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.
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
Pathways
Related conditions
Related
- IMP (inosine monophosphate)
- Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
- Drugs acting on nucleotide metabolism
- NAD⁺ (nicotinamide adenine dinucleotide)
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).
Educational information, not medical advice. For any symptom, see a health professional.
Sources: IMPDH2: Inosine-5'-monophosphate dehydrogenase 2 (human) (UniProt, 2026); IMPDH1: Inosine-5'-monophosphate dehydrogenase 1 (human) (UniProt, 2026); 1NF7: Ternary complex of the human type II Inosine Monophosphate Dedhydrogenase with Ribavirin Monophosphate and C2-Mycophenolic Adenine Dinucleotide (RCSB Protein Data Bank, 2026); Mycophenolate: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.