Channelling can affect concentrations of metabolic intermediates at constant net flux: artefact or reality?

We show that if a metabolic intermediate is directly transferred ('channelled') from an enzyme that catalyses its production to another that uses it as substrate, there is no change in its free concentration compared with a system with the same net flux in which there is no direct transfer. Thus the widespread idea that channelling provides a mechanism for decreasing metabolite concentrations at constant flux is false. Results from computer simulation that suggest otherwise [Mendes, P., Kell, D. B. & Westerhoff, H. V. (1992) Eur. J. Biochem. 204, 257-266] are artefacts either of variations in flux or of alterations in opposite directions of the activities of the relevant enzymes.