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Effects of liver failure on the enzymes in the branched-chain amino acid catabolic pathway.

Abstract
Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex catalyzes the committed step of the catabolism of branched-chain amino acids (BCAA). The liver cirrhosis chemically induced in rats raised the activity of hepatic BCKDH complex and decreased plasma BCAA and branched-chain alpha-keto acid concentrations, suggesting that the BCAA requirement is increased in liver cirrhosis. Since the effects of liver cirrhosis on the BCKDH complex in human liver are different from those in rat liver, further studies are needed to clarify the differences between rats and humans. In the valine catabolic pathway, crotonase and beta-hydroxyisobutyryl-CoA hydrolase are very important to regulate the toxic concentration of mitochondrial methacrylyl-CoA, which occurs in the middle part of valine pathway and highly reacts with free thiol compounds. Both enzyme activities in human and rat livers are very high compared to that of BCKDH complex. It has been found that both enzyme activities in human livers were significantly reduced by liver cirrhosis and hepatocellular carcinoma, suggesting a decrease in the capability to dispose methacrylyl-CoA. The findings described here suggest that alterations in hepatic enzyme activities in the BCAA catabolism are associated with liver failure.
AuthorsYoshiharu Shimomura, Takashi Honda, Hidemi Goto, Toshiaki Nonami, Tsuyoshi Kurokawa, Masaru Nagasaki, Taro Murakami
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 313 Issue 2 Pg. 381-5 (Jan 9 2004) ISSN: 0006-291X [Print] United States
PMID14684172 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Amino Acids, Branched-Chain
  • Multienzyme Complexes
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
  • Transaminases
  • branched-chain-amino-acid transaminase
  • Thiolester Hydrolases
  • 3-hydroxyisobutyryl-CoA hydrolase
  • Enoyl-CoA Hydratase
Topics
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) (metabolism)
  • Amino Acids, Branched-Chain (metabolism)
  • Animals
  • Enoyl-CoA Hydratase (metabolism)
  • Humans
  • Liver Failure (enzymology)
  • Multienzyme Complexes (metabolism)
  • Thiolester Hydrolases (metabolism)
  • Transaminases (metabolism)

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