/*
 * In situ kinetic analysis of glyoxalase I and glyoxalase II in
 * Saccharomyces cerevisiae
 * 
 * Model Status
 * 
 * This model runs in both OpenCell and COR but does not replicate
 * the published results - probably because the publication does
 * not define the substate HTA. The units have been checked and
 * they are consistent.
 * 
 * Model Structure
 * 
 * ABSTRACT: The kinetics of glyoxalase I [(R)-S-lactoylglutathione
 * methylglyoxal-lyase; EC 4.4.1.5] and glyoxalase II (S-2-hydroxyacylglutathione
 * hydrolase; EC 3.1.2.6) from Saccharomyces cerevisiae was studied
 * in situ, in digitonin permeabilized cells, using two different
 * approaches: initial rate analysis and progress curves analysis.
 * Initial rate analysis was performed by hyperbolic regression
 * of initial rates using the program HYPERFIT. Glyoxalase I exhibited
 * saturation kinetics on 0.05-2.5 mM hemithioacetal concentration
 * range, with kinetic parameters Km 0.53 +/- 0.07 mM and V (3.18
 * +/- 0.16) x 10(-2) mM.min(-1). Glyoxalase II also showed saturation
 * kinetics in the SD-lactoylglutathione concentration range of
 * 0.15-3 mM and Km 0.32 +/- 0.13 mM and V (1.03 +/- 0.10) x 10(-3)
 * mM.min(-1) were obtained. The kinetic parameters of both enzymes
 * were also estimated by nonlinear regression of progress curves
 * using the raw absorbance data and integrated differential rate
 * equations with the program GEPASI. Several optimization methods
 * were used to minimize the sum of squares of residuals. The best
 * parameter fit for the glyoxalase I reaction was obtained with
 * a single curve analysis, using the irreversible Michaelis-Menten
 * model. The kinetic parameters obtained, Km 0.62 +/- 0.18 mM
 * and V (2.86 +/- 0.01) x 10(-2) mM.min(-1), were in agreement
 * with those obtained by initial rate analysis. The results obtained
 * for glyoxalase II, using either the irreversible Michaelis-Menten
 * model or a phenomenological reversible hyperbolic model, showed
 * a high correlation of residuals with time and/or high values
 * of standard deviation associated with Km. The possible causes
 * for the discrepancy between data obtained from initial rate
 * analysis and progress curve analysis, for glyoxalase II, are
 * discussed.
 * 
 * The original paper reference is cited below:
 * 
 * In situ kinetic analysis of glyoxalase I and glyoxalase II in
 * Saccharomyces cerevisiae, Margarida Martins, A. et al, 2001,
 * European Journal of Biochemistry, 268, 3930-3936. PubMed ID:
 * 11453985
 * 
 * [[Image file: margarida_2001.png]]
 * 
 * A rendering of the glyoxalase pathway. Species are represented
 * by rounded rectangles, and reactions by arrows. The action of
 * a catalyst on a reaction is represented by dashed lines.
 */

import nsrunit;
unit conversion on;
unit minute=60 second^1;
// unit millimolar predefined
unit flux=.01666667 meter^(-3)*second^(-1)*mole^1;

math main {
	realDomain time minute;
	time.min=0;
	extern time.max;
	extern time.delta;
	real GSH(time) millimolar;
	when(time=time.min) GSH=1.0;
	real GSH.V flux;
	GSH.V=3.44E-3;
	real GSH.Kms millimolar;
	GSH.Kms=0.49;
	real GSH.Kmp millimolar;
	GSH.Kmp=0.49;
	real Kmq millimolar;
	Kmq=0.49;
	real GSH.Keq millimolar;
	GSH.Keq=0.49;
	real SDLGSH(time) millimolar;
	when(time=time.min) SDLGSH=1.0;
	real D_lactate millimolar;
	D_lactate=0.0;
	real HTA millimolar;
	HTA=1.0;
	real SDLGSH.V flux;
	SDLGSH.V=8.12E-2;
	real SDLGSH.Kms millimolar;
	SDLGSH.Kms=0.61;
	real SDLGSH.Kmp millimolar;
	SDLGSH.Kmp=0.61;
	real SDLGSH.Keq dimensionless;
	SDLGSH.Keq=0.61;

	// <component name="environment">

	// <component name="GSH">
	GSH:time=(GSH.V/GSH.Kms*(SDLGSH-GSH*D_lactate/GSH.Keq)/(1+SDLGSH/GSH.Kms+GSH/GSH.Kmp+D_lactate/Kmq));

	// <component name="HTA">

	// <component name="SDLGSH">
	SDLGSH:time=(SDLGSH.V/SDLGSH.Kms*(HTA-SDLGSH/SDLGSH.Keq)/(1+HTA/SDLGSH.Kms+SDLGSH/SDLGSH.Kmp));

	// <component name="D_lactate">
}