Biochemistry · Enzyme
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) !
Recycles the bases hypoxanthine and guanine so they need not be built again; its loss causes Lesch-Nyhan syndrome.
Updated 2026-11-01
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Key facts
- Hypoxanthine + PRPP → IMP + PPi; guanine + PRPP → GMP + PPi.
- HPRT1 gene on the X chromosome: X-linked recessive inheritance.
- Complete deficiency: Lesch-Nyhan syndrome. Partial deficiency: hyperuricaemia and juvenile gout (Kelley-Seegmiller).
- It activates the prodrugs 6-mercaptopurine and 6-thioguanine (and azathioprine, via 6-mercaptopurine).
Memory aid
«HGPRT»: Hyperuricaemia, Gout, Pinching and biting (self-injury), Retardation, dysTonia.
Regulation
- No important allosteric regulation; its activity follows the supply of PRPP and bases.
Inhibitors and toxins
- Transition-state analogues (immucillin phosphates), experimental
Clinical notes
- Without HGPRT the bases are lost (more uric acid) and PRPP piles up, speeding de novo synthesis: a double cause of hyperuricaemia.
- Allopurinol controls the uric acid of Lesch-Nyhan syndrome but not its neurological symptoms.
- In the lab, HGPRT-negative cells survive 6-thioguanine and die in HAT medium: the basis of hybridoma selection.
Pathways
Related conditions
Related
- Hypoxanthine
- IMP (inosine monophosphate)
- PRPP (phosphoribosyl pyrophosphate)
- Adenine phosphoribosyltransferase (APRT)
- Xanthine oxidase
- Glutamine-PRPP amidotransferase
- Drugs acting on nucleotide metabolism
Test yourself
Think of the answer, then tap the question to see it.
Which reactions does HGPRT catalyse?
It joins hypoxanthine or guanine to PRPP, forming IMP or GMP; it is the main purine salvage route.
Why does HGPRT deficiency raise uric acid by two mechanisms?
Unrecycled bases are degraded to uric acid, and the spare PRPP speeds up de novo purine synthesis.
How is HGPRT related to 6-mercaptopurine?
HGPRT converts it to thio-IMP, its active form; without the enzyme the drug does not work.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: HPRT1: Hypoxanthine-guanine phosphoribosyltransferase (human) (UniProt, 2026); HPRT1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1HMP: THE CRYSTAL STRUCTURE OF HUMAN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE WITH BOUND GMP (RCSB Protein Data Bank, 2026); Purine salvage (Reactome, 2026).
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Representative model, for educational purposes only.