Failure of channelling to maintain low concentrations of metabolic intermediates

Computer modelling has been used to investigate the effect of direct transfer of metabolites between consecutive enzymes (channelling) on the free concentrations of the channelled metabolites. When a channelled intermediate cannot participate in any other reactions, any increase in channelling tends to increase its free concentration, albeit very slightly, unless the increase in net flux brought about by the channel is compensated for by a simultaneous decrease in the activity of the route through the free intermediate, in which case channelling has no effect at all on the free steady-state concentration of the channelled intermediate. If the free intermediate is capable of participating in side reactions, channelling can decrease these side reactions, but only slightly unless virtually all of the final product results from flux through the channel and the rate constants for the direct pathway are virtually zero. In general, channelling appears not to provide a useful mechanism for maintaining intermediate concentrations at low levels. Numerous systems have been reported in which enzymes catalysing consecutive reactions in metabolic pathways are capable of forming loose complexes with one another in solu-tion: for example, in a recent review Keleti [l] summarizes different kinds of experiment that suggest that aldolase form