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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# PRPP synthetase

Makes PRPP, the activated ribose needed to build and recycle every nucleotide.

Updated 2026-11-01

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## Key facts

- Ribose-5-phosphate + ATP → PRPP + AMP, with Mg²⁺ and inorganic phosphate as activator.
- Its substrate comes from the pentose phosphate pathway.
- The PRPS1 gene is on the X chromosome: superactivity mainly affects males.
- Loss-of-function mutations cause a different picture: deafness, neuropathy or Arts syndrome.

**Also called**
Ribose-phosphate pyrophosphokinase

**EC number**
[2.7.6.1](https://www.enzyme-database.org/query.php?ec=2.7.6.1)

**Genes**
PRPS1, PRPS2

**Structure (PDB)**
[2HCR](https://www.rcsb.org/structure/2HCR)

## Regulation

- ADP and GDP inhibit it (nucleotide feedback).
- Inorganic phosphate activates it.

## Inhibitors and toxins

- ADP and GDP (physiological)

## Clinical notes

- PRPP synthetase superactivity: more PRPP, more purine synthesis, gout and uric acid stones in youth.
- The severe form of superactivity comes with deafness and developmental delay from infancy.

## Pathways

- [De novo purine synthesis](https://durgical.com/en/biochemistry/pathways/de-novo-purine-synthesis/)

## Related conditions

- [Gout](https://durgical.com/en/conditions/gout/)

## Related

- [PRPP (phosphoribosyl pyrophosphate)](https://durgical.com/en/biochemistry/molecules/prpp/)
- [Glutamine-PRPP amidotransferase](https://durgical.com/en/biochemistry/enzymes/glutamine-prpp-amidotransferase/)
- [Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)](https://durgical.com/en/biochemistry/enzymes/hypoxanthine-guanine-phosphoribosyltransferase/)
- [UMP synthase](https://durgical.com/en/biochemistry/enzymes/ump-synthase/)

## Test yourself

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## What does PRPP synthetase make, and what is it used for?

PRPP: it feeds de novo purine and pyrimidine synthesis, base salvage and NAD⁺ synthesis.

## Why does PRPP synthetase superactivity cause gout?

Extra PRPP drives the amidotransferase and purine synthesis, which end up as uric acid.

## How is PRPP synthetase superactivity inherited?

X-linked (PRPS1 gene): it mainly affects males.

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

Sources: [PRPS1: Ribose-phosphate pyrophosphokinase 1 (human)](https://www.uniprot.org/uniprotkb/P60891/entry) (UniProt, 2026); [Phosphoribosylpyrophosphate synthetase superactivity: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/phosphoribosylpyrophosphate-synthetase-superactivity/) (MedlinePlus, US National Library of Medicine, 2026); [PRPS1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/prps1/) (MedlinePlus, US National Library of Medicine, 2026); [2HCR: crystal structure of human phosphoribosyl pyrophosphate synthetase 1 in complex with AMP(ATP), cadmium and sulfate ion](https://www.rcsb.org/structure/2HCR) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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