The form of the network and eq. 1, allow us to make some general observations: i. The relative concentrations of [RCO2Me] and [RCO2] are perturbed from their equilibrium values (i.e., a non-equilibrium steady state is achieved) if the coupled reaction is spontaneous in either direction. ii. Coupling arises practically because the carboxylate anion mediates the hydrolysis of MeI. iii. If, as here, we assume an elementary (SN2) ester hydrolysis mechanism (formally BAl2), there is no net flux between RCO2Me and RCO2 -at steady state, although there is net flux over the two pathways that connect them. If instead hydrolysis proceeds via an intermediate (e.g., BAC2), the equations have the same form (see ESI) but in this case there is net flux between all species in the cycle. 16 This leads to the following general observations: i. The relative concentrations of species within a cycle coupled to a spontaneous process can be perturbed from their equilibrium values and net flux can take place across the different pathways that connect them. ii. The relative concentrations of species not within a coupled cycle are unaffected by the coupled reaction. iii. Based on i. and ii., crudely speaking, the species within the coupled cycle can be "away from equilibrium" but off cycle process must be "at equilibrium"; it is not useful to describe the whole system as "out of equilibrium".