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Mathematical modeling reveals that metabolic feedback regulation of SnRK1 and hexokinase is sufficient to control sugar homeostasis from energy depletion to full recovery.

ABSTRACT: Sucrose and trehalose-6-phosphate (T6P) are central compounds in the regulation and orchestration of whole plant metabolism, growth, development, and flowering. To evaluate their highly complex and regulatory interaction with the two conserved sugar and energy sensors Snf1-related protein kinase 1 (SnRK1), an AMPK-related protein kinase, and hexokinase (Hxk), we developed a kinetic model which demonstrates the subtle metabolic control of sugar homeostasis in a wide range of concentrations without the need for changes in gene expression or protein concentrations. Our model approach is based on a comprehensive set of published metabolite concentrations under various conditions and coupled enzyme kinetics accounting for the role of SnRK1 and Hxk in the sugar and energy homeostasis. This allowed us to investigate interactions between sugar phosphates, such as T6P, which are metabolic inhibitors of SnRK1 and Hxk, and sucrose synthesis during the transition from carbon deficiency to availability. Model simulations and sensitivity analyses indicated that slight changes in SnRK1 activity induced by allosteric effectors may be sufficient to explain a dramatic readjustment of metabolic homeostasis. This may comprise up to 10-fold changes in metabolite concentrations. Further, the Hxk/T6P/SnRK1 interaction implemented in the model supports the interpretation of phenotypic and transcriptomic changes observed in Hxk overexpressing plants. Finally, our approach presents a theoretical framework to kinetically link metabolic networks to underlying regulatory instances.

SUBMITTER: Nagele T

PROVIDER: S-EPMC4112813 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Mathematical modeling reveals that metabolic feedback regulation of SnRK1 and hexokinase is sufficient to control sugar homeostasis from energy depletion to full recovery.

Nägele Thomas T Weckwerth Wolfram W

Frontiers in plant science 20140728

Sucrose and trehalose-6-phosphate (T6P) are central compounds in the regulation and orchestration of whole plant metabolism, growth, development, and flowering. To evaluate their highly complex and regulatory interaction with the two conserved sugar and energy sensors Snf1-related protein kinase 1 (SnRK1), an AMPK-related protein kinase, and hexokinase (Hxk), we developed a kinetic model which demonstrates the subtle metabolic control of sugar homeostasis in a wide range of concentrations withou ...[more]

PMID: 25120550

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Project description:Maintaining normal potassium (K+) concentrations in the extra- and intracellular fluid is critical for cell function. K+ homeostasis is achieved by ensuring proper distribution between extra- and intracellular fluid compartments and by matching K+ excretion with intake. The Na+-K+-ATPase pump facilitates K+ uptake into the skeletal muscle, where most K+ is stored. Na+-K+-ATPase activity is stimulated by insulin and aldosterone. The kidneys regulate long term K+ homeostasis by controlling the amount of K+ excreted through urine. Renal handling of K+ is mediated by a number of regulatory mechanisms, including an aldosterone-mediated feedback control, in which high extracellular K+ concentration stimulates aldosterone secretion, which enhances urine K+ excretion, and a gastrointestinal feedforward control mechanism, in which dietary K+ intake increases K+ excretion. Recently, a muscle-kidney cross talk signal has been hypothesized, where the K+ concentration in skeletal muscle cells directly affects urine K+ excretion without changes in extracellular K+ concentration. To understand how these mechanisms coordinate under different K+ challenges, we have developed a compartmental model of whole-body K+ regulation. The model represents the intra- and extracellular fluid compartments in a human (male) as well as a detailed kidney compartment. We included (i) the gastrointestinal feedforward control mechanism, (ii) the effect of insulin and (iii) aldosterone on Na+-K+-ATPase K+ uptake, and (iv) aldosterone stimulation of renal K+ secretion. We used this model to investigate the impact of regulatory mechanisms on K+ homeostasis. Model predictions showed how the regulatory mechanisms synthesize to ensure that the extra- and intracelluller fluid K+ concentrations remain in normal range in times of K+ loading and fasting. Additionally, we predict that without the hypothesized muscle-kidney cross talk signal, the model was unable to predict a return to normal extracellular K+ concentration after a period of high K+ loading or depletion.

Dataset Information

Mathematical modeling reveals that metabolic feedback regulation of SnRK1 and hexokinase is sufficient to control sugar homeostasis from energy depletion to full recovery.

Publications

Mathematical modeling reveals that metabolic feedback regulation of SnRK1 and hexokinase is sufficient to control sugar homeostasis from energy depletion to full recovery.

Similar Datasets

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