Comparison between elementary flux modes analysis and 13C-metabolic fluxes measured in bacterial and plant cells

<p>Abstract</p> <p>Background</p> <p>¹³C metabolic flux analysis is one of the pertinent ways to compare two or more physiological states. From a more theoretical standpoint, the structural properties of metabolic networks can be analysed to explore feasible metabolic behaviours and to define the boundaries of steady state flux distributions. Elementary flux mode analysis is one of the most efficient methods for performing this analysis. In this context, recent approaches have tended to compare experimental flux measurements with topological network analysis.</p> <p>Results</p> <p>Metabolic networks describing the main pathways of central carbon metabolism were set up for a bacteria species (<it>Corynebacterium glutamicum</it>) and a plant species (<it>Brassica napus</it>) for which experimental flux maps were available. The structural properties of each network were then studied using the concept of elementary flux modes. To do this, coefficients of flux efficiency were calculated for each reaction within the networks by using selected sets of elementary flux modes. Then the relative differences - reflecting the change of substrate <it>i.e</it>. a sugar source for <it>C</it>. <it>glutamicum </it>and a nitrogen source for <it>B</it>. <it>napus </it>- of both flux efficiency and flux measured experimentally were compared. For both organisms, there is a clear relationship between these parameters, thus indicating that the network structure described by the elementary flux modes had captured a significant part of the metabolic activity in both biological systems. In <it>B</it>. <it>napus</it>, the extension of the elementary flux mode analysis to an enlarged metabolic network still resulted in a clear relationship between the change in the coefficients and that of the measured fluxes. Nevertheless, the limitations of the method to fit some particular fluxes are discussed.</p> <p>Conclusion</p> <p>This consistency between EFM analysis and experimental flux measurements, validated on two metabolic systems allows us to conclude that elementary flux mode analysis could be a useful tool to complement ¹³C metabolic flux analysis, by allowing the prediction of changes in internal fluxes before carbon labelling experiments.</p

Incidental Detection of a Hodgkin Lymphoma on 18F-Choline PET/CT and Comparison With 18F-FDG in a Patient With Prostate Cancer

International audienceCombined PET/CT scanning with (18)F-FDG is in current use in Hodgkin lymphoma. New tracers have been developed, such as (18)F-choline in prostate cancer. Its use is under investigation in other solid tumors (eg, brain, liver, lung). We report a case of Hodgkin lymphoma incidentally detected on (18)F-choline PET/CT in a prostate cancer patient and show a comparison with (18)F-FDG PET/CT. (18)F-choline PET/CT detected more lymph node lesions than the (18)F-FDG PET/CT for this patient. Comparative studies of the 2 tracers might help fine-tune treatments and, in particular, delineate target zones in radiation therapy

Systematic study of a metabolic network

International audienc

Systematic study of a metabolic network

International audienc

Nitrogen-mediated metabolic patterns of susceptibility to Botrytis cinerea infection in tomato (Solanum lycopersicum) stems

International audienceSevere N stress allows an accumulation of C-based compounds but impedes that of N-based compounds required to lower the susceptibility of tomato stem to Botrytis cinerea . Abstract Botrytis cinerea , a necrotrophic filamentous fungus, forms potentially lethal lesions on the stems of infected plants. Contrasted levels of susceptibility to B. cinerea were obtained in a tomato cultivar grown on a range of nitrate concentration: low N supply resulted in high susceptibility while high N supply conferred a strong resistance. Metabolic deviations and physiological traits resulting from both infection and nitrogen limitation were investigated in the symptomless stem tissue surrounding the necrotic lesion. Prior to infection, nitrogen-deficient plants showed reduced levels of nitrogen-based compounds such as amino acids, proteins, and glutathione and elevated levels of carbon-based and defence compounds such as α-tomatine and chlorogenic acid. After B. cinerea inoculation, all plants displayed a few common responses, mainly alanine accumulation and galactinol depletion. The metabolome of resistant plants grown under high N supply showed no significant change after inoculation. On the contrary, the metabolome of susceptible plants grown under low N supply showed massive metabolic adjustments, including changes in central metabolism around glutamate and respiratory pathways, suggesting active resource mobilization and production of energy and reducing power. Redox and defence metabolisms were also stimulated by the infection in plants grown under low N supply; glutathione and chlorogenic acid accumulated, as well as metabolites with more controversial defensive roles, such as polyamines, GABA, branched-chain amino acids and phytosterols. Taken together, the results showed that nitrogen deficiency, although leading to an increase in secondary metabolites even before the pathogen attack, must have compromised the constitutive levels of defence proteins and delayed or attenuated the induced responses. The involvement of galactinol, alanine, cycloartenol and citramalate in the tomato stem response to B. cinerea is reported here for the first time

Nitrogen-mediated metabolic patterns of susceptibility to Botrytis cinerea infection in tomato (Solanum lycopersicum) stems

International audienceSevere N stress allows an accumulation of C-based compounds but impedes that of N-based compounds required to lower the susceptibility of tomato stem to Botrytis cinerea . Abstract Botrytis cinerea , a necrotrophic filamentous fungus, forms potentially lethal lesions on the stems of infected plants. Contrasted levels of susceptibility to B. cinerea were obtained in a tomato cultivar grown on a range of nitrate concentration: low N supply resulted in high susceptibility while high N supply conferred a strong resistance. Metabolic deviations and physiological traits resulting from both infection and nitrogen limitation were investigated in the symptomless stem tissue surrounding the necrotic lesion. Prior to infection, nitrogen-deficient plants showed reduced levels of nitrogen-based compounds such as amino acids, proteins, and glutathione and elevated levels of carbon-based and defence compounds such as α-tomatine and chlorogenic acid. After B. cinerea inoculation, all plants displayed a few common responses, mainly alanine accumulation and galactinol depletion. The metabolome of resistant plants grown under high N supply showed no significant change after inoculation. On the contrary, the metabolome of susceptible plants grown under low N supply showed massive metabolic adjustments, including changes in central metabolism around glutamate and respiratory pathways, suggesting active resource mobilization and production of energy and reducing power. Redox and defence metabolisms were also stimulated by the infection in plants grown under low N supply; glutathione and chlorogenic acid accumulated, as well as metabolites with more controversial defensive roles, such as polyamines, GABA, branched-chain amino acids and phytosterols. Taken together, the results showed that nitrogen deficiency, although leading to an increase in secondary metabolites even before the pathogen attack, must have compromised the constitutive levels of defence proteins and delayed or attenuated the induced responses. The involvement of galactinol, alanine, cycloartenol and citramalate in the tomato stem response to B. cinerea is reported here for the first time

How to optimize metabolites concentrations and fluxes in a metabolic pathway? Backgrounds and Basics

The modelling of metabolic pathways is developed here for application to sugar metabolism of tomatoes during fruit expansion. In the now classic calculation of network fluxes, we add concentrations. Under assumptions of steady state and of "minimal effort" as proposed in [1], fluxes and concentrations, respecting constraints of experimental measurements and of thermodynamics, are searched. In order to obtain a well-posed problem, a preliminary mathematical study is in progress

How to optimize metabolites concentrations and fluxes in a metabolic pathway? Backgrounds and Basics

The modelling of metabolic pathways is developed here for application to sugar metabolism of tomatoes during fruit expansion. In the now classic calculation of network fluxes, we add concentrations. Under assumptions of steady state and of "minimal effort" as proposed in [1], fluxes and concentrations, respecting constraints of experimental measurements and of thermodynamics, are searched. In order to obtain a well-posed problem, a preliminary mathematical study is in progress