Branched-Chain Amino Acids

D. T. Chuang

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations


Branched-chain amino acids (BCAAs) leucine, isoleucine, and valine in the muscle are converted into branched-chain α-ketoacids (BCKAs) through transamination. BCKAs circulated to the liver then undergo oxidative decarboxylation, mediated by the mitochondrial BCKA dehydrogenase complex (BCKDC), to produce branched-chain acyl-coenzymes. Genetic defects in the BCKDC result in maple syrup urine disease (MSUD), characterized by often-fatal ketoacidosis, neurological derangements, and mental retardation. The rate-limiting step in BCAA oxidation is at the BCKDC, which is acutely regulated by phosphorylation (inactivation)/dephosphorylation (reactivation), in response to hormonal and nutritional stimuli. Among BCAAs, leucine serves as key nutrition and endocrine signals to promote protein synthesis in muscle and trigger insulin release from pancreatic β-islet cells. A murine knockout model with block at the transamination step provokes a leucine-mediated energy-wasting futile cycle, resulting in significantly reduced body weight and body fat mass. Similar effects were obtained with dietary supplements of leucine or BCAAs. In the brain, a leucine-glutamate cycle is responsible for maintaining a steady supply of glutamate, a major excitatory neurotransmitter for interneuronal communication. BCKAs accumulated in MSUD compromise brain energy metabolism by blocking the respiratory chain and inhibiting creatine kinase activity. The above advances indicate that BCAAs and BCKAs are important amino acids that play a multifaceted role in metabolism, neurophysiology, and clinical applications.

Original languageEnglish (US)
Title of host publicationEncyclopedia of Biological Chemistry
Subtitle of host publicationSecond Edition
PublisherElsevier Inc.
Number of pages6
ISBN (Electronic)9780123786319
ISBN (Print)9780123786302
StatePublished - Feb 15 2013


  • BCATm knockout mice
  • Branched-chain amino acid metabolon
  • Branched-chain amino acid oxidation
  • Branched-chain amino acids
  • Branched-chain α-ketoacid dehydrogenase complex
  • Branched-chain α-ketoacid dehydrogenase kinase knockout mice
  • Branched-chain α-ketoacids
  • Energy-wasting futile cycle
  • Leucine
  • Leucine signaling
  • Leucine-glutamate cycle
  • Macromolecular organization
  • Maple syrup urine disease
  • PP2Cm phosphatase
  • Phosphorylation/dephosphorylation

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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