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. (C) 1998 Elsevier Science B.V. All rights reserved.