Branched-chain amino acid catabolism in exercise and liver disease

Yoshiharu Shimomura, Takashi Honda, Makoto Shiraki, Taro Murakami, Juichi Sato, Hisamine Kobayashi, Kazunori Mawatari, Mariko Obayashi, Robert A. Harris

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63 Scopus citations


Branched-chain α-keto acid dehydrogenase (BCKDH) complex, the enzyme catalyst for the second step of the BCAA catabolic pathway, plays a central role in the regulation of BCAA catabolism. The activity of the complex is regulated by a covalent modification cycle in which phosphorylation by BCKDH kinase inactivates and dephosphorylation by BCKDH phosphatase activates the complex. Many studies suggest that control of the activity of the kinase is a primary determinant of the activity of the complex. The kinase exists at all times in the mitochondrial matrix space in two forms, with a large amount being free and a smaller amount bound rather tightly to the BCKDH complex. Only the bound form of the kinase appears to be catalytically active and, therefore, responsible for phosphorylation and inactivation of the complex. α-Ketoisocaproate, the transamination product of leucine and the most important known physiological inhibitor of BCKDH kinase, promotes release of the kinase from the complex. α-Chloroisocaproate, the analogue of leucine and the most potent known inhibitor of the kinase, is more effective than α-ketoisocaproate in promoting release of BCKDH kinase from the complex. Exercise and chronic liver disease (liver cirrhosis) likewise decrease the amount of the kinase bound to the complex in rat liver. The resulting activation of the BCKDH complex appears responsible for the increase in BCAA catabolism caused by exercise and liver cirrhosis. Our findings support the use of BCAA supplements for patients with liver cirrhosis.

Original languageEnglish (US)
Pages (from-to)250S-253S
JournalJournal of Nutrition
Issue number1
StatePublished - Jan 1 2006


  • α-chloroisocaproate
  • BCKDH complex
  • BCKDH kinase
  • Branched-chain amino acids
  • Exercise
  • Leucine, α-ketoisocaproate
  • Liver cirrhosis
  • TNFα

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

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    Shimomura, Y., Honda, T., Shiraki, M., Murakami, T., Sato, J., Kobayashi, H., Mawatari, K., Obayashi, M., & Harris, R. A. (2006). Branched-chain amino acid catabolism in exercise and liver disease. Journal of Nutrition, 136(1), 250S-253S.