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.
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
Related conditions
- Pyruvate dehydrogenase deficiency
- Wernicke encephalopathy (thiamine deficiency)
- Arsenic poisoning
- Lactic acidosis
Related
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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: PDHA1: Pyruvate dehydrogenase E1 component subunit alpha (human) (UniProt, 2026); Pyruvate dehydrogenase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Pyruvate metabolism (Reactome, 2026); 1NI4: Human pyruvate dehydrogenase (RCSB Protein Data Bank, 2026).
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