MM2Substrate_product_Inhibited

Model number
0321

  

Single enzyme irreversible Michaelis-Menten Eqs for Hx->Xa->Ua: Progress curves for xanthine oxidase reactions to oxidize hypoxanthine, Hx, to xanthine, Xa, to uric acid, Ua, and invokes inhibition by second product.(Data and equations from Escribano 1988).

Description

 Unidirectional fluxes Hx to Xa to Ua are facilitated 
 by a single enzyme, Xanthine Oxidase (EC# 1.7.3.2), in a hyperoxic medium at pH 8,
 so it is oxidative. Equations are Michaelis-Menten. The strategy is to have two models
 operating simultaneously, the first one to fit the data of Fig 4 (Hx->xa->Ua)
 Escribano88,  and the second to fit the data of Fig 5(Xa->Ua). Both models 
 use the identical parameters, The optimizer minimizes the RMS error for five (5)
 data curves at once, thereby providing an overall best estimate of the parameters.
 This strategy maximizes the ratio of data to parameters and narrows the confidence
 limits on the parameters.

 The inhibitory action of Ua was found by Escribano et al (1988) in a set of 
 inital velocity experiments, showing an apparent Ki, they report, of 178 uM,
 but no data were provided. As an exercise, set up this model to show a set of 
 initial consumptions of Xa at varied background levels of Ua. Alternatively, 
 add a new variable for tracer Ua to be produced from tracer Xa and show initial
 rates of production of tracer Ua.

Equations

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.

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References
 Bassingthwaighte James B., Chinn Tamara Meiko, Re-examining Michaelis-Menten
 enzyme kinetics for xanthine oxidase, Adv Physiol Educ 37: 37-48, 2013

 Escribano, J., Garcia-Canovas, F., and Garcia-Carmona,F.
 A kinetic study of hypoxanthine oxidation by milk xanthine oxidase.
 Biochem. J. 254:  829-833, 1988.

 Michaelis L and Menten ML. Die Kinetik der Invertinwirkung.
 Biochem Z 49: 333-369, 1913.
Key terms
purine nucleosides
xanthine oxidase
simple Michaelis-Menten equations
double reaction
serial reactions
progress curves
unidirectional
bovine milk
XO
Hx
Xa
Ua
hypoxanthine
xanthine
uric acid
saturable binding
data
publication
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.