Hypoxanthine-guanine phosphoribosyltransferase (HPRT1) (HPRT1)

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme in the purine salvage pathway, facilitating the recycling of the purine bases hypoxanthine and guanine into their respective nucleotides, IMP and GMP (UniProt P00492; NCBI Gene 3251). This process is essential for maintaining cellular nucleotide pools and preventing the accumulation of uric acid, a byproduct of purine catabolism (StatPearls, Lesch Nyhan Syndrome). A complete deficiency of HGPRT activity results in Lesch-Nyhan syndrome, a severe metabolic disorder characterized by hyperuricemia, cognitive impairment, and self-injurious behavior, while partial deficiency leads to Kelley-Seegmiller syndrome and gout (NIH, Genetics Home Reference). In clinical practice, HGPRT is vital for the pharmacological activation of thiopurine drugs like 6-mercaptopurine and azathioprine, which are used to treat certain cancers and autoimmune conditions (PubChem, CID 667490). Because these drugs are converted into cytotoxic nucleotides by HGPRT, variations in enzyme activity can significantly impact both therapeutic efficacy and the risk of adverse effects such as bone marrow suppression (PubMed, PMID 25165114).

Other names

HGPRTHGPRTaseHypoxanthine phosphoribosyltransferase 1HPRT

Catalyzes the conversion of hypoxanthine to inosine monophosphate (IMP) and guanine to guanosine monophosphate (GMP) using 5-phosphoribosyl-1-pyrophosphate (PRPP) as a substrate (UniProt P00492). It also mediates the metabolic activation of thiopurine prodrugs into active cytotoxic thio-nucleotides (PubChem CID 667490).