  Biochemical systems that express certain chemical species of interest at the
same level at any positive equilibrium are called "absolute concentration
robust" (ACR). These species behave in a stable, predictable way, in the sense
that their expression is robust with respect to sudden changes in the species
concentration, regardless the new positive equilibrium reached by the system.
Such a property has been proven to be fundamentally important in certain gene
regulatory networks and signaling systems. In the present paper, we
mathematically prove that a well-known class of ACR systems studied by Shinar
and Feinberg in 2010 hides an internal integral structure. This structure
confers these systems with a higher degree of robustness that what was
previously unknown. In particular, disturbances much more general than sudden
changes in the species concentrations can be rejected, and robust perfect
adaptation is achieved. Significantly, we show that these properties are
maintained when the system is interconnected with other chemical reaction
networks. This key feature enables design of insulator devices that are able to
buffer the loading effect from downstream systems - a crucial requirement for
modular circuit design in synthetic biology.
