Escherichia coli adenylate cyclase homepage

Glucose 6-phosphate is transported into the cell via the Uhp system (Uptake hexose phosphate) which is inducible by extracellular glucose 6-phophate.  The Uhp system consists of a permease UhpT (encoded by uhpT) whose transcription is regulated by the UhpABC system.  UhpA and UhpB belong to the family of "two-component regulatory systems" [Nature Structural Biology].  In the presence of external glucose 6-phosphate, membrane-bound UhpC interacts with membrane-bound UhpB, the sensor kinase.  Phosphorylation of UhpA (the response regulator) by UhpB promotes transcription of the uhpT gene.  Interestingly, it was shown that the kinase domain of inactive UhpB can bind and sequester UhpA [JB].  Finally, efficient transcription of uhpT requires both UhpA and the CAP-cAMP complex [JMB].

UhpT has a broad range of substrates.  Cyclic AMP levels in strains growing in minimal medium supplemented with any one of the UhpT substrates are low (in fact among the lowest as compared to other carbon sources including glucose) provided that the Uhp system is fully induced.  Unfortunately, it is still not understood how glucose 6-phosphate transport and/or utilization affect adenylate cyclase activity.  Phosphorylated Enzyme IIA^glc, the major regulator of adenylate cyclase, is not a priori involved in glucose 6-phosphate transport and utilization.  However, one can question the phosphorylation state of Enzyme IIA^glc during glucose 6-phosphate transport and utilization.

In 1996, it was shown by V. Dumay and coworkers that glucose 6-phosphate does not cause inducer exclusion [Microbiology]¹.  It is therefore unlikely that glucose 6-phosphate transport and/or utilization indirectly regulate adenylate cyclase by a mechanism involving dephosphorylation of Enzyme IIA^glc.  Furthermore it was concluded by V. Dumay and coworkers that regulation of adenylate cyclase is not related to glucose 6-phosphate metabolism but occurs during glucose 6-phosphate transport by a still unknown mechanism.

In 1998, the finding that glucose 6-phosphate does not cause inducer exclusion was challenged by B. Hogema and coworkers [Molecular Microbiology].  It was proposed that Enzyme IIA^glc is dephosphorylated upon addition of glucose 6-phosphate in the culture medium.  The proposal however should be re-analyzed as E. coli Genetic Stock Center strain MG1655 (the only wild type strain used in the study) has been shown to present special features [JB]².  It was further proposed that glucose 6-phosphate metabolism is essential for controlling the phosphorylation state of Enzyme IIA^glc [Molecular Microbiology].

In 2002, T. Eppler and coworkers reported, in agreement with the findings of V. Dumay and coworkers, that metabolism of glucose 6-phosphate does not account for adenylate cyclase regulation [JB].  Also in agreement with V. Dumay and coworkers, they concluded that Enzyme IIA^glc is not dephosphorylated during glucose 6-phosphate transport.  They proposed that glucose 6-phosphate per se prevents the activation of adenylate cyclase by phosphorylated Enzyme IIA^glc.

Previously, in 1973, it was shown by H. Kornberg that transport, the primary function of the PTS, is inhibited by glucose 6-phosphate [Medline].  The molecular mechanism leading to this inhibition has yet to be established.  However one can question if it is the same mechanism that prevents activation of adenylate cyclase by phosphorylated Enzyme IIA^glc during glucose 6-phosphate transport.

Because PTS transport is inhibited by glucose 6-phosphate transport, glucose 6-phosphate is taken up preferentially when glucose (or any PTS-sugar) and glucose 6-phosphate are present in the culture medium.  This indicates that there is selectivity in transport leading to preferential uptake of substrates whose metabolism is most beneficial to Escherichia coli.

Footnotes:

¹ V. Dumay and coworkers stated that the mechanism of ‘catabolite repression’ by hexose phosphate [as referred to the mechanism of adenylate cyclase regulation] may be different from the one occurring with glucose unlike the misquoted statement found in the 2007 JB article "Analysis of the correlation between growth rates, EIIA^Crr phosphorylation and intracellular cAMP levels in Escherichia coli K-12" wherein K. Bettenbrock and coworkers improperly stated that V. Dumay and coworkers reported that glucose 6-phosphate did not elicit catabolite repression although cAMP levels were very low during growth with glucose 6-phosphate!

² Gene deletion in the same strain causes spontaneous secondary deletions in the flagellar regulon [JB].