Identifying the conditions necessary for the thioredoxin ultrasensitive response

SummaryThioredoxin, glutaredoxin, and peroxiredoxin systems (collectively called redoxins) play critical roles in a large number of redox-sensitive cellular processes. These systems are linked to each other by coupled redox cycles and by common reaction intermediates into a larger network.Previous results from a realistic computational model of the Escherichia coli thioredoxin system developed in our group have revealed several modes of kinetic regulation in the system. Amongst others, the coupling of the thioredoxin and peroxiredoxin redox cycles was shown to exhibit the potential for ultrasensitive changes in the thioredoxin concentration and the flux through other thioredoxin-dependent processes in response to changes in the thioredoxin reductase level. Here, we analyse the basis for this ultrasensitive response using kinetic modelling and metabolic control analysis and derive quantitative conditions that must be fulfilled for ultrasensitivity to occur.