Transcriptome meets metabolome: hierarchical and metabolic regulation of the glycolytic pathway.
The fact that information flows from DNA to RNA to protein to function suggests that regulation is 'hierarchical', i.e. dominated by regulation of gene expression. In the case of dominant regulation at the metabolic level, however, there is no quantitative relationship between mRNA levels and function. We here develop a method to quantitate the relative contributions of metabolic and hierarchical regulation. Applying this method to the glycolytic flux in three species of parasitic protists, we conclude that it is rarely regulated by gene expression alone. This casts strong doubts on whether transcriptome and proteome analysis suffices to assess biological function.
ter Kuile
B H
BH
Leiden Institute of Chemistry, The Netherlands. b.terkuile@chem.leidenuniv.nl
Westerhoff
H V
HV
D000818:Animals; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D007893:Leishmania donovani / Q000254:growth & development / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008954:Models, Biological; D010732:Phosphofructokinase-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D014246:Trichomonas vaginalis / Q000254:growth & development / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000254:growth & development / Q000378:metabolism*
D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase; D010732:Phosphofructokinase-1; D005956:Glucose-6-Phosphate Isomerase; D005947:Glucose