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 Harris

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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
JournalJournal of Nutrition
Volume136
Issue number1
StatePublished - Jan 2006

Fingerprint

3-methyl-2-oxobutanoate dehydrogenase (lipoamide)
Branched Chain Amino Acids
branched chain amino acids
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
amino acid metabolism
liver diseases
Liver Diseases
phosphotransferases (kinases)
exercise
Phosphotransferases
Exercise
liver cirrhosis
Liver Cirrhosis
Leucine
leucine
phosphorylation
Phosphorylation
transamination
metabolism
dephosphorylation

Keywords

  • 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

Cite this

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

Branched-chain amino acid catabolism in exercise and liver disease. / Shimomura, Yoshiharu; Honda, Takashi; Shiraki, Makoto; Murakami, Taro; Sato, Juichi; Kobayashi, Hisamine; Mawatari, Kazunori; Obayashi, Mariko; Harris, Robert.

In: Journal of Nutrition, Vol. 136, No. 1, 01.2006.

Research output: Contribution to journalArticle

Shimomura, Y, Honda, T, Shiraki, M, Murakami, T, Sato, J, Kobayashi, H, Mawatari, K, Obayashi, M & Harris, R 2006, 'Branched-chain amino acid catabolism in exercise and liver disease', Journal of Nutrition, vol. 136, no. 1.
Shimomura Y, Honda T, Shiraki M, Murakami T, Sato J, Kobayashi H et al. Branched-chain amino acid catabolism in exercise and liver disease. Journal of Nutrition. 2006 Jan;136(1).
Shimomura, Yoshiharu ; Honda, Takashi ; Shiraki, Makoto ; Murakami, Taro ; Sato, Juichi ; Kobayashi, Hisamine ; Mawatari, Kazunori ; Obayashi, Mariko ; Harris, Robert. / Branched-chain amino acid catabolism in exercise and liver disease. In: Journal of Nutrition. 2006 ; Vol. 136, No. 1.
@article{8a8600bbf6bc439ab7c4439ff3386e48,
title = "Branched-chain amino acid catabolism in exercise and liver disease",
abstract = "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.",
keywords = "α-chloroisocaproate, BCKDH complex, BCKDH kinase, Branched-chain amino acids, Exercise, Leucine, α-ketoisocaproate, Liver cirrhosis, TNFα",
author = "Yoshiharu Shimomura and Takashi Honda and Makoto Shiraki and Taro Murakami and Juichi Sato and Hisamine Kobayashi and Kazunori Mawatari and Mariko Obayashi and Robert Harris",
year = "2006",
month = "1",
language = "English",
volume = "136",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "1",

}

TY - JOUR

T1 - Branched-chain amino acid catabolism in exercise and liver disease

AU - Shimomura, Yoshiharu

AU - Honda, Takashi

AU - Shiraki, Makoto

AU - Murakami, Taro

AU - Sato, Juichi

AU - Kobayashi, Hisamine

AU - Mawatari, Kazunori

AU - Obayashi, Mariko

AU - Harris, Robert

PY - 2006/1

Y1 - 2006/1

N2 - 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.

AB - 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.

KW - α-chloroisocaproate

KW - BCKDH complex

KW - BCKDH kinase

KW - Branched-chain amino acids

KW - Exercise

KW - Leucine, α-ketoisocaproate

KW - Liver cirrhosis

KW - TNFα

UR - http://www.scopus.com/inward/record.url?scp=31544461753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31544461753&partnerID=8YFLogxK

M3 - Article

VL - 136

JO - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

IS - 1

ER -