Model number
0280

Salicylic acid (SA) clearance for three different dose ranges is modeled as an enzyme reaction. Model parameters are optimized and Monte-Carlo analysis is performed to robustly quantify parameter estimation, variance and covariance with other parameters in the presence of noisy data..

fig 1

Description

 This is an enzyme conversion model for salicylic acid clearance
 simultaneously fitting three independent data sets using shared parameters.
 The initial concentrations of salicylic acid range over almost two orders of
 magnitude.


         kon1->        koff2->     Gp->
  LSA+LE<-----> LSAE <-----> LE+LP-----> (Low Dose) 
         <-koff1        <-kon2


         kon1->        koff2->     Gp->
  MSA+ME<-----> MSAE <-----> ME+MP-----> (Mid Dose)
         <-koff1        <-kon2


         kon1->        koff2->     Gp->
  HSA+HE<-----> HSAE <-----> HE+HP-----> (Hi Dose)
         <-koff1        <-kon2

    koff1=KD1*kon1   koff2=KD2*kon1   

 where LSA, MSA, and HSA are Salicylic Acid concentrations,
 HE, ME, and HE are the free enzyme concentrations,
 LSAE, MSAE, and HSAE are salicylic acid-enzyme complex concentrations, and
 LP, MP, and HP are the product concentrations.

The parameters kon1, koff2, koff1, kon2, Gp, and the total amount of enzyme 
are the same for all three models. 

Equations

     Algebraic Equations

e0

e1

     Ordinary Differential and Mass Balance Equations

e2

e3

e4

e5

 

e6

e7

e8

e9

 

e10

e11

e12

e13

 

     Initial Conditions

e14 , e15 , e16 .

e17 , e18 , e19 .

The equations for this model may be viewed by running the JSim model applet and clicking on the Source tab at the bottom left of JSim's Run Time graphical user interface. The equations are written in JSim's Mathematical Modeling Language (MML). See the Introduction to MML and the MML Reference Manual. Additional documentation for MML can be found by using the search option at the Physiome home page.

Download JSim model project file

Help running a JSim model.

Key terms
aspirin
salicylic acid
Enzyme
clearance
covariance
confidence limits
optimization
Data
Tutorial
Monte-Carlo
Monte
Carlo
montecarlo
MonteCarlo
Monte Carlo
monte-carlo
Acknowledgements

Please cite https://www.imagwiki.nibib.nih.gov/physiome in any publication for which this software is used and send one reprint to the address given below:
The National Simulation Resource, Director J. B. Bassingthwaighte, Department of Bioengineering, University of Washington, Seattle WA 98195-5061.

Model development and archiving support at https://www.imagwiki.nibib.nih.gov/physiome provided by the following grants: NIH U01HL122199 Analyzing the Cardiac Power Grid, 09/15/2015 - 05/31/2020, NIH/NIBIB BE08407 Software Integration, JSim and SBW 6/1/09-5/31/13; NIH/NHLBI T15 HL88516-01 Modeling for Heart, Lung and Blood: From Cell to Organ, 4/1/07-3/31/11; NSF BES-0506477 Adaptive Multi-Scale Model Simulation, 8/15/05-7/31/08; NIH/NHLBI R01 HL073598 Core 3: 3D Imaging and Computer Modeling of the Respiratory Tract, 9/1/04-8/31/09; as well as prior support from NIH/NCRR P41 RR01243 Simulation Resource in Circulatory Mass Transport and Exchange, 12/1/1980-11/30/01 and NIH/NIBIB R01 EB001973 JSim: A Simulation Analysis Platform, 3/1/02-2/28/07.