title: Analysis of abnormalities in purine metabolism leading to gout and to neurological dysfunctions in man.
abstract: A modelling approach is used to analyse diseases associated with purine metabolism in man. The specific focus is on deficiencies in two enzymes, hypoxanthine:guanine phosphoribosyltransferase and adenylosuccinate lyase. These deficiencies can lead to a number of symptoms, including neurological dysfunctions and mental retardation. Although the biochemical mechanisms of dysfunctions associated with adenylosuccinate lyase deficiency are not completely understood, there is at least general agreement in the literature about possible causes. Simulations with our model confirm that accumulation of the two substrates of the enzyme can lead to significant biochemical imbalance. In hypoxanthine:guanine phosphoribosyltransferase deficiency the biochemical mechanisms associated with neurological dysfunctions are less clear. Model analyses support some old hypotheses but also suggest new indicators for possible causes of neurological dysfunctions associated with this deficiency. Hypoxanthine:guanine phosphoribosyltransferase deficiency is known to cause hyperuricaemia and gout. We compare the relative importance of this deficiency with other known causes of gout in humans. The analysis suggests that defects in the excretion of uric acid are more consequential than defects in uric acid synthesis such as hypoxanthine:guanine phosphoribosyltransferase deficiency.
authors.affiliation: Departament de Bioquimica i Biologia Molecular, Facultat de Quimiques, Universitat de Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Curto
authors.forename: E O
authors.initials: EO
authors.lastname: Voit
authors.forename: M
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000659:AMP Deaminase / Q000378:metabolism; D000264:Adenylosuccinate Lyase / Q000172:deficiency; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000378:metabolism; D006073:Gout / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics; D007926:Lesch-Nyhan Syndrome / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008956:Models, Chemical; D011687:Purines / Q000378:metabolism*; D012265:Ribonucleotides / Q000378:metabolism; D012268:Ribose-Phosphate Pyrophosphokinase / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
chemical_list: D011687:Purines; D012265:Ribonucleotides; D014527:Uric Acid; D000620:Aminoimidazole Carboxamide; D007041:Hypoxanthine Phosphoribosyltransferase; D012268:Ribose-Phosphate Pyrophosphokinase; D000659:AMP Deaminase; D000264:Adenylosuccinate Lyase; C020635:SAICAR; C030985:purine