On 2014 May 14, Martine Crasnier-Mednansky commented:

The feedback strategy established by Doucette CD, 2011 relates to data obtained under conditions of 'extreme' catabolite repression elicited by nitrogen limitation. A direct inhibitory effect of α-ketoglutarate on Enzyme I inhibits phosphorylation of the components of the phosphotransferase system (PTS), including phosphorylation of EnzymeIIAGlc which activates adenylate cyclase. Therefore, cAMP-mediated catabolite repression occurs in these conditions. Another not-yet propounded effect of an increase in α-ketoglutarate is an enhanced inducer exclusion, which further hinders uptake of carbon sources other than PTS substrates. Under nitrogen-limited conditions, β-galactosidase synthesis in a wild-type strain growing on glucose is most likely affected by inducer exclusion. Thus, nitrogen-limited growth may not 'rely completely' on cAMP-mediated gene regulation as transcriptional regulation by cAMP and inducer exclusion both interfere with β-galactosidase synthesis Crasnier-Mednansky M, 2008. By not taking into account inducer exclusion the authors undermine the power of 'quantitative physiology'. Within the same frame of thought, using pts strains grown on lactose to measure β-galactosidase activity is physiologically irrelevant.

In sharp contrast with the present data, Daniel J, 1986 reported that α-ketoglutarate (or pyruvate indirectly by accumulation of α-ketoglutarate) caused repression of the lac operon - but not oxaloacetate. In addition repression did not occur in crr strains (lacking Enzyme IIAGlc) in support of Doucette CD, 2011.

On 2014 May 14, Martine Crasnier-Mednansky commented:

The feedback strategy established by Doucette CD, 2011 relates to data obtained under conditions of 'extreme' catabolite repression elicited by nitrogen limitation. A direct inhibitory effect of α-ketoglutarate on Enzyme I inhibits phosphorylation of the components of the phosphotransferase system (PTS), including phosphorylation of EnzymeIIAGlc which activates adenylate cyclase. Therefore, cAMP-mediated catabolite repression occurs in these conditions. Another not-yet propounded effect of an increase in α-ketoglutarate is an enhanced inducer exclusion, which further hinders uptake of carbon sources other than PTS substrates. Under nitrogen-limited conditions, β-galactosidase synthesis in a wild-type strain growing on glucose is most likely affected by inducer exclusion. Thus, nitrogen-limited growth may not 'rely completely' on cAMP-mediated gene regulation as transcriptional regulation by cAMP and inducer exclusion both interfere with β-galactosidase synthesis Crasnier-Mednansky M, 2008. By not taking into account inducer exclusion the authors undermine the power of 'quantitative physiology'. Within the same frame of thought, using pts strains grown on lactose to measure β-galactosidase activity is physiologically irrelevant.

In sharp contrast with the present data, Daniel J, 1986 reported that α-ketoglutarate (or pyruvate indirectly by accumulation of α-ketoglutarate) caused repression of the lac operon - but not oxaloacetate. In addition repression did not occur in crr strains (lacking Enzyme IIAGlc) in support of Doucette CD, 2011.