In Vivo Analysis of Glucose-Induced Fast Changes in Yeast Adenine Nucleotide Pool Applying a Rapid Sampling Technique

Theobald, Uwe; Mailinger, Werner; Reuß, Matthias; Rizzi, Manfred

doi:10.1006/abio.1993.1452

Cited by 185 publications

(183 citation statements)

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“…When calorie-restricted yeast is supplemented with fresh nutrients, growth accelerates quickly; as a result, ATP turnover increases rapidly [45]. However, a decrease in ATP cannot be tolerated, because an activated cellular stress program would hinder further growth [25,26].…”

Section: Module-specific Reporter Metabolites Adjust Transcription Comentioning

confidence: 99%

Regulatory crosstalk of the metabolic network

Grüning

Lehrach

Ralser

2010

Trends in Biochemical Sciences

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The metabolic network has a modular architecture, is robust to perturbations, and responds to biological stimuli and environmental conditions. Through monitoring by metabolite responsive macromolecules, metabolic pathways interact with the transcriptome and proteome. Whereas pathway interconnecting cofactors and substrates report on the overall state of the network, specialised intermediates measure the activity of individual functional units. Transitions in the network affect many of these regulatory metabolites, facilitating the parallel regulation of the timing and control of diverse biological processes. The metabolic network controls its own balance, chromatin structure and the biosynthesis of molecular cofactors; moreover, metabolic shifts are crucial in the response to oxidative stress and play a regulatory role in cancer.Evolution of the metabolic network and its structure Life probably began with the formation of compartmentalised autocatalytic chemical cycles. With the appearance of complex catalysts (ribonucleic acid-or protein-based enzymes), these cycles gained complexity, and evolved in their effectiveness and robustness [1]. These metabolic pathways now form the basis for life.As was the case for the first primitive life forms, the survival of today's complex organisms depends on the robustness and functionality of the metabolic framework [2]. To prevent and counteract perturbations in the flux, many biological control and sensor systems have evolved around the metabolic network. Metabolic pathways provide the cell with energy and supply macromolecular synthesis pathways with their required intermediates. They also balance metabolic systems under a variety of physiological conditions, and act as transducers and sensor systems for environmental conditions and stimuli. In addition, metabolic pathways are essential for crosstalk between metabolic regulatory components and the cellular transcriptome and proteome.As early as the 1960s, the principle that cells alter their gene expression in response to metabolic requirements has been known. The seminal work of Jacob and Monod, investigating the lac operon, uncovered one of the first examples of chemical-genetic regulation, by which bacterial cells adjust their enzyme production to the nutrient supply [3]. However, only recently have the broader implications of this principle emerged. Indeed, changes in the metabolic network not only control the metabolome, but they also have wide-ranging regulatory functions throughout biology.Most of the biochemical mechanisms that link the metabolic network to the transcriptome and proteome are incompletely understood. However, one type of regulation appears to be common: representative network intermediates bind to and modulate sensor function and activity of transcription factors, translational regulators, chromatin, enzymes, RNA molecules, and ion channels. Significant transcriptional changes around these intermediates identified them as reporter metabolites [4,5]. The use of intermediates as activity reporters ne...

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Section: Module-specific Reporter Metabolites Adjust Transcription Comentioning

confidence: 99%

Regulatory crosstalk of the metabolic network

Grüning

Lehrach

Ralser

2010

Trends in Biochemical Sciences

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“…Theobald et al, 1993 developed a fast manual sampling technique with which samples could be withdrawn in a fraction of a second with intervals of 2 -5 seconds between samples. A comparable system has been developed by Lange et al, (2001).…”

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Development and application of a differential method for reliable metabolome analysis in Escherichia coli

Taymaz-Nikerel

Mey

Ras

et al. 2009

Analytical Biochemistry

145

129

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“…Thus, glucose is a metabolic substrate acting as an extracellular source of free energy powering life. In yeast, a strong negative correlation between glycolytic flux and intracellular ATP concentration has been widely documented (1)(2)(3). Because glucose catabolism is the main source of ATP-derived free energy, this observation (the higher the rate of glycolysis the lower the ATP content) is a counterintuitive phenomenon, which has been referred to as the ATP paradox.…”

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“…Thus, this regime is referred to as dissipative maximum output power (DMOP). 1 The other regime represents an excellent compromise between high output power and low dissipation, so it is named efficient maximum output power (EMOP). More interestingly, it will be shown that the ATP paradox can be the expression of a molecular mechanism linking, throughout the intracellular level of ATP, the signal (low or high fuel levels) with the appropriate thermodynamic regime (EMOP or DMOP, respectively).…”

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confidence: 99%

The ATP Paradox Is the Expression of an Economizing Fuel Mechanism

Aledo

Valle

2004

Journal of Biological Chemistry

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The strong negative correlation between glycolytic flux and intracellular ATP concentration observed in yeast has long been an intriguing and counterintuitive phenomenon, which has been referred to as the ATP paradox. Herein, using principles of irreversible thermodynamics it was shown that if the ATP-consuming pathways are more sensitive to extracellular glucose than glycolysis, then upon glucose addition glycolysis performance can switch from an efficient working regime to a dissipative regime, and vice versa, depending on glucose availability. The efficient regime represents a good compromise between high output power and low dissipation, whereas the dissipative working regime offers a higher output power although at a high glucose cost. The physiological and evolutionary implications of this switch strategy are discussed.Glycolysis is a metabolic pathway providing cells with energy in the form of ATP, which can be used to drive cellular processes. Thus, glucose is a metabolic substrate acting as an extracellular source of free energy powering life. In yeast, a strong negative correlation between glycolytic flux and intracellular ATP concentration has been widely documented (1-3). Because glucose catabolism is the main source of ATP-derived free energy, this observation (the higher the rate of glycolysis the lower the ATP content) is a counterintuitive phenomenon, which has been referred to as the ATP paradox. A sudden transition from glucose limitation to glucose excess leads to a new steady state at increased glycolytic flux with a sustained decrease in the ATP levels (3). Because ADP phosphorylation is tightly coupled to glucose breakdown, a higher glycolytic flux implies that more ATP is being formed. The subsequent increase in the flux throughout ATP-consuming reactions was thought to be brought about by an increased ATP/ADP ratio. Therefore, the decreased steady state level of ATP constitutes an intriguing observation. Somsen et al.(3), in an elegant work employing metabolic control analysis and a simple model, concluded that the experimental ATP changes can only be explained if the sensitivities of ATP-consuming routes to extracellular glucose are higher than that of the glycolytic pathway. Although this particular sensitivity of anabolic pathways solves the problem of how a drop in ATP concentration triggered by high glucose levels is possible, one question still remains open. What are the physiological implications of this behavior we have termed as the ATP paradox? In other words, what is the purpose of the stronger sensitivity to the level of extracellular fuel exhibited by ATP-utilizing pathways with respect to that of ATP-producing pathways?

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In Vivo Analysis of Glucose-Induced Fast Changes in Yeast Adenine Nucleotide Pool Applying a Rapid Sampling Technique

Cited by 185 publications

References 0 publications

Regulatory crosstalk of the metabolic network

Regulatory crosstalk of the metabolic network

Development and application of a differential method for reliable metabolome analysis in Escherichia coli

The ATP Paradox Is the Expression of an Economizing Fuel Mechanism

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