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

# Glutamine-PRPP amidotransferase

The main switch of purine synthesis: the committed step that turns off when there are enough nucleotides.

Updated 2026-11-01

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## Key facts

- PRPP + glutamine + H₂O → 5-phosphoribosylamine + glutamate + PPi.
- Committed, rate-limiting step of de novo purine synthesis.
- AMP, GMP and IMP inhibit it (synergistic inhibition); PRPP activates it and shifts it out of its inactive form.
- One domain hydrolyses glutamine and sends NH₃ through a tunnel to the PRPP site.

**Also called**
Amidophosphoribosyltransferase

**EC number**
[2.4.2.14](https://www.enzyme-database.org/query.php?ec=2.4.2.14)

**Genes**
PPAT

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

## Regulation

- AMP, GMP and IMP: feedback inhibition.
- PRPP: substrate activation.

## Inhibitors and toxins

- Azaserine and 6-diazo-5-oxo-norleucine (DON), glutamine analogues
- Thio-IMP and methylthio-IMP (from 6-mercaptopurine)

## Clinical notes

- Excess PRPP (PRPP synthetase superactivity, HGPRT deficiency) over-activates it and raises uric acid.
- Metabolites of 6-mercaptopurine and azathioprine inhibit it as if they were the cell's own nucleotides.

## Pathways

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

## Related conditions

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

## Related

- [PRPP (phosphoribosyl pyrophosphate)](https://durgical.com/en/biochemistry/molecules/prpp/)
- [PRPP synthetase](https://durgical.com/en/biochemistry/enzymes/prpp-synthetase/)
- [IMP (inosine monophosphate)](https://durgical.com/en/biochemistry/molecules/imp/)
- [Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)](https://durgical.com/en/biochemistry/enzymes/hypoxanthine-guanine-phosphoribosyltransferase/)
- [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 step of purine synthesis does the amidotransferase catalyse?

The first step unique to the pathway (committed): it moves glutamine nitrogen onto PRPP, forming phosphoribosylamine.

## Which end products inhibit the amidotransferase?

AMP, GMP and IMP; the effect is stronger when both adenine and guanine nucleotides are present.

## Why does HGPRT deficiency speed this enzyme up?

Without salvage there is spare PRPP, its activator, and less IMP and GMP, its brakes.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/biochemistry/enzymes/glutamine-prpp-amidotransferase/)

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

Sources: [PPAT: Amidophosphoribosyltransferase (human)](https://www.uniprot.org/uniprotkb/Q06203/entry) (UniProt, 2026); [Purine ribonucleoside monophosphate biosynthesis](https://reactome.org/PathwayBrowser/#/R-HSA-73817) (Reactome, 2026); [1ECC: ESCHERICHIA COLI GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE (PRPP) AMIDOTRANSFERASE COMPLEXED WITH MN-CPRPP AND 5-OXO-NORLEUCINE](https://www.rcsb.org/structure/1ECC) (RCSB Protein Data Bank, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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