Curto1998 - purine metabolism

ABSTRACT: Curto1998 - purine metabolism This is a purine metabolism model that is geared toward studies of gout. The model uses Generalized Mass Action (GMA; i.e. power law) descriptions of reaction rate laws. Such descriptions are local approximations that assume independent substrate binding. This model is described in the article: Mathematical models of purine metabolism in man. Curto R, Voit EO, Sorribas A, Cascante M. Math Biosci 1998 Jul; 151(1): 1-49 Abstract: Experimental and clinical data on purine metabolism are collated and analyzed with three mathematical models. The first model is the result of an attempt to construct a traditional kinetic model based on Michaelis-Menten rate laws. This attempt is only partially successful, since kinetic information, while extensive, is not complete, and since qualitative information is difficult to incorporate into this type of model. The data gaps necessitate the complementation of the Michaelis-Menten model with other functional forms that can incorporate different types of data. The most convenient and established representations for this purpose are rate laws formulated as power-law functions, and these are used to construct a Complemented Michaelis-Menten (CMM) model. The other two models are pure power-law-representations, one in the form of a Generalized Mass Action (GMA) system, and the other one in the form of an S-system. The first part of the paper contains a compendium of experimental data necessary for any model of purine metabolism. This is followed by the formulation of the three models and a comparative analysis. For physiological and moderately pathological perturbations in metabolites or enzymes, the results of the three models are very similar and consistent with clinical findings. This is an encouraging result since the three models have different structures and data requirements and are based on different mathematical assumptions. Significant enzyme deficiencies are not so well modeled by the S-system model. The CMM model captures the dynamics better, but judging by comparisons with clinical observations, the best model in this case is the GMA model. The model results are discussed in some detail, along with advantages and disadvantages of each modeling strategy. This model is hosted on BioModels Database and identified by: BIOMD0000000015. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Nicolas Le Novère  

PROVIDER: BIOMD0000000015 | BioModels | 2024-09-02

REPOSITORIES: BioModels