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  • Introduction
  • Effects of Varying Rates and Pool Sizes - A Sample Program
  • Consideration of Multiple Compartments
  • Consideration of Cycles - The GS/GOGAT Cycle
  • Compounds Receiving Several 13C Atoms from 13CO2
  • Isotopomers of the Citric Acid Cycle Supplied with 3-13C-Pyruvate
  • Modeling Radioactive Precursor Uptake Kinetics
  • Simulation of The Pathway of DMSP Biosynthesis in Enteromorpha intestinalis
  • Simulation of The Pathway of Synthesis of DMSP in Spartina alterniflora
  • Making Rates Linearly or Hyperbolically Responsive to Pool Size Changes
  • Metabolic Engineering of Glycine Betaine Synthesis - Metabolism of 14C-Choline in Transgenic Tobacco Expressing Choline Monooxygenase in the Chloroplast
  • Considering Feedback Inhibition
  • Modeling Allosteric Behavior - Cooperative Substrate Binding
  • Links to Other Metabolic Modeling Resources on the www
  • References
  • Computer Simulation of Metabolism

    Consideration of Multiple Compartments

    As noted in the preceding pages, advantages of the iterative computer modeling approach over the kinetic equations described at the beginning of the Introduction, are that the iterative models can easily handle pulse-chase labeling kinetics and non-steady-state scenarios where pools expand or deplete with time as a result of imbalanced influxes and effluxes. In addition, the iterative computer models can easily accommodate multiple compartments where pools may be split between metabolically active ("met") and metabolically inactive or storage ("stor") components.

    Fig. 17, Fig. 18 and Fig. 19 illustrate an elaboration of the program described on the previous page, where the pools of intermediates B, C and D are envisaged to be partitioned between metabolically active ("met") and inactive or storage ("stor") compartments. Here, a number of adjustments must be made to both the Visual Basic Program Form and its objects (not shown), as well as to the underlying program code, including addition of several new variables:

  • B5, C5 and D5 = initial isotope abundance of the "storage" pools of B, C and D, respectively in units of atom %.

  • B6, C6 and D6 = initial pool sizes of the "storage" pools of B, C and D, respectively, in units of nmol.gfw-1.

  • B7, C7 and D7 = rates of transport of B, C and D from the "met" to the "stor" pools, respectively, in units of nmol.h-1.gfw-1.

    Note that this program plots the average isotope abundance of the two pools of B [i.e.((B1 * B2) + (B5 * B6)) / (B2 + B6)], C [i.e.((C1 * C2) + (C5 * C6)) / (C2 + C6)], and D [i.e.((D1 * D2) + (D5 * D6)) / (D2 + D6)], rather than the isotope abundance of only the metabolic pools (B1, C1, and D1, respectively). Moreover, the revised program plots the sum of the "met" + "stor" pools (i.e. B2 + B6, C2 + C6, and D2 + D6, respectively). Color codes used for Figures 17 to 19, below, are: (lower left graph panels, isotope abundance) A1 =black, average isotope abundance of pool B = green, average isotope abundance of total pool of C = blue, average isotope abundance of total pool of D = red; (lower right graph panels, pool sizes) B2 + B6 = green, C2 + C6 = blue, D2 + D6 = red.

    Fig. 17 shows simulations in which the "stor" pools of B, C, and D are each 100 nmol.gfw-1, and where transport rates from the "met" to the "stor" pools are small (B7 = 20 , C7 = 15 , D7 = 10 nmol.h-1.gfw-1). Note that the relatively slowly labeling "stor" pools each have a significant impact on isotopic labeling kinetics (compare Fig. 17 with Fig. 5 where similar rates and total pool sizes were assumed in the absence of any "stor" pools). As the "stor" pools are further increased to 300 nmol.gfw-1 each of B, C, and D at the expense of the "met" pools, the isotope dilution effects of these large storage pools are exaggerated (Fig. 18). In the case of pool B, where the "stor" pool is 50% of the total pool, labeling of the total pool of B is reduced by approximately one-half.

    The rate of transport of material between compartments also significantly affects the isotopic labeling kinetics; e.g. see Fig. 19, where the rate of transport of intermediate B from the "met" to the "stor" pool is increased 10-fold in comparison to Fig. 18.

    Download the Visual Basic program illustrated above. To run this program you must have Visual Basic 5.0 (or greater) installed on your computer.

    Download an enhanced version of this Visual Basic program capable of simulating "chase" stable isotope tracer kinetics, with rates expressed in minutes rather than hours, with adjustable graph axes, and with variable rates of transport both to and from the storage pools. To run this program you must have Visual Basic 5.0 (or greater) installed on your computer.

    Interactive client-side versions of the latter program are available in various formats that do not require Visual Basic:

  • VBScript, single-page. This interactive web page uses VBScript, and requires Microsoft Internet Explorer 3.0 or above to function. Note that this "client-side" program will not work with Netscape Navigator which does not support VBScript. This VBScript model produces simulated values in tabular rather than in graphical format, and expresses rates in units of minutes rather than hours.
  • VBScript, with 4 resizable frames. This interactive web page uses VBScript, and requires Microsoft Internet Explorer 3.0 or above to function. Note that this "client-side" program will not work with Netscape Navigator which does not support VBScript. This model provides a comparison of tabulated model output with an image of graphical output from a Visual Basic model using identical default starting values and assumptions. Rates are expressed in minutes rather than hours.
  • JavaScript, single-page. This JavaScript program should function with both Netscape Navigator and Microsoft Internet Explorer 3.0 or above. This JavaScript model produces simulated values in tabular rather than in graphical format, and expresses rates in units of minutes rather than hours.
  • JavaScript, with 4 resizable frames. This JavaScript program should function with both Netscape Navigator and Microsoft Internet Explorer 3.0 or above. This JavaScript model provides a comparison of tabulated model output with an image of graphical output from a Visual Basic model using identical default starting values and assumptions. Rates are expressed in minutes rather than hours.
  • Java applet, single-page. This applet should function with any Java-enabled browser, including Microsoft Internet Explorer 3.0 or above, or Netscape Navigator 3.0 or above. Output from the model is in graphical format, and time units are expressed in minutes rather than hours. "Definitions" of variables are provided in a resizable window.

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  • David Rhodes
    Department of Horticulture & Landscape Architecture
    Horticulture Building
    625 Agriculture Mall Drive
    Purdue University
    West Lafayette, IN 47907-2010
    Last Update: 8/20/03