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  • 1
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    Pathway analysis and optimization in metabolic engineering (2002)
    New York : Cambridge University Press
    Details
    Keywords: Biochemical engineering, Mathematical models. ; Mathematical optimization. ; System theory.
    Pages: xiv, 305 p.
    ISBN: 0-511-06322-9
    URL: http://www.netLibrary.com/urlapi.asp?action=summary&v=1&bookid=120551
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  • 2
    Electronic Resource
    Electronic Resource
    Transition time control analysis of a glycolytic system under different glucose concentrations. Control of transition time versus control of flux (1992)
    Springer
    Molecular and cellular biochemistry 112 (1992), S. 109-115 
    Details
    ISSN: 1573-4919
    Keywords: transition time ; flux ; metabolic control analysis ; glycolytis ; rat liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Control and Response Coefficients of transition time have been determined in a rat liver glycolytic system under different glucose concentrations. Results have been compared with the Flux Control and Flux Response Coefficients measured in the same conditions, showing that transition time and flux are different responses of the system, subject to different regulation and control. Control Coefficients of flux and transition time show a very different profile in each condition of glucose concentration assayed. Ratio of Flux Control coefficients of glucokinase over phosphofructokinase at 5 and 20 mM glucose concentration changes from 3.2 to 0.5, while the same ratio in the case of Transition Time Control Coefficients moves from 0.6 to 0.93. Moreover, the absolute values of Transition Time Control Coefficients in glycolytic conditions are one order of magnitude bigger than in gluconeogenic conditions. Values of Response Coefficients also show that the transition time has a bigger sensitivity to changes in glucose concentration than the flux in all conditions assayed, but particularly in glycolytic ones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227567
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  • 3
    Electronic Resource
    Electronic Resource
    Control analysis of rat liver glycolysis under different glucose concentrations. The substrate approach and the role of glucokinase (1992)
    Springer
    Molecular and cellular biochemistry 115 (1992), S. 1-9 
    Details
    ISSN: 1573-4919
    Keywords: control analysis ; response theorem ; glucose ; glucokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Control Analysis has been carried out in the first steps of a rat liver glycolytic system. Attention has been focused on the effect of several glucose concentrations on the control, particularly regarding the role of glucokinase. From kinetic studies of the whole metabolic system we have obtained information on the flux variation under different glucose concentrations. This information together with the kinetics of glucokinase has allowed us to calculate Flux Control and Elasticity Coefficients for glucokinase and the Response Coefficient of the system with respect to glucose. The changes in of the value of Flux Control Coefficients demonstrates that in conditions of low glucose concentration, glucokinase is the main enzyme in controlling the flux through the pathway, but at high glucose concentration the control moves to phosphofructokinase. Next, we have compared our results with those obtained with the shortening and titration method, previously described (Torres, N.V., Mateo, F., Mélendez-Hevia, E. and Kacser, H., (1986) Biochem. J. 234, 169–174; Torres, N.V. and Meléndez-Hevia, E. 1991. Molec. Cell. Biochem. 101, 1–10). Furthermore, from knowledge of the enzyme kinetics of the system we have been able to build a model of the pathway that allows us computer similation of its behavior and calculation of the Flux Control Coefficient profile at different glucose concentrations. By the three methods the results correlate, supporting the use of the pathway substrate as external modulator of the metabolic system as a tool for practical application of Control Analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229089
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  • 4
    Electronic Resource
    Electronic Resource
    Modelization and experimental studies on the control of the glycolytic-glycogenolytic pathway in rat liver (1994)
    Springer
    Molecular and cellular biochemistry 132 (1994), S. 117-126 
    Details
    ISSN: 1573-4919
    Keywords: flux ; metabolic control ; glycolysis ; rat liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract In this paper we construct a model of the glycolytic-glycogenolytic converging pathway in rat liver, by integrating experimental data obtained in anin vitro system and information available from the literature. The model takes the mathematical expression of an S-system representation within the power law formalism (Savageau, 1976. Biochemical System Analysis: A study of function and design in Molecular Biology. Addison-Wesley, Reading, Mass.). By using this theoretical framework a model analysis was carried out that allowed us a) the assessment of the quality of the model in terms of its consistency and robustness, b) the steady state analysis and control characterization of the system, and c) the study of the dynamics of the system after changes in the level of two magnitudes of biological significance: the glucose concentration and the phosphofructokinase enzyme activity. Model predictions are compared with experimental measurements referred to Logarithmic Gains through fluxes and substrates concentrations showing that there is a good correlation between the model predictions and the experimentally determined values.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00926920
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  • 5
    Electronic Resource
    Electronic Resource
    Detailed protocol and critical view for the analysis of control in metabolic systems by shortening and enzyme titration (1991)
    Springer
    Molecular and cellular biochemistry 101 (1991), S. 1-10 
    Details
    ISSN: 1573-4919
    Keywords: metabolic control ; control coefficients ; methodology ; enzyme titration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary In this paper we give a general description of the ‘shortening and enzyme titration method’. This method allows us to determine the Flux Control Coefficients of the different steps of a metabolic pathway in an in vitro experimental system. The system submitted to study is shortened in vitro by means of auxiliary enzymes, and the shortened pathway is titrated with extraneous enzymes. In this way we can modulate the activity of every enzyme of the system and thus every Flux Control Coefficient can be obtained. We criticise its different features in order to comment on the possibilities of its application to different types of systems. Our conclusion is that the method has a general applicability provided: a) that a correct definition of the metabolic pathway is given; b) that the system occurs in only one subcellular fraction and, c) that the dilution of the system by a given factor drives to the same reduction in every enzyme activity of the system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238432
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  • 6
    Electronic Resource
    Electronic Resource
    Control analysis of transition times (1991)
    Springer
    Molecular and cellular biochemistry 101 (1991), S. 83-91 
    Details
    ISSN: 1573-4919
    Keywords: transition times ; control analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary The present theoretical basis of Control Analysis is extended with the definition of Transition Time Response Coefficients. Some new relationships between local and global coefficients defined in Control Analysis are presented. These relationships are in the form of matrix products constructed in a priori form. The use of these straightforward relationships is shown in an exemplary application corresponding to an experimental system consisting of the glycolytic degradation from glucose to glyceraldehyde-3-phosphate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238441
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  • 7
    Electronic Resource
    Electronic Resource
    Control of glycolysis in rat liver by glucokinase and phosphofructokinase: influence of glucose concentration (1990)
    Springer
    Molecular and cellular biochemistry 93 (1990), S. 21-26 
    Details
    ISSN: 1573-4919
    Keywords: metabolic control ; glucose ; glycolysis ; rat liver ; glucokinase ; phosphofructokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Control of glucose metabolism in rat liver under different glucose concentrations was studied. Flux Control Coefficients of glucokinase, glucose 6-phosphate isomerase and phosphofructokinase were determined by the ‘shortening and enzyme titration’ method. Results obtained show that glucose concentration in liver can play an important role in control of liver glycolysis by enhancing the Flux Control Coefficient of phosphofructokinase. Possible physiological significance of this fact is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00223488
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  • 8
    Electronic Resource
    Electronic Resource
    Application of the transition time of metabolic system as a criterion for optimization of metabolic processes (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 44 (1994), S. 291-296 
    Details
    ISSN: 0006-3592
    Keywords: transition time ; control coefficients ; metabolic control analysis ; citric acid accumulation ; Aspergillu niger ; glycolysis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Transition time of metabolic systems in introduced as a suitable optimization criterion for biotechnological processes in which it is desirable to reduce the lag time and minimize the mass contained within the system. Lag time is the time needed for the system to attain the steady state. Results obtained from the sensitivity analysis of this steady state response are presented within the metabolic control analysis and applied to 3 case studies. In all of them the information provided by the transition time control profile allows the implementation of a strategy for biotechnological manipulations aimed at the improvement of the process. © 1994 John Wiley & Sons, Inc.
    Additional Material: 4 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260440306
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  • 9
    Electronic Resource
    Electronic Resource
    An indirect optimization method for biochemical systems: Description of method and application to the maximization of the rate of ethanol, glycerol, and carbohydrate production in Saccharomyces cerevisiae (1997)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 55 (1997), S. 758-772 
    Details
    ISSN: 0006-3592
    Keywords: Optimization ; metabolic systems ; linear programming ; S-system representation ; ethanol ; glycerol ; carbohydrates ; Saccharomyces cerevisiae ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Three metabolic models for the production of ethanol, glycerol, and carbohydrates in yeast are optimized with respect to different production rates. While originally nonlinear, all three optimization problems are reduced in such a way that methods of linear programming can be used. The optimizations lead to profiles of enzyme activities that are compatible with the physiology of the cells, which guarantees their viability and fitness, and yield higher rates of the desired final end products than the original systems. In order to increase ethanol rate production at least three times, six enzymes must be modulated. By contrast, when the production of glycerol or carbohydrates is optimized, modulation of just one enzyme (in the case of glycerol) or two enzymes (in the case of carbohydrates) is necessary to yield significant increases in product flux rate. Comparisons of our results with those obtained from other methods show great similarities and demonstrate that both are valid methods. The choice of one or the other method depends on the question of interest. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 758-772, 1997.
    Additional Material: 2 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    Optimization of nonlinear biotechnological processes with linear programming: Application to citric acid production by Aspergillus niger (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 49 (1996), S. 247-258 
    Details
    ISSN: 0006-3592
    Keywords: citric acid ; Aspergillus niger ; linear programming ; carbohydrate metabolism ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The metabolic pathway and the properties of many of the enzymes involved in the citric acid biosynthesis in the mold Aspergillus niger are well known. This fact, together with the availability of new theoretical frameworks aimed at quantitative analyses of control and dynamics in metabolic systems, has allowed us to construct a mathematical model of the carbohydrate metabolism in Aspergillus niger under conditions of citric acid accumulation. The model makes use of the S-system representation of biochemical systems, which renders it possible to use linear programming to optimize the process. It was found that maintaining the metabolite pools within narrow physiological limits (20% around the basal steady-state level) and allowing the enzyme concentrations to vary within a range of 0.1 to 50 times their basal values it is possible to triple the glycolytic flux while maintaining 100% yield of substrate transformation. To achieve these improvements it is necessary to modulate seven or more enzymes simultaneously. Although this seems difficult to implement at present, the results are useful because they indicate what the theoretical limits are and because they suggest several alternative strategies. © 1996 John Wiley & Sons, Inc.
    Additional Material: 1 Ill.
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