title: Effects of liver failure on branched-chain alpha-keto acid dehydrogenase complex in rat liver and muscle: comparison between acute and chronic liver failure.
abstract: OBJECTIVE
  Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex catalyses the committed step in the branched-chain amino acid (BCAA) catabolic pathway. In many cases of liver failure, the serum BCAAs/aromatic amino acids ratio (Fisher's ratio) decreases, and BCAAs have been administered to patients with liver failure to correct this ratio. We conducted an animal study to examine whether the effects on hepatic BCKDH complex differ between acute liver failure (ALF) and chronic liver failure (CLF).
  
  
  METHODS
  ALF and CLF was induced in rats by a single high-dose injection and 21 weeks of repeated low-dose injections of carbon tetrachloride, respectively. Plasma BCAA and branched-chain alpha-keto acid (BCKA) levels, and activities and protein amounts of hepatic BCKDH complex and kinase were measured.
  
  
  RESULTS
  ALF was characterized by elevated plasma BCAA and BCKA levels and decreased hepatic BCKDH activity. CLF was characterized by decreased plasma BCAA and BCKA levels and increased hepatic BCKDH activity. This increase in BCKDH activity in CLF was associated with the decreased BCKDH kinase, which is responsible for the BCKDH inactivation.
  
  
  CONCLUSIONS
  The results obtained in the present study suggest that BCAA catabolism is suppressed in ALF and increased in CLF.
authors.affiliation: Therapeutic Medicine, School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Isao
authors.initials: I
authors.lastname: Nakano
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katano
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.forename: Masaru
authors.initials: M
authors.lastname: Nagasaki
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Sato
authors.forename: Taro
authors.initials: T
authors.lastname: Murakami
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Shimomura
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D002908:Chronic Disease; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007527:Isoenzymes / Q000235:genetics; D007651:Keto Acids / Q000097:blood; D008099:Liver / Q000201:enzymology*; D017093:Liver Failure / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D011494:Protein Kinases / Q000097:blood / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000597:Amino Acids, Branched-Chain; D007527:Isoenzymes; D007651:Keto Acids; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D002950:Citrate (si)-Synthase; D011494:Protein Kinases; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase