Fig. 1.

Scheme of the metabolic pathway of purines and their relation to hypoxanthine-guanine-phosphoribosyltransferase (HPRT). In Lesch–Nyhan disease (LND), the lack of HPRT activity leads to a failure in recycling of both guanine and hypoxanthine, thus creating a deficiency of both inosine monophosphate (IMP) and guanosine monophosphate (GMP). Hypoxanthine (and guanine) concentrations are elevated in LND and will be metabolized to uric acid by xanthine oxidase (XO). With S-adenosylmethionine (SAM, depicted in blue), an adenosine donor, the lack of purines in LND can be recovered by turning adenosine to adenosine monophosphate (AMP) by adenine phosphoribosyltransferase (APRT) and then to IMP. ADA adenosine deaminase, ADSL adenylosuccinate lyase, AK adenosine kinase, AMPRT amido phosphoribosyltransferase, ATP adenosine triphosphate, GTP guanosine triphosphate, IDH isocitrate dehydrogenase, PNP purine nucleoside phosphorylase, PPRP phosphoribosylpyrophosphate