Figure 3.
Simulations of a multiply inhibited network yield distinct response shapes that depend on target connectivity. Substrates (black nodes) are metabolized through a series of Michaelis–Menten reactions (grey circles) from sources with constant reaction velocities to a limitless sink at the end-point. We calculated dose-matrix inhibitions of the end point velocity at RE to paired competitive inhibitors at various enzymes. The response surfaces for some combinations are shown, with the inhibitors indicated by joined markers. For Pathway A, same-target pairs produced Loewe additivity, and separated targets led to various Bliss boosts depending on where the targets were placed. Pathway B was added to investigate combination effects across pathways, with a bypass to ensure clear distinctions between cross-pathway boosting levels. Because both inputs are required for RAB, the junction is equivalent to a logical AND function. The negative feedback in Pathway B was introduced to represent processes like sterol biosynthesis in yeast. Inhibiting across pathways produced HSA-like masking effects, and inhibiting within the negative feedback loop yielded potentiation effects.