TY - JOUR
T1 - Effects of liver failure on branched-chain α-keto acid dehydrogenase complex in rat liver and muscle
T2 - Comparison between acute and chronic liver failure
AU - Honda, Takashi
AU - Fukuda, Yoshihide
AU - Nakano, Isao
AU - Katano, Yoshiaki
AU - Goto, Hidemi
AU - Nagasaki, Masaru
AU - Sato, Yuzo
AU - Murakami, Taro
AU - Shimomura, Yoshiharu
N1 - Funding Information:
This work was supported in part by a grant-in-aid for scientific research (14370022 to Y.S.) from the Ministry of Education, Science, Sports and Culture, Japan.
PY - 2004/3
Y1 - 2004/3
N2 - Background/Aims: Branched-chain α-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 α-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.
AB - Background/Aims: Branched-chain α-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 α-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.
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U2 - 10.1016/j.jhep.2003.11.003
DO - 10.1016/j.jhep.2003.11.003
M3 - Article
C2 - 15123358
AN - SCOPUS:1242292350
SN - 0168-8278
VL - 40
SP - 439
EP - 445
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 3
ER -