Returning to the whole system, if a spontaneous process is taking place (e.g., MeI hydrolysis), the system is clearly not at equilibrium and so in this sense the term "out of equilibrium" is appropriate. However, this is true of any system that is undergoing a spontaneous change; a nugget of sodium in water is out of equilibrium as is, less excitingly, an ester in alkaline solution. Thus, it is important to specify how the spontaneous process is affecting the properties of the system to decide if it is non-trivially "out of equilibrium", by which we mean that a non-equilibrium steady state can be achieved. Importantly, this also requires us to identify which parts of the system are affected by the coupled reaction; as we show above, reactions that are not directly coupled to the spontaneous process, or part of a cycle in which at least one step is, are not directly affected. Thus, simply saying that a system is "out of equilibrium" does not provide useful information about how the spontaneous process is coupled to the reaction network and if this can lead to a nonequilibrium steady state.