Why the phosphotransferase system of Escherichia coli escapes the diffusion limitation of signal transduction, transport and metabolism that confronts mammalian cells

Wherever components of a metabolic pathway act at different locations in the cell, diffusion will cause concentration gradients. Rough estimates suggest thatsuch gradients can be substantial if not prohibitive. We calculated the implications of diffusion for thephosphoenolpyruvate-dependent phosphotransferasesystem (PTS) of <em>Escherichia coli</em> in silicon cells ofvarious magnitudes. For a cell of bacterial size we foundno significant diffusion limitation of flux. No significantconcentration gradients of phosphorylated and non-phosphorylatedenzyme species were found except fornon-phosphorylated IIA$^{Glc}$.Due to its relatively low concentration the concentration gradient for this species was substantial. This should have consequences becausethe phosphorylation state of IIA$^{Glc}$ is an importantintracellular signal. For mammalian cell sizes, significantdiffusion limitation, as well as strong concentrationgradients in many PTS components, and strong effects onglucose and energy signaling were calculated. We calculated that the PTS may sense both extracellular glucose and the intracellular free-energy state. We discuss(i) that in the small bacterial cell the PTS needs 4enzymes to maintain inward flux and both glucose andfree-energy sensing ability, (ii) that the effects ofdiffusion on cell function should prevent this highlyeffective bacterial system from functioning in eukaryoticcells, (iii) that in the larger eukaryotic cell any chain ofmobile proteins can neither sustain the same volumetricflux as in bacteria nor transmit a signal far into the cell,and (iv) that systems such as these may exhibit spatialdifferentiation in their sensitivity to different signals.