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[Biochemistry](https://durgical.com/en/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

Loading the 3D model…

## 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.

**EC number**
[1.1.1.41](https://www.enzyme-database.org/query.php?ec=1.1.1.41)

**Genes**
IDH3A, IDH1, IDH2

**Structure (PDB)**
[1T0L](https://www.rcsb.org/structure/1T0L)

## 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

- [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/)

## Related conditions

- [Glioblastoma](https://durgical.com/en/conditions/glioblastoma/)

## Related

- [Citrate](https://durgical.com/en/biochemistry/molecules/citrate/)
- [NAD⁺ (nicotinamide adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/nad/)
- [α-Ketoglutarate dehydrogenase](https://durgical.com/en/biochemistry/enzymes/ketoglutarate-dehydrogenase/)

## 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⁺.

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

Sources: [IDH3A: Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial (human)](https://www.uniprot.org/uniprotkb/P50213/entry) (UniProt, 2026); [IDH1: Isocitrate dehydrogenase [NADP] cytoplasmic (human)](https://www.uniprot.org/uniprotkb/O75874/entry) (UniProt, 2026); [IDH1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/idh1/) (MedlinePlus, US National Library of Medicine, 2026); [1T0L: Human cytosolic NADP-dependent isocitrate dehydrogenase](https://www.rcsb.org/structure/1T0L) (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/isocitrate-dehydrogenase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/isocitrate-dehydrogenase/