Phase dependent phase shifts induced by pyruvate and acetaldehyde in oscillating NADH of yeast cells

Betz, A.; Becker, Jörn‐Ullrich

doi:10.1080/09291017509359480

Cited by 20 publications

(21 citation statements)

References 6 publications

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“…These phase shifts depend on the phase of addition (17,43). For the heat production rate, the same relation was found as for NADH: a maximal phase shift at 0°, i.e.…”

Section: Oscillations In Heat Productionsupporting

confidence: 54%

Synchronized Heat Flux Oscillations in Yeast Cell Populations

Teusink

Larsson

Diderich

et al. 1996

Journal of Biological Chemistry

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Microcalorimetry was adapted to the study of glycolytic oscillations in suspensions of intact yeast cells. A correction procedure was developed for the distortion of the amplitude and phase of the heat signal, caused by the slow response of the calorimeter. This made it possible to observe oscillations in the heat production rate with a period of less than 1 min, and a relative amplitude of 5-10%. By simultaneously measuring the heat flux and concentrations of glycolytic metabolites, and by comparing acetaldehyde-induced phase shifts of the heat flux oscillations with those of NADH oscillations, the heat flux was found to be 100°out of phase with glucose 6-phosphate, 80°out of phase with fructose 1,6-bisphosphate, and in phase with NADH. The flux measurement made possible by microcalorimetry allowed the recognition of (i) changes in metabolic capacity that may affect glycolytic dynamics, (ii) implications of glucose carrier kinetics for glycolytic dynamics and (iii) the continued requirement for an acetaldehyde trapping agent for the oscillations.Under certain experimental conditions, suspensions of yeast cells exhibit sustained oscillations in the concentrations of several glycolytic intermediates (1-3). Glycolytic oscillations in yeast have been discovered some 30 years ago (see, for review, Ref. 4) and have subsequently been found in extracts of many organisms, including insects (5), mammals (6), and plants (7). Also with respect to yeast, the study of glycolytic oscillations has been mainly carried out in cell-free extracts. In suspensions of intact yeast cells, most reported oscillations were damped (see, e.g.,. Sustained oscillations have also been observed (1, 11). More recently, the experimental conditions have been explicitly described that determine whether sustained or transient oscillations are obtained in suspensions of intact yeast cells (3,12). Sustained oscillations continue until the cells run out of substrate (Ref. 12; see also Fig. 4); damped oscillations disappear before the substrate is consumed. We use these sustained oscillations in suspensions of yeast cells as a model system to study the control of timedependent, yet steady, metabolic systems.The fact that sustained oscillations can be observed in a population of cells, implies that some synchronization mechanism prevents the cells from running out of phase (13-16).Recently, acetaldehyde was identified as the metabolite that couples the individual cells (17). Consequently, not only control by internal parameters is of interest, but also the control via the extracellular acetaldehyde concentration. The latter control cannot be studied in cell-free extracts.The metabolic oscillations are readily monitored through NAD(P)H fluorescence. To monitor other metabolites, samples have to be taken, quenched and extracted, either with trichloroacetic or perchloric acid (8), or with methanol and chloroform at Ϫ40°C (18). Crucial thermodynamic variables such as the redox potential and the phosphorylation potential oscillate significantly (3,19). From...

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“…These phase shifts depend on the phase of addition (17,43). For the heat production rate, the same relation was found as for NADH: a maximal phase shift at 0°, i.e.…”

Section: Oscillations In Heat Productionsupporting

confidence: 54%

Synchronized Heat Flux Oscillations in Yeast Cell Populations

Teusink

Larsson

Diderich

et al. 1996

Journal of Biological Chemistry

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“…The authors also found that the oscillations were even more damped in the absence of aldehyde traps, such as KCN or extracellularly added NADH and alcohol dehydrogenase, which let to the speculation that acetaldehyde secreted by the cells is a desynchroniser. On the contrary, Betz and Becker [54] showed that phase shifts could be induced by adding acetaldehyde or pyruvate, which suggested that these compounds might be involved in the signalling. Richard et al [50] showed that for sustained oscillations an environment which removes the acetaldehyde at a certain rate is essential.…”

Section: Synchronisation Of Glycolytic Oscillations In Intact Yeast Cmentioning

confidence: 98%

The rhythm of yeast

2003

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Although yeast are unicellular and comparatively simple organisms, they have a sense of time which is not related to reproduction cycles. The glycolytic pathway exhibits oscillatory behaviour, i.e. the metabolite concentrations oscillate around phosphofructokinase. The frequency of these oscillations is about 1 min when using intact cells. Also a yeast cell extract can oscillate, though with a lower frequency. With intact cells the macroscopic oscillations can only be observed when most of the cells oscillate in concert. Transient oscillations can be observed upon simultaneous induction; sustained oscillations require an active synchronisation mechanism. Such an active synchronisation mechanism, which involves acetaldehyde as a signalling compound, operates under certain conditions. How common these oscillations are in the absence of a synchronisation mechanism is an open question. Under aerobic conditions an oscillatory metabolism can also be observed, but with a much lower frequency than the glycolytic oscillations. The frequency is between one and several hours. These oscillations are partly related to the reproductive cycle, i.e. the budding index also oscillates; however, under some conditions they are unrelated to the reproductive cycle, i.e. the budding index is constant. These oscillations also have an active synchronisation mechanism, which involves hydrogen sulfide as a synchronising agent. Oscillations with a frequency of days can be observed with yeast colonies on plates. Here the oscillations have a synchronisation mechanism which uses ammonia as a synchronising agent.

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“…An appropriate way to investigate the effect of a substance on an oscillating system is by perturbation experiments. Experimentally, this was investigated for pulses of acetaldehyde given to the external medium of a yeast suspension [13,14]. This choice was encouraged by the idea that a metabolite which couples the individual cells should be able to affect the intracellular oscillatory dynamics.…”

Section: Phase Response After Addition Of Acetaldehydementioning

confidence: 99%

“…A number of experiments, studying the nature of coupling, have suggested that cells interact by the exchange of a metabolic intermediate via the external medium. Ethanol, pyruvate and acetaldehyde have been discussed as candidates for the coupling metabolites [10,11,14]. Recent studies have yielded strong evidence that acetaldehyde mediates the coupling [13].…”

Section: Introductionmentioning

confidence: 99%

Effect of cellular interaction on glycolytic oscillations in yeast: a theoretical investigation

Wolf¹

2000

Biochem. J.

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On the basis of a detailed model of yeast glycolysis, the effect of intercellular dynamics is analysed theoretically. The model includes the main steps of anaerobic glycolysis, and the production of ethanol and glycerol. Transmembrane diffusion of acetaldehyde is included, since it has been hypothesized that this substance mediates the interaction. Depending on the kinetic parameter, the single-cell model shows both stationary and oscillatory behaviour. This agrees with experimental data with respect to metabolite concentrations and phase shifts. The inclusion of intercellular coupling leads to a variety of dynamical modes, such as synchronous oscillations, and different kinds of asynchronous behavior. These oscillations can co-exist, leading to bi- and tri-rhythmicity. The corresponding parameter regions have been identified by a bifurcation analysis. The oscillatory dynamics of synchronized cell populations are investigated by calculating the phase responses to acetaldehyde pulses. Simulations are performed with respect to the synchronization of two subpopulations that are oscillating out of phase before mixing. The effect of the various process on synchronization is characterized quantitatively. While continuous exchange of acetaldehyde might synchronize the oscillations for appropriate sets of parameter values, the calculated synchronization time is longer than that observed experimentally. It is concluded either that addition to the transmembrane exchange of acetaldehyde, other processes may contribute to intercellular coupling, or that intracellular regulator feedback plays a role in the acceleration of the synchronization. for appropriate sets of parameter values, the calculated synchronization time is longer than that observed experimentally. It is concluded either that addition to the transmembrane exchange of acetaldehyde, other processes may contribute to intercellular coupling, or that intracellular regulator feedback plays a role in the acceleration of the synchronization.

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Phase dependent phase shifts induced by pyruvate and acetaldehyde in oscillating NADH of yeast cells

Cited by 20 publications

References 6 publications

Synchronized Heat Flux Oscillations in Yeast Cell Populations

Synchronized Heat Flux Oscillations in Yeast Cell Populations

The rhythm of yeast

Effect of cellular interaction on glycolytic oscillations in yeast: a theoretical investigation

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