymes and other macromolecules diffuse relatively slowly in the cytoplasm, in part because they interact with many other macromolecules; small molecules, by contrast, diffuse nearly as rapidly as they do in water (Movie 2.4). (adapted from D.s. Goodsell, Trends Biochem. Sci. 16:203–206, 1991. With permission from elsevier.)
Figure 2–26 a random walk. molecules in solution move in a random fashion as a result of the continual buffeting they receive in collisions with other molecules. This movement allows small molecules to diffuse rapidly from one part of the  cell to another, as described in the text (Movie 2.3).
amount of disorder created in the universe when a reaction takes place. Energetically favorable reactions, by definition, are those that decrease free energy; in other words, they have a negative ∆G and disorder the universe (Figure 2–28).
An example of an energetically favorable reaction on a macroscopic scale is the “reaction” by which a compressed spring relaxes to an expanded state, releasing its stored elastic energy as heat to its surroundings; an example on a microscopic scale is salt dissolving in water. Conversely, energetically unfavorable reactions with a positive ∆G—such as the joining of two amino acids to form a peptide bond—by themselves create order in the universe. Therefore, these reactions can take place only if they are coupled to a second reaction with a negative ∆G so large that the ∆G of the overall process is negative (Figure 2–29).
The Concentration of Reactants influences the free-energy Change and a Reaction’s Direction
As we have just described, a reaction Y ↔ X will go in the direction Y →X when the associated free-energy change, ∆G, is negative, just as a tensed spring left to itself will relax and lose its stored energy to its surroundings as heat. For a chemical reaction, however, ∆G depends not only on the energy stored in each individual molecule, but also on the concentrations of the molecules in the reaction mixture. Remember that ∆G reflects the degree to which a reaction creates a more disordered—in other words, a more probable—state of the universe. Recalling our coin analogy, it is very likely that a coin will flip from a head to a tail orientation if a jiggling box contains 90 heads and 10 tails, but this is a less probable event if the box has 10 heads and 90 tails.