Sensitivity of Blood Serum Uric Acid Concentration in HGPRT Deficiency to Initial Conditions of the Purine Metabolism Pathway

摘要

Purine metabolism is a fundamental component of the production of nucleotides, the building blocks of DNA and RNA. In this pathway, hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the conversion of phosphoribosylpyrophosphate to inosine monophosphate and to phosphorylated guanosine. Mild HGPRT deficiency can result in gout and mild hyperuricemia. More severe HGPRT deficiency can result in Lesch-Nyhan syndrome, characterized by spasticity, choreoathetosis, mental retardation, self-mutilation, renal failure, and in the most severe cases, death. For all but the simplest biochemical networks, empirical surveys of system behavior are intractable due to the large size of the state space, and simulation is the only general system-characterization method available. Here I present a simulator-oriented analysis of the sensitivity of blood serum uric acid concentration in HGPRT deficiency to initial conditions of the purine metabolism pathway. The results are consistent with clinical observations.