[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Pyruvate dehydrogenase complex (PDH)

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

# Pyruvate dehydrogenase complex (PDH)

Pyruvate dehydrogenase is the gate between glycolysis and the Krebs cycle; it needs five coenzymes and four B vitamins.

Updated 2026-10-31

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## Key facts

- Pyruvate + CoA + NAD⁺ → acetyl-CoA + CO₂ + NADH; irreversible.
- Three enzymes in one giant complex: E1 (with thiamine pyrophosphate), E2 (with lipoic acid, adds CoA) and E3 (with FAD, regenerates lipoate and reduces NAD⁺).
- Coenzymes: thiamine pyrophosphate (B1), lipoic acid, CoA (B5), FAD (B2), NAD⁺ (B3).
- E3 is shared with α-ketoglutarate dehydrogenase and the branched-chain keto acid dehydrogenase.

**EC number**
[1.2.4.1](https://www.enzyme-database.org/query.php?ec=1.2.4.1)

**Genes**
PDHA1, PDHB, DLAT, DLD

**Structure (PDB)**
[1NI4](https://www.rcsb.org/structure/1NI4)

## Regulation

- Its products (acetyl-CoA, NADH) inhibit it.
- PDH kinase phosphorylates and switches it off; PDH phosphatase (Ca²⁺, insulin) switches it back on. Dichloroacetate inhibits the kinase.

## Inhibitors and toxins

- Arsenite and other compounds that trap lipoic acid
- Thiamine lack

## Clinical notes

- PDH deficiency (usually PDHA1, X-linked) causes lactic acidosis with a normal lactate/pyruvate ratio and Leigh syndrome.
- The ketogenic diet gives the brain a fuel that bypasses PDH.
- Giving glucose without thiamine to a malnourished patient can trigger Wernicke encephalopathy.

## Pathways

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

## Related conditions

- [Pyruvate dehydrogenase deficiency](https://durgical.com/en/conditions/pyruvate-dehydrogenase-deficiency/)
- [Wernicke encephalopathy (thiamine deficiency)](https://durgical.com/en/conditions/wernicke-encephalopathy/)
- [Arsenic poisoning](https://durgical.com/en/conditions/arsenic-poisoning/)
- [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/)

## Related

- [Pyruvate](https://durgical.com/en/biochemistry/molecules/pyruvate/)
- [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/)
- [α-Ketoglutarate dehydrogenase](https://durgical.com/en/biochemistry/enzymes/ketoglutarate-dehydrogenase/)
- [NAD⁺ (nicotinamide adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/nad/)

## Test yourself

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

## What are PDH's five coenzymes?

Thiamine pyrophosphate, lipoic acid, coenzyme A, FAD and NAD⁺.

## How is PDH switched off when energy is plentiful?

PDH kinase phosphorylates it; ATP, NADH and acetyl-CoA activate that kinase.

## Why is thiamine given before glucose to a patient with alcohol use disorder?

Without thiamine PDH fails; a glucose load uses up the little thiamine left and can trigger Wernicke.

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

Sources: [PDHA1: Pyruvate dehydrogenase E1 component subunit alpha (human)](https://www.uniprot.org/uniprotkb/P08559/entry) (UniProt, 2026); [Pyruvate dehydrogenase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/pyruvate-dehydrogenase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [Pyruvate metabolism](https://reactome.org/PathwayBrowser/#/R-HSA-70268) (Reactome, 2026); [1NI4: Human pyruvate dehydrogenase](https://www.rcsb.org/structure/1NI4) (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/pyruvate-dehydrogenase-complex/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/pyruvate-dehydrogenase-complex/