Figure 1

Purine metabolism. The metabolic scheme shows the first and rate-limiting step of de novo purine synthesis mediated by the enzyme 5'-phosphoribosyl-1-pyrophosphate (PRPP) amidotransferase, and the salvage pathway mediated by hypoxanthine phosphorybosyltransferase (HPRT) and adenine phosphorybosyltransferase (APRT). The de novo synthesis occurs through a multi-step process and requires the contribution of four aminoacids, one PRPP, two folates and three ATP to synthesize an inosine monophosphate (IMP) molecule. HPRT catalyzes the salvage synthesis of inosine monophosphate (IMP) and guanosine monophosphate (GMP) from the purine bases hypoxanthine and guanine respectively, utilizing PRPP as a co-substrate. The HPRT defect results in the accumulation of its substrates, hypoxanthine and guanine, which are converted into uric acid by means of xanthine oxidase. Elevated APRT activity may also contribute to purine overproduction.