Effects of liver failure on branched-chain alpha-keto acid dehydrogenase complex in rat liver and muscle: comparison between acute and chronic liver failure.
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.
Honda
Takashi
T
Therapeutic Medicine, School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
Fukuda
Yoshihide
Y
Nakano
Isao
I
Katano
Yoshiaki
Y
Goto
Hidemi
H
Nagasaki
Masaru
M
Sato
Yuzo
Y
Murakami
Taro
T
Shimomura
Yoshiharu
Y
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
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