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Branched-Chain Amino Acid Catabolism in Exercise and Liver Disease
- Source :
- The Journal of Nutrition. 136:250S-253S
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- Branched-chain alpha-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. alpha-Ketoisocaproate, the transamination product of leucine and the most important known physiological inhibitor of BCKDH kinase, promotes release of the kinase from the complex. alpha-Chloroisocaproate, the analogue of leucine and the most potent known inhibitor of the kinase, is more effective than alpha-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.
- Subjects :
- Nutrition and Dietetics
Catabolism
Kinase
Liver Diseases
Branched-chain amino acid
Medicine (miscellaneous)
Biology
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Rats
Enzyme Activation
Dephosphorylation
chemistry.chemical_compound
Enzyme activator
Liver
chemistry
Biochemistry
Mitochondrial matrix
Animals
Humans
Phosphorylation
Leucine
Exercise
Amino Acids, Branched-Chain
Subjects
Details
- ISSN :
- 00223166
- Volume :
- 136
- Database :
- OpenAIRE
- Journal :
- The Journal of Nutrition
- Accession number :
- edsair.doi.dedup.....0d359ef3d2b1f8d9db015281626b23a5