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

Thomas Nã¤Gele,Wolfram Weckwerth

doi:10.3389/fpls.2014.00365

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.

Highlights

Plant carbohydrates are the primary products of photosynthesis and are central to regulation of metabolism, development and growth
A KINETIC EQUATION FOR Snf1-related protein kinase 1 (SnRK1) ACTIVITY To estimate the impact of SnRK1 on the central carbohydrate metabolism and, vice versa, to analyze how its activity is affected by dynamic changes of metabolic inhibitor concentrations, a kinetic equation was derived to simulate the rate vSnRK1 by which sucrose phosphate synthase (SPS) is Frontiers in Plant Science | Plant Systems Biology phosphorylated and inactivated (Eq 1)
While it is known that low levels of glucose, high levels of sucrose and darkness induce the activity of SnRK1 (Rolland et al, 2006), a comprehensive characterization accounting for the differential impact of T6P, G1P, and G6P on SnRK1 activity (Nunes et al, 2013b) is difficult to obtain

Summary

Introduction

Plant carbohydrates are the primary products of photosynthesis and are central to regulation of metabolism, development and growth. Carbohydrates are synthesized as triose phosphates in chloroplasts. Under consumption of NADPH and ATP being generated by the photosynthetic electron transport chain, glycerate-3-phosphate is reduced to give triose phosphates, which can either be exported to the cytosol or be metabolized in the chloroplast as a substrate for starch synthesis (Heldt et al, 2011). Cytosolic triose phosphates are substrate for sucrose synthesis for which fructose-1,6-bisphosphatase (cFBPase) and sucrose phosphate synthase (SPS) have been identified as rate limiting (Stitt et al, 1983; Strand et al, 2000). The hexose phosphates are substrates for sucrose synthesis, glycolysis or the synthesis of organic and amino acids (Talts et al, 2004; Claeyssen and Rivoal, 2007; Ainsworth and Bush, 2011)

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