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5.5: Coupling Reactions

There are large numbers of different types of reactions that occur within cells. As a rule of thumb, a reaction that produces smaller molecules from larger ones will be thermodynamically favored, while reactions that produce larger molecules from smaller ones will be unfavorable. Similarly a reaction that leads to a molecule moving from a region of higher concentration to a region of lower concentration will be favored. So how exactly can we build the big molecules, such as DNA and proteins, and concentration gradients that life depends upon?

As we noted before reactions can be placed into two groups, those that are thermodynamically favored (negative ΔG, equilibrium constant is greater, typically much greater, than 1) and those that are unfavorable (positive \(ΔG\), equilibrium constant less, often much less than 1). Thermodynamically favored reactions are typically associated with the release of energy from and the breakdown of various forms of food (known generically as catabolism), while reactions that build up biomolecules (known generically as anabolism) are typically thermodynamically unfavorable. An organism’s metabolism is the sum total of all of these various reactions.

Unfavorable reactions occur when they are coupled to thermodynamically favorable reactions. This requires that the two reactions share a common intermediate. In this example the two reactions share the component "D". Let us assume that the upper reaction is unfavorable while the lower reaction is favorable. What happens? Let us assume that both reactions are occurring at measurable rates, perhaps through the mediation of appropriate catalysts, which act to lower the activation energy of a reaction, and that E is present within the system. At the start of our analysis, the concentrations of A and B are high. We can then use Le Chatelier’s principle to make our predictions152.

Let us illustrate how Le Chatelier’s principle works. Assume for the moment that the reaction

\[A + B \rightleftharpoons C + D\]

has reached equilibrium. Now consider what happens to the reaction if, for example, we removed (somehow, do not worry about how) all of the \(C\) from the system. Alternatively, consider what happens if we add more B to the system. The answer is that the reaction moves to the right even though that reaction is thermodynamically unfavorable, in order to re-establish the equilibrium condition. If all C were removed, the C + D to A + B reaction could not occur; the A + B reaction would continue in an unbalanced manner until the level of C (and D) increased and C + D to A + B reaction would balanced the A + B to C + D reaction. In the second case, the addition of B would lead to the increased production of C + D until their concentration reached a point where the C + D to A + B reaction balanced the A + B to C + D reaction. This type of behavior arises directly from the fact that at equilibrium reaction systems are not static, but dynamic (at the molecular level) – things are still occurring, they are just balanced so that no net change occurs. When you add or take something away from the system, it becomes unbalanced, that is, it is no longer at equilibrium. Because the reactions are occurring at a measurable rate, the system will return to equilibrium over time.

So back to our reaction system. As the unfavorable A + B reaction occurs and approaches equilibrium it will produce a small amount of C + D. However, the D + reaction is favorable; it will produce F while at the same time removing D from the system. As D is removed, it influences the A+B reaction (because it makes the C + D "back reaction" less probable even though the A+B "forward reaction" continues.) The result is that more C and D will be produced. Assuming that sufficient amounts of E are present, more D will be removed. The end result is that, even though it is energetically unfavorable, more and more C and D will be produced, while D will be used up to make F. It is the presence of the common component D and its utilization as a reactant in the D + E reaction that drives the synthesis of C from A and B, something that would normally not be expected to occur to any great extent. Imagine then, what happens if C is also a reactant in some other favorable reaction(s)? In this way reactions systems are linked together, and the biological system proceeds to use energy and matter from the outside world to produce the complex molecules needed for its maintenance, growth, and reproduction153.

Questions to answer & to ponder

  • What are the common components of a non-equilibrium system and how does a dried out tardigrad fulfill those requirements?
  • You use friction to ignite a fire. Where does the energy released by the fire come from?
  • A reaction is at equilibrium and we increase the amount of reactant. What happens in terms of the amount of reactant and product?
  • A reaction is at equilibrium and we increase the amount of product. What happens in terms of the amount of reactant and product?
  • What does the addition of a catalyst do to a system already at equilibrium?
  • What does the addition of a catalyst do to a system far from equilibrium?
  • Where does the energy come from to reach the activation state/reaction intermediate?
  • Why does a catalyst not change the equilibrium state of a system?
  • Why are catalysts required for life?


  • Michael W. Klymkowsky (University of Colorado Boulder) and Melanie M. Cooper (Michigan State University) with significant contributions by Emina Begovic & some editorial assistance of Rebecca Klymkowsky.