Fig. 5

Schemes of hypothesized channeling and its influence on catabolite repression. An enzymatic pathway of sequential metabolites W, X, Y, and Z forms a channel. Delta represents the presence of a bottleneck that limits flux through the channel. a In a fully channeled network, most substrates exist within the channel with few substrates existing in cytosol. The pulse of ¹³C (asterisk) into the channeled pathway results in sequential and fast labeling of metabolites W, X, Y, and Z. b In a fractured channel, a disturbance in an enzyme (X→Y) causes accumulation of X in the cytosol, which is metabolically less active. After the pulse of ¹³C (asterisk), the labeling of bulk X* will be diluted by unlabeled X^o in the cytosol during LC–MS analysis. The downstream metabolites Y and Z may show faster ¹³C-labeling if their unlabeled pools in cytosol are small. In this case, the pulse of ¹³C and measurement of metabolite labeling dynamics can capture the features of channeling. c Substrate channeling can be another factor leading to CCR. The presence of channeling favors fast W conversion through the channeled pathway, while diffusion of cytosol metabolite (X) from secondary substrate (U) into channeled pathway becomes limited. d Catabolite repression is reduced if the channeled pathway flux is downregulated, allowing for cytosol X to diffuse into the channeled pathway