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The transport of PTS-sugars other than glucose can affect the phosphorylation of Enzyme IIAGlc simply by generating competition for phosphorylation between the phosphotransfer proteins. Such competition indirectly regulates adenylate cyclase activity.
This type of regulation has been proposed by Crasnier-Mednansky et al. in 1997 [Microbiology]. It occurs when enhanced transport of the PTS-sugar fructose takes place.
The sequential transfer of phosphate from PEP to fructose does not involve, unlike other PTS, HPr but the diphosphoryl transfer protein, FruB [Medline] which was renamed Enzyme IIAMHFru.
In fruR mutant strains lacking the fructose repressor FruR (also called Cra), Enzyme IIAGlc is largely unphosphorylated when cells are grown in fructose-containing medium. In such conditions the fructose operon (fruBKA) is over-expressed thus leading to competition for phosphorylation between Enzyme IIAMHFru (FruB) and HPr.
Because of the competition between the phosphoproteins, phosphorylation of Enzyme IIAGlc is impaired; as a consequence adenylate cyclase becomes 'inactive' (in idle mode). Therefore fruR mutant strains grown on fructose exhibit cAMP levels that are much lower than those in wild-type strains grown on fructose. With carbon sources other than fructose, cAMP levels of fruR and wild-type strains are comparable [Microbiology]1. One of the physiological consequences of Enzyme IIAGlc unphosphorylation is that fructose can substitute for glucose in producing diauxie but only in fruR strains2 [MIeJ].
Competition for phosphorylation between PTS constituents seems to be a crucial determinant of adenylate cyclase regulation, as exemplified by the study of fruR mutant strains.
Competition for phosphorylation is also likely to occur when transport of several PTS-sugars takes place. Limited phosphoryl flux may be a constituent of the winner-take-all behavior, as revealed by theoretical studies of metabolic switching in the PTS [Biophys J].
In the case of a non-PTS carbon source, for example glucose-6-phosphate, the regulation of adenylate cyclase activity is more difficult to apprehend, as glucose-6-phosphate transport or metabolism is not known to involve PTS proteins, especially Enzyme IIAGlc.
1 In the 2007 J Bacteriol article "Correlation between growth rates, EIIA phosphorylation, and intracellular cAMP levels in Escherichia coli K-12" Bettenbrock et al. improperly reported, by referring to the 1997 Microbiology article, that lack of HPr enhances cAMP production in fructose-grown E. coli. Generally lack of HPr results in a low production of cAMP!
2E. coli wild-type strains exhibit diauxic growth with glucose or mannitol as the "preferred" carbon source but not with fructose [Jacques Monod, Ph.D. thesis, 1942] [Microbiol Mol Biol Rev].
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