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 effects of enzyme deficiencies and is a potential tool for identifying steps of the pathway that could be the target of therapeutical intervention. Numerous quantitative comparisons with data are given. The model can be used for biomathematical exploration of relationships between enzymic deficiencies and clinically manifested diseases.
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Departament de Bioquímica i Biología Molecular, Facultat de Químiques, Universitat de Barcelona, 08028 Barcelona, Catalunya, Spain.
Voit
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Sorribas
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Cascante
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D000225:Adenine / Q000378:metabolism; D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency; D006147:Guanine / Q000378:metabolism; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D007700:Kinetics; D008954:Models, Biological; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014527:Uric Acid / Q000378:metabolism; D019820:Xanthine; D014970:Xanthines / Q000652:urine
D011687:Purines; D014970:Xanthines; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D006147:Guanine; D010754:Phosphoribosyl Pyrophosphate; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D000225:Adenine