Temporal system-level organization of the switch from glycolytic to gluconeogenic operation in yeast

Autor: Stefan J. Jol, Nicola Zamboni, Jennifer C. Ewald, Paola Picotti, Anne Kümmel, Guillermo G Zampar, Ruedi Aebersold, Uwe Sauer, Matthias Heinemann, Bastian Niebel
Přispěvatelé: Molecular Systems Biology, University of Zurich, Heinemann, Matthias
Rok vydání: 2013
Předmět:
Time Factors
Proteome
Pentose Phosphate Pathway
SX00 SystemsX.ch
2604 Applied Mathematics
2400 General Immunology and Microbiology
Gene Expression Regulation
Fungal
Citrate synthase
Glycolysis
0303 health sciences
biology
Applied Mathematics
030302 biochemistry & molecular biology
Glyoxylates
Adaptation
Physiological
Fungal
Computational Theory and Mathematics
Biochemistry
Metabolome
General Agricultural and Biological Sciences
Information Systems
Phosphofructokinase
Saccharomyces cerevisiae Proteins
Physiological
Pyruvate Kinase
Glyoxylate cycle
Genetics and Molecular Biology
1100 General Agricultural and Biological Sciences
Citrate (si)-Synthase
Saccharomyces cerevisiae
Pentose phosphate pathway
General Biochemistry
Genetics and Molecular Biology
Article
Fluxome
03 medical and health sciences
1300 General Biochemistry
Genetics and Molecular Biology
Malate synthase
Metabolomics
Adaptation
030304 developmental biology
Diauxic shift
General Immunology and Microbiology
Gluconeogenesis
Malate Synthase
Glucose
Gene Expression Regulation
Phosphofructokinases
General Biochemistry
biology.protein
570 Life sciences
SX16 YeastX
Flux (metabolism)
Pyruvate kinase
NADP
Zdroj: Molecular Systems Biology, 9:651. Wiley-Blackwell
Molecular Systems Biology
MOLECULAR SYSTEMS BIOLOGY
Molecular Systems Biology, 9 (1)
Molecular systems biology
ISSN: 1744-4292
DOI: 10.5167/uzh-79184
Popis: Metabolome, proteome and physiology measurements were combined with mathematical modeling to unravel the temporal regulation of the metabolic fluxes during the diauxic shift in Saccharomyces cerevisiae.
The diauxic shift involves three main events: a reduction in the glycolytic flux and the production of storage compounds before glucose depletion; the reversion of carbon flow through glycolysis and onset of the glyoxylate cycle operation upon glucose exhaustion; and the shutting down of the pentose phosphate (PP) pathway with a change in the source of NADPH regeneration. The redistribution of fluxes toward the production of storage compounds prior glucose depletion drives glycolytic reactions closer to equilibrium, which is essential for the reversion of fluxes upon glucose exhaustion. The onset of the glyoxylate cycle is quantitatively more important than the activation of the tricarboxylic acid cycle for growth on ethanol. Flux through the PP pathway is halted in the later stages of the adaptation and NADPH regeneration is taken over by NADP-dependent enzymes in the glyoxylate cycle and ethanol metabolism.
The diauxic shift in Saccharomyces cerevisiae is an ideal model to study how eukaryotic cells readjust their metabolism from glycolytic to gluconeogenic operation. In this work, we generated time-resolved physiological data, quantitative metabolome (69 intracellular metabolites) and proteome (72 enzymes) profiles. We found that the diauxic shift is accomplished by three key events that are temporally organized: (i) a reduction in the glycolytic flux and the production of storage compounds before glucose depletion, mediated by downregulation of phosphofructokinase and pyruvate kinase reactions; (ii) upon glucose exhaustion, the reversion of carbon flow through glycolysis and onset of the glyoxylate cycle operation triggered by an increased expression of the enzymes that catalyze the malate synthase and cytosolic citrate synthase reactions; and (iii) in the later stages of the adaptation, the shutting down of the pentose phosphate pathway with a change in NADPH regeneration. Moreover, we identified the transcription factors associated with the observed changes in protein abundances. Taken together, our results represent an important contribution toward a systems-level understanding of how this adaptation is realized.
Databáze: OpenAIRE
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