[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

[Biochemistry](https://durgical.com/en/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.

**EC number**
[2.4.2.8](https://www.enzyme-database.org/query.php?ec=2.4.2.8)

**Genes**
HPRT1

**Structure (PDB)**
[1HMP](https://www.rcsb.org/structure/1HMP)

## 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

- [Purine degradation and salvage](https://durgical.com/en/biochemistry/pathways/purine-degradation-and-salvage/)

## Related conditions

- [Lesch-Nyhan syndrome](https://durgical.com/en/conditions/lesch-nyhan-syndrome/)
- [Gout](https://durgical.com/en/conditions/gout/)
- [Kidney stones (urolithiasis)](https://durgical.com/en/conditions/kidney-stones/)

## Related

- [Hypoxanthine](https://durgical.com/en/biochemistry/molecules/hypoxanthine/)
- [IMP (inosine monophosphate)](https://durgical.com/en/biochemistry/molecules/imp/)
- [PRPP (phosphoribosyl pyrophosphate)](https://durgical.com/en/biochemistry/molecules/prpp/)
- [Adenine phosphoribosyltransferase (APRT)](https://durgical.com/en/biochemistry/enzymes/adenine-phosphoribosyltransferase/)
- [Xanthine oxidase](https://durgical.com/en/biochemistry/enzymes/xanthine-oxidase/)
- [Glutamine-PRPP amidotransferase](https://durgical.com/en/biochemistry/enzymes/glutamine-prpp-amidotransferase/)
- [Drugs acting on nucleotide metabolism](https://durgical.com/en/biochemistry/topics/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [HPRT1: Hypoxanthine-guanine phosphoribosyltransferase (human)](https://www.uniprot.org/uniprotkb/P00492/entry) (UniProt, 2026); [HPRT1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/hprt1/) (MedlinePlus, US National Library of Medicine, 2026); [1HMP: THE CRYSTAL STRUCTURE OF HUMAN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE WITH BOUND GMP](https://www.rcsb.org/structure/1HMP) (RCSB Protein Data Bank, 2026); [Purine salvage](https://reactome.org/PathwayBrowser/#/R-HSA-74217) (Reactome, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/hypoxanthine-guanine-phosphoribosyltransferase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/hypoxanthine-guanine-phosphoribosyltransferase/