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  1. Article ; Online: A Theoretical Model of Mitochondrial ATP Synthase Deficiencies. The Role of Mitochondrial Carriers

    Jean-Pierre Mazat / Anne Devin / Edgar Yoboue / Stéphane Ransac

    Processes, Vol 9, Iss 1424, p

    2021  Volume 1424

    Abstract: The m.8993T>G mutation of the mitochondrial MT-ATP6 gene is associated with NARP syndrome (neuropathy, ataxia and retinitis pigmentosa). The equivalent point mutation introduced in yeast Saccharomyces cerevisiae mitochondrial DNA considerably reduced the ...

    Abstract The m.8993T>G mutation of the mitochondrial MT-ATP6 gene is associated with NARP syndrome (neuropathy, ataxia and retinitis pigmentosa). The equivalent point mutation introduced in yeast Saccharomyces cerevisiae mitochondrial DNA considerably reduced the activity of ATP synthase and of cytochrome-c-oxidase, preventing yeast growth on oxidative substrates. The overexpression of the mitochondrial oxodicarboxylate carrier (Odc1p) was able to rescue the growth on the oxidative substrate by increasing the substrate-level phosphorylation of ADP coupled to the conversion of α -ketoglutarate (AKG) into succinate with an increase in Complex IV activity. Previous studies showed that equivalent point mutations in ATP synthase behave similarly and can be rescued by Odc1p overexpression and/or the uncoupling of OXPHOS from ATP synthesis. In order to better understand the mechanism of the ATP synthase mutation bypass, we developed a core model of mitochondrial metabolism based on AKG as a respiratory substrate. We describe the different possible metabolite outputs and the ATP/O ratio values as a function of ATP synthase inhibition.
    Keywords mitochondrial metabolism ; metabolic model ; ATP/O ; substrate-level phosphorylation ; Odc1 ; Chemical technology ; TP1-1185 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: FluxVisualizer, a Software to Visualize Fluxes through Metabolic Networks

    Tim Daniel Rose / Jean-Pierre Mazat

    Processes, Vol 6, Iss 5, p

    2018  Volume 39

    Abstract: FluxVisualizer (Version 1.0, 2017, freely available at https://fluxvisualizer.ibgc.cnrs.fr) is a software to visualize fluxes values on a scalable vector graphic (SVG) representation of a metabolic network by colouring or increasing the width of reaction ...

    Abstract FluxVisualizer (Version 1.0, 2017, freely available at https://fluxvisualizer.ibgc.cnrs.fr) is a software to visualize fluxes values on a scalable vector graphic (SVG) representation of a metabolic network by colouring or increasing the width of reaction arrows of the SVG file. FluxVisualizer does not aim to draw metabolic networks but to use a customer’s SVG file allowing him to exploit his representation standards with a minimum of constraints. FluxVisualizer is especially suitable for small to medium size metabolic networks, where a visual representation of the fluxes makes sense. The flux distribution can either be an elementary flux mode (EFM), a flux balance analysis (FBA) result or any other flux distribution. It allows the automatic visualization of a series of pathways of the same network as is needed for a set of EFMs. The software is coded in python3 and provides a graphical user interface (GUI) and an application programming interface (API). All functionalities of the program can be used from the API and the GUI and allows advanced users to add their own functionalities. The software is able to work with various formats of flux distributions (Metatool, CellNetAnalyzer, COPASI and FAME export files) as well as with Excel files. This simple software can save a lot of time when evaluating fluxes simulations on a metabolic network.
    Keywords metabolic network visualization ; metabolic modelling ; elementary flux modes visualization ; flux balance analysis ; Chemical technology ; TP1-1185 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Modeling the respiratory chain complexes with biothermokinetic equations — The case of complex I

    Heiske, Margit / Christine Nazaret / Jean-Pierre Mazat

    Biochimica et biophysica acta. 2014 Oct., v. 1837, no. 10

    2014  

    Abstract: The mitochondrial respiratory chain plays a crucial role in energy metabolism and its dysfunction is implicated in a wide range of human diseases. In order to understand the global expression of local mutations in the rate of oxygen consumption or in the ...

    Abstract The mitochondrial respiratory chain plays a crucial role in energy metabolism and its dysfunction is implicated in a wide range of human diseases. In order to understand the global expression of local mutations in the rate of oxygen consumption or in the production of adenosine triphosphate (ATP) it is useful to have a mathematical model in which the changes in a given respiratory complex are properly modeled. Our aim in this paper is to provide thermodynamics respecting and structurally simple equations to represent the kinetics of each isolated complexes which can, assembled in a dynamical system, also simulate the behavior of the respiratory chain, as a whole, under a large set of different physiological and pathological conditions. On the example of the reduced nicotinamide adenine dinucleotide (NADH)–ubiquinol–oxidoreductase (complex I) we analyze the suitability of different types of rate equations. Based on our kinetic experiments we show that very simple rate laws, as those often used in many respiratory chain models, fail to describe the kinetic behavior when applied to a wide concentration range. This led us to adapt rate equations containing the essential parameters of enzyme kinetic, maximal velocities and Henri–Michaelis–Menten like-constants (KM and KI) to satisfactorily simulate these data.
    Keywords NAD (coenzyme) ; adenosine triphosphate ; electron transport chain ; enzyme kinetics ; equations ; human diseases ; mathematical models ; mitochondria ; mutation ; oxygen consumption ; thermodynamics
    Language English
    Dates of publication 2014-10
    Size p. 1707-1716.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 282711-6
    ISSN 0005-2728 ; 0304-4173
    ISSN 0005-2728 ; 0304-4173
    DOI 10.1016/j.bbabio.2014.07.013
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Victor Henri: 111 years of his equation

    Cornish-Bowden, Athel / Jean-Pierre Mazat / Serge Nicolas

    Biochimie. 2014 Dec., v. 107

    2014  

    Abstract: Victor Henri's great contribution to the understanding of enzyme kinetics and mechanism is not always given the credit that it deserves. In addition, his earlier work in experimental psychology is totally unknown to biochemists, and his later work in ... ...

    Abstract Victor Henri's great contribution to the understanding of enzyme kinetics and mechanism is not always given the credit that it deserves. In addition, his earlier work in experimental psychology is totally unknown to biochemists, and his later work in spectroscopy and photobiology almost equally so. Applying great rigour to his analysis he succeeded in obtaining a model of enzyme action that explained all of the observations available to him, and he showed why the considerable amount of work done in the preceding decade had not led to understanding. His view was that only physical chemistry could explain the behaviour of enzymes, and that models should be judged in accordance with their capacity not only to explain previously known facts but also to predict new observations against which they could be tested. The kinetic equation usually attributed to Michaelis and Menten was in reality due to him. His thesis of 1903 is now available in English.
    Keywords enzyme kinetics ; enzymes ; equations ; models ; photobiology ; physical chemistry ; psychology ; spectroscopy
    Language English
    Dates of publication 2014-12
    Size p. 161-166.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 120345-9
    ISSN 0300-9084
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2014.09.018
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Research data: (with research data) Model-Assisted Analysis of Sugar Metabolism throughout Tomato Fruit Development Reveals Enzyme and Carrier Properties in Relation to Vacuole Expansion

    Beauvoit, Bertrand P / Antoine Monier / Benoit Biais / Camille Bénard / Catherine Chéniclet / Christine Nazaret / Jean-Pierre Mazat / Marie-Hélène Andrieu / Martine Dieuaide-Noubhani / Sophie Colombié / Yves Gibon

    plant cell. 2014 Aug., v. 26, no. 8

    2014  

    Abstract: A kinetic model combining enzyme activities and subcellular compartmentation was built to analyze the storage and interconversion of sugars in developing tomato fruit. This work shows that tonoplast carriers, sucrose hydrolysis, and accumulation of ... ...

    Abstract A kinetic model combining enzyme activities and subcellular compartmentation was built to analyze the storage and interconversion of sugars in developing tomato fruit. This work shows that tonoplast carriers, sucrose hydrolysis, and accumulation of organic acids are major contributors to the vacuole expansion and the metabolic reprogramming that occur during early development.

    A kinetic model combining enzyme activity measurements and subcellular compartmentation was parameterized to fit the sucrose, hexose, and glucose-6-P contents of pericarp throughout tomato ( Solanum lycopersicum ) fruit development. The model was further validated using independent data obtained from domesticated and wild tomato species and on transgenic lines. A hierarchical clustering analysis of the calculated fluxes and enzyme capacities together revealed stage-dependent features. Cell division was characterized by a high sucrolytic activity of the vacuole, whereas sucrose cleavage during expansion was sustained by both sucrose synthase and neutral invertase, associated with minimal futile cycling. Most importantly, a tight correlation between flux rate and enzyme capacity was found for fructokinase and PPi-dependent phosphofructokinase during cell division and for sucrose synthase, UDP-glucopyrophosphorylase, and phosphoglucomutase during expansion, thus suggesting an adaptation of enzyme abundance to metabolic needs. In contrast, for most enzymes, flux rates varied irrespectively of enzyme capacities, and most enzymes functioned at <5% of their maximal catalytic capacity. One of the major findings with the model was the high accumulation of soluble sugars within the vacuole together with organic acids, thus enabling the osmotic-driven vacuole expansion that was found during cell division.
    Keywords early development ; enzyme activity ; fruiting ; hydrolysis ; kinetics ; metabolism ; organic acids and salts ; sucrose ; tomatoes ; tonoplast ; vacuoles
    Language English
    Dates of publication 2014-08
    Size p. 3224-3242.
    Publishing place American Society of Plant Biologists
    Document type Article ; Research data
    ZDB-ID 623171-8
    ISSN 1532-298X ; 1040-4651 ; 1040-4651
    ISSN (online) 1532-298X
    ISSN 1040-4651
    DOI 10.1105/tpc.114.127761
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Remarkable Reproducibility of Enzyme Activity Profiles in Tomato Fruits Grown under Contrasting Environments Provides a Roadmap for Studies of Fruit Metabolism

    Biais, Benoît / Bernadette Gehl / Bertrand Beauvoit / Camille Bénard / Duyên Prodhomme / Guillaume Ménard / Hélène Gautier / Jean-Pierre Mazat / Lee Sweetlove / Michel Génard / Patricia Ballias / Sophie Colombié / Stéphane Bernillon / Yves Gibon

    Plant physiology. 2014 Mar., v. 164, no. 3

    2014  

    Abstract: Enzyme activities in central metabolism of tomato fruits are strongly influenced by developmental stage but only weakly by environment . ...

    Abstract Enzyme activities in central metabolism of tomato fruits are strongly influenced by developmental stage but only weakly by environment .
    Keywords enzyme activity ; fruits ; metabolism ; tomatoes
    Language English
    Dates of publication 2014-03
    Size p. 1204-1221.
    Publishing place American Society of Plant Biologists
    Document type Article
    ZDB-ID 208914-2
    ISSN 1532-2548 ; 0032-0889
    ISSN (online) 1532-2548
    ISSN 0032-0889
    DOI 10.1104/pp.113.231241
    Database NAL-Catalogue (AGRICOLA)

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