Hypoxanthine-guanine phosphoribosyltransferase

HPRT1 (hypoxanthine-guanine phosphoribosyltransferase) catalyzes the salvage of purine nucleotides by converting guanine to GMP and hypoxanthine to IMP, transferring the 5-phosphoribosyl group from PRPP in this essential biosynthetic pathway (UniProt: P00492). The enzyme is predominantly expressed in tissues with high nucleotide turnover. Mutations in HPRT1 cause Lesch-Nyhan syndrome (MIM 300322), a severe X-linked disorder marked by complete enzymatic loss and resulting hyperuricemia, neurological dysfunction, and self-injurious behavior, as well as HPRT-related hyperuricemia (MIM 300323).

In Alzheimer's disease, HPRT1 is downregulated in post-mortem AD brain tissue relative to age-matched controls (mean log2FC −0.59), based on TMT-labeled quantitative proteomics across four subcellular fractions (Chaparral AD proteomics). This reduction suggests compromised purine salvage capacity in AD pathology, though the functional consequence of diminished HPRT1 in neurodegeneration remains to be clarified.