Biochemistry · Enzyme
Isocitrate dehydrogenase !
Isocitrate dehydrogenase sets the pace of the Krebs cycle; its mutated relatives in some cancers make an oncometabolite.
Updated 2026-10-31
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Key facts
- Isocitrate + NAD⁺ → α-ketoglutarate + CO₂ + NADH; the cycle's rate-limiting step.
- In the cycle IDH3 (mitochondrial, NAD⁺) does the work. IDH1 (cytosol) and IDH2 (mitochondria) use NADP⁺ and make NADPH.
- The 3D model shows human IDH1 with isocitrate and NADP⁺: the active-site chemistry is the same.
Regulation
- ADP and Ca²⁺ activate it; ATP and NADH inhibit it.
Inhibitors and toxins
- Ivosidenib (mutant IDH1) and enasidenib (mutant IDH2): drugs against the mutant enzyme
Clinical notes
- IDH1/IDH2 mutations make the enzyme turn α-ketoglutarate into 2-hydroxyglutarate, which disturbs DNA methylation.
- They are found in many lower-grade gliomas and astrocytomas and in some acute myeloid leukemias; classic glioblastoma has no IDH mutation.
Pathways
Related conditions
Related
Test yourself
Think of the answer, then tap the question to see it.
Which IDH isoform works in the Krebs cycle?
IDH3, mitochondrial and NAD⁺-dependent.
Which oncometabolite do mutant IDH1/IDH2 make?
2-hydroxyglutarate (D-2HG).
What activates isocitrate dehydrogenase?
ADP and Ca²⁺.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: IDH3A: Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial (human) (UniProt, 2026); IDH1: Isocitrate dehydrogenase [NADP] cytoplasmic (human) (UniProt, 2026); IDH1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1T0L: Human cytosolic NADP-dependent isocitrate dehydrogenase (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.