Control analysis of systems with reaction blocks that 'cross-talk'

Practical application of metabolic control analysis has been facilitated by use of the top-down approach, which divides a metabolic system into a small number of reaction blocks, linked by a few key intermediates. Previous papers have stressed that communication between blocks should be only through the explicit intermediates, 'cross-talk' between reaction blocks invalidated the approach. Here we show how the restriction is a result of the use of inhibitors of the blocks, and can be overcome if other system modulations are used. We also show a way to treat the related problem of enzymes that appear in more than one block such as the analysis of glycolytic substrate cycles into ATP consuming and net flux activities.