Response from Gonçalves and Planta

Abstract

We would like to present our point of view on the issues raised in the above article by Dr Boles concerning our recent review[1xGoncalves, P. and Planta, R.J. Trends Microbiol. 1998; 6: 314–319Abstract | Full Text | Full Text PDF | PubMed | Scopus (28)See all References[1].First, a clear distinction should be made between transcriptional activation of glycolytic genes and activation of glycolytic enzymatic activities. The work by the Zimmermann group has shown that the relationship between glycolytic metabolite concentrations and glycolytic enzymatic activities is complex and differs for virtually every enzyme tested[2xMuller, S. et al. J. Bacteriol. 1995; 177: 4517–4519PubMedSee all References[2]. This is not surprising because enzymatic activities can reflect the interplay between a variety of regulatory mechanisms. Therefore, they show the net result of this interplay, without showing which mechanisms make the most contribution to the final result.Second, transcriptional induction of glycolytic genes and repression of gluconeogenic genes is certainly one mechanism contributing to the activation of glycolysis by the presence of sugar in the medium. For the study of transcriptional regulation of glycolytic genes, we have chosen to focus on the PYK and PDC genes because of the considerable amount of data that is available for them. These two examples also emphasize the importance of having both enzyme activity (the Zimmermann group's results, which are cited in our paper) and northern blot results (from our lab). This point is discussed in Box 1 of our review[1xGoncalves, P. and Planta, R.J. Trends Microbiol. 1998; 6: 314–319Abstract | Full Text | Full Text PDF | PubMed | Scopus (28)See all References[1].Transcriptional analysis revealed a putative common trigger for the initial transcriptional response of both glycolytic and gluconeogenic genes; all the results correlate well with the ability to form glucose 6-phosphate (G6-P) or one of its nonglycolytic metabolites, while no further metabolism via glycolysis seems to be required[3xGoncalves, P.M. et al. Mol. Microbiol. 1997; 25: 483–493Crossref | PubMedSee all References, 4xYin, Z., Smith, R.J., and Brown, A.J. Mol. Microbiol. 1996; 20: 751–764Crossref | PubMed | Scopus (56)See all References].Third, the problem of the role of G6-P versus that of the hexokinases in signalling is particularly difficult to settle when glucose is the signalling sugar. The G6-P/hexokinase problem is relevant to various glucose-triggered signal transduction pathways (e.g. the cAMP pathway and the glucose repression pathway), which seem to require glucose phosphorylation for their activation[5xBeullens, M. et al. Eur. J. Biochem. 1988; 172: 227–231Crossref | PubMedSee all References, 6xRose, M., Albig, W., and Entian, K.D. Eur. J. Biochem. 1991; 199: 511–518Crossref | PubMedSee all References]. These pathways are not triggered by galactose or xylulose.However, if one assumes that galactose activates PYK and PDC transcription by essentially the same mechanism as glucose, then it is indeed unlikely that the hexokinases play a role in this particular signalling pathway[3xGoncalves, P.M. et al. Mol. Microbiol. 1997; 25: 483–493Crossref | PubMedSee all References[3].Unfortunately, with respect to the data concerning the regulation of the enzymatic activity of Eno2 and Adh1, described in Ref. [2xMuller, S. et al. J. Bacteriol. 1995; 177: 4517–4519PubMedSee all References[2], no comparative data on the level of transcription of the corresponding genes are available. Therefore, these data were not suitable to support or to disprove our model that formation of G6-P (and no further glycolytic metabolism) is required for the initial transcriptional induction of the glycolytic genes.