Fig. 1

Purine metabolism in Lesch-Nyhan disease (LND) and cell culture media composition. A Scheme of the de novo and salvage pathways of purine nucleotide biosynthesis. The deficiency of HGprt enzyme in LND increases the levels of guanine, hypoxanthine, and PRPP and accelerates the de novo pathway producing high levels of uric acid. Adenine phosphoribosyltransferase (APRT) catalyses the synthesis of AMP from PRPP and adenine. There are two enzymes in the de novo pathway that incorporate 10-formyltetrahydrofolate: GAR transformylase (GART), and 5-aminoimidazole-4-carboxamide ribotide transformylase-IMP cyclohydrolase (ATIC). ZMP can inhibit the bifunctional enzyme adenylosuccinate lyase (ADSL), induce AMP-activated protein kinase (AMPK) activation and mitochondrial dysfunction. B, C Formulations of Roswell Park Memorial Institute (RPMI) medium 1640, Human Plasma-Like Medium (HPLM) and Plasmax with physiological vitamins (Plasmax-PV). Vitamin concentrations are expressed in nM (B), whereas the concentrations of other important components are in μM (C). NA not available