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Phosphofructokinase controls the acetaldehyde-induced phase shift in isolated yeast glycolytic oscillators

Abstract (Expand)

Abstract The response of oscillatory systems to external perturbations is crucial for emergent properties such as synchronisation and phase locking and can be quantified in a phase response curve (PRC). …hase response curve (PRC). In individual, oscillating yeast cells, we characterised experimentally the phase response of glycolytic oscillations for external acetaldehyde pulses and followed the transduction of the perturbation through the system. Subsequently, we analysed the control of the relevant system components in a detailed mechanistic model. The observed responses are interpreted in terms of the functional coupling and regulation in the reaction network. We find that our model quantitatively predicts the phase-dependent phase shift observed in the experimental data. The phase shift is in agreement with an adaptation leading to synchronisation with an external signal. Our model analysis establishes that phosphofructokinase plays a key role in the phase shift dynamics as shown in the PRC and adaptation time to external perturbations. Specific mechanism-based interventions, made possible through such analyses of detailed models, can improve upon standard trial and error methods, e.g. melatonin supplementation to overcome jet-lag, which are error-prone, specifically, since the effects are phase dependent and dose dependent. The models by Gustavsson and Goldbeter discussed in the text can be obtained from the JWS Online simulation database: (https://jjj.bio.vu.nl/models/gustavsson5 and https://jjj.bio.vu.nl/models/goldbeter1)

Authors: David D. van Niekerk, Anna-Karin Gustavsson, Martin Mojica-Benavides, Caroline B. Adiels, Mattias Goksör, Jacky L. Snoep

Date Published: 31st Jan 2019

Publication Type: Journal

Phosphoglycerate kinase acts as a futile cycle at high temperature.

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In (hyper)thermophilic organisms metabolic processes have to be adapted to function optimally at high temperature. We compared the gluconeogenic conversion of 3-phosphoglycerate via 1,3-bisphosphoglycerate … to glyceraldehyde-3-phosphate at 30 degrees C and at 70 degrees C. At 30 degrees C it was possible to produce 1,3-bisphosphoglycerate from 3-phosphoglycerate with phosphoglycerate kinase, but at 70 degrees C, 1,3-bisphosphoglycerate was dephosphorylated rapidly to 3-phosphoglycerate, effectively turning the phosphoglycerate kinase into a futile cycle. When phosphoglycerate kinase was incubated together with glyceraldehyde 3-phosphate dehydrogenase it was possible to convert 3-phosphoglycerate to glyceraldehyde 3-phosphate, both at 30 degrees C and at 70 degrees C, however, at 70 degrees C only low concentrations of product were observed due to thermal instability of glyceraldehyde 3-phosphate. Thus, thermolabile intermediates challenge central metabolic reactions and require special adaptation strategies for life at high temperature.

Authors: T. Kouril, J. J. Eicher, B. Siebers, J. L. Snoep

Date Published: 7th Oct 2017

Publication Type: Not specified

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