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

# IMP dehydrogenase (IMPDH)

Opens the route from IMP to GMP; lymphocytes rely on it heavily, so mycophenolate blocks it to prevent rejection.

Updated 2026-11-01

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## Key facts

- IMP + NAD⁺ + H₂O → XMP + NADH; GMP synthetase then makes GMP.
- Rate-limiting step of guanine nucleotide synthesis; GMP inhibits it.
- IMPDH2 rises in activated lymphocytes and tumours; IMPDH1 predominates in the retina.
- Mycophenolic acid inhibits it uncompetitively, more potently for IMPDH2.

**EC number**
[1.1.1.205](https://www.enzyme-database.org/query.php?ec=1.1.1.205)

**Genes**
IMPDH1, IMPDH2

**Structure (PDB)**
[1NF7](https://www.rcsb.org/structure/1NF7)

## Regulation

- GMP: product inhibition.
- It forms highly active filaments when the cell needs a lot of GTP.

## Inhibitors and toxins

- Mycophenolic acid (mycophenolate)
- Ribavirin (as the monophosphate)
- Mizoribine

## Clinical notes

- Mycophenolate is used in transplantation and lupus nephritis: lymphocytes depend on de novo purine synthesis and stop.
- Ribavirin, an antiviral, lowers cellular GTP partly by inhibiting IMPDH.
- IMPDH1 variants cause dominant retinitis pigmentosa (RP10) and Leber congenital amaurosis.

## Drugs that act here

- [Ribavirin](https://durgical.com/en/pharmacology/ribavirin/)
- [Mycophenolate mofetil](https://durgical.com/en/pharmacology/mycophenolate-mofetil/)

## Pathways

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

## Related conditions

- [Systemic lupus erythematosus](https://durgical.com/en/conditions/systemic-lupus-erythematosus/)

## Related

- [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/)
- [NAD⁺ (nicotinamide adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/nad/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which reaction does IMPDH catalyse?

It oxidises IMP to XMP using NAD⁺; it is the first step towards GMP.

## Why does mycophenolate affect lymphocytes more than other cells?

Activated lymphocytes depend on de novo guanine synthesis (IMPDH2) and have little salvage; other cells recycle bases.

## Which eye disease is linked to IMPDH1 variants?

Autosomal dominant retinitis pigmentosa (RP10).

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

Sources: [IMPDH2: Inosine-5'-monophosphate dehydrogenase 2 (human)](https://www.uniprot.org/uniprotkb/P12268/entry) (UniProt, 2026); [IMPDH1: Inosine-5'-monophosphate dehydrogenase 1 (human)](https://www.uniprot.org/uniprotkb/P20839/entry) (UniProt, 2026); [1NF7: Ternary complex of the human type II Inosine Monophosphate Dedhydrogenase with Ribavirin Monophosphate and C2-Mycophenolic Adenine Dinucleotide](https://www.rcsb.org/structure/1NF7) (RCSB Protein Data Bank, 2026); [Mycophenolate: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a601081.html) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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