Biochemistry · Enzyme
Branched-chain α-keto acid dehydrogenase (BCKDH) !
BCKDH breaks down leucine, isoleucine and valine after their transamination. If it fails, urine smells like maple syrup.
Updated 2026-11-01
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Key facts
- It oxidatively decarboxylates the keto acids of leucine, isoleucine and valine to their acyl-CoAs.
- A complex built like PDH and α-KGDH: E1 (BCKDHA and BCKDHB), E2 (DBT) and E3 (DLD).
- It needs thiamine pyrophosphate, lipoate, CoA, FAD and NAD⁺.
- Branched-chain amino acids are transaminated mainly in muscle, not in the liver.
Structure
- 1X7Y: the human E1 component (α₂β₂ heterotetramer) with thiamine pyrophosphate.
Regulation
- A specific kinase (BCKDK) switches it off by phosphorylation; a phosphatase (PPM1K) switches it back on.
- Branched-chain keto acids inhibit that kinase and so activate the complex.
Inhibitors and toxins
- Arsenite (binds lipoate, as in PDH)
Clinical notes
- Maple syrup urine disease: leucine, which is neurotoxic, builds up.
- Some mild forms respond to thiamine.
- Plasma alloisoleucine is the diagnostic marker.
Pathways
Related conditions
Related
- Pyruvate dehydrogenase complex (PDH)
- α-Ketoglutarate dehydrogenase
- Glucogenic and ketogenic amino acids
- Transamination and deamination
Test yourself
Think of the answer, then tap the question to see it.
Which three amino acids does this complex break down?
Leucine, isoleucine and valine, after they are turned into their keto acids.
Which two other complexes share its design and cofactors?
Pyruvate dehydrogenase and α-ketoglutarate dehydrogenase: all three use TPP, lipoate, CoA, FAD and NAD⁺ and share E3.
Which plasma metabolite confirms deficiency of this complex?
Alloisoleucine, which only appears when branched-chain keto acids pile up.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: BCKDHA: 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (human) (UniProt, 2026); Maple syrup urine disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1X7Y: Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.