Effects of liver failure on branched-chain α-keto acid dehydrogenase complex in rat liver and muscle: comparison between acute and chronic liver failure

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 (Fisherʹs 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.