The fluxes through glycolytic enzymes in Saccharomyces cerevisiae are predominantly regulated at posttranscriptional levels.
Metabolic fluxes may be regulated "hierarchically," e.g., by changes of gene expression that adjust enzyme capacities (V(max)) and/or "metabolically" by interactions of enzymes with substrates, products, or allosteric effectors. In the present study, a method is developed to dissect the hierarchical regulation into contributions by transcription, translation, protein degradation, and posttranslational modification. The method was applied to the regulation of fluxes through individual glycolytic enzymes when the yeast Saccharomyces cerevisiae was confronted with the absence of oxygen and the presence of benzoic acid depleting its ATP. Metabolic regulation largely contributed to the approximately 10-fold change in flux through the glycolytic enzymes. This contribution varied from 50 to 80%, depending on the glycolytic step and the cultivation condition tested. Within the 50-20% hierarchical regulation of fluxes, transcription played a minor role, whereas regulation of protein synthesis or degradation was the most important. These also contributed to 75-100% of the regulation of protein levels.
Daran-Lapujade
Pascale
P
Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC, Delft, The Netherlands. p.a.s.daran-lapujade@tudelft.nl
Rossell
Sergio
S
van Gulik
Walter M
WM
Luttik
Marijke A H
MA
de Groot
Marco J L
MJ
Slijper
Monique
M
Heck
Albert J R
AJ
Daran
Jean-Marc
JM
de Winde
Johannes H
JH
Westerhoff
Hans V
HV
Pronk
Jack T
JT
Bakker
Barbara M
BM
D000255:Adenosine Triphosphate / Q000378:metabolism; D019817:Benzoic Acid / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D006019:Glycolysis; D006706:Homeostasis; D007700:Kinetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D019817:Benzoic Acid