Why the Phosphotransferase System of Escherichia Coli Escapes the Diffusion Limitation of Signal Transduction, Transport and Metabolism that Confronts Mammalian Cells

摘要

Wherever components of a metabolic pathway act at different locations in the cell, diffusion will cause concentration gradients. Rough estimates suggest that such gradients can be substantial if not prohibitive. We calculated the implications of diffusion for the phosphoenopyruvate-dependent phosphotrasferase system (PTS) of Escherichia coli in silicon cells of various magnitudes. For a cell of bactrial size we found no significant diffusion limitation of flux. No significant concentration gradients of phosphorylated and non-phosphorylated enzyme species were found except for non-phosphorylated IIA(sup GLC). Due to its relatively low concentration the concentration gradient for this sepcies was substantial. This should have consequences because the phosphorylation state of IIA(sup GLC) is an important intracellular signal. For mammalian cell sizes, significant diffusion limitation, as well as strong concentration gradients in many Pts components, and strong effects on glucose and energy signaling were calculated. We calculated that the PTS may sense both extracellular glucose and the intracellular free-energy statae. We discuss (1) that in the small bacterial cell the PTS needs 4 enzymes to maintain inward flux and both glucose and free-energy sensing ability. (2) that the effects of diffusion on cell function should prevent this highly effective bacterial system from functioning in eukaryotic cells, (3) that in the larger eukaryotic cell any chain of mobile proteins can neither sustain the same volumetric flux as in bacteria nor transmit a signal far into the cell, and (4) that systems such as these may exhibt spatial differentiation in ther sensitivity to different signals.