Validation and steady-state analysis of a power-law model of purine metabolism in man.

The paper introduces a model of human purine metabolism in situ. Chosen from among several alternative system descriptions, the model is formulated as a Generalized Mass Action system within Biochemical Systems Theory and validated with analyses of steady-state and dynamic characteristics. Eigenvalue and sensitivity analyses indicate that the model has a stable and robust steady-state. The model quite accurately reproduces numerous biochemical and clinical observations in healthy subjects as well as in patients with disorders of purine metabolism. These results suggest that the model can be used to assess biochemical and clinical aspects of human purine metabolism. It provides a means of exploring eects of enzyme deficiencies and is a potential tool for identifying steps of the pathway that could be the target of therapeutical intervention. Numerous quan- titative comparisons with data are given. The model can be used for biomathematical exploration of relationships between enzymic deficiencies and clinically manifested diseases. the first kinetic models of purine metabolism based on data from dierent species and tissues, with the aim of demonstrating the usefulness of computer simulations of complex metabolic net- works. Heinmets (6) modelled nucleic acid synthesis from nucleo- tides and deoxynucleotides, although their parameters were not based on experimental data. More recently, Bartel and Holzhu$ tter (7) constructed a model based on rat liver as the reference system. The goal of the present paper goes beyond these earlier analyses. It is to analyse purine metabolism in the human body, to test the results against clinical observations, and to make predictions about the responses of patients with disorders of purine metab-