Experimental hyperthyroidism causes inactivation of the branched-chain α-ketoacid dehydrogenase complex in rat liver

Rumi Kobayashi, Yoshiharu Shimomura, Megumi Otsuka, Kirill M. Popov, Robert A. Harris

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Hyperthyroidism induced by 3-day treatment of rats with thyroid hormone (T3; 3,5,3'-triiodothyronine) at 0.1 or 1 mg/kg body wt/day resulted in a reduced activity state (% of enzyme in its active, dephosphorylated state) of the hepatic branched-chain α-ketoacid dehydrogenase (BCKDH) complex. One treatment with 0.1 mg T3/kg body wt caused a significant effect on the activity state of BCKDH complex after 24 h, indicating that the reduction of the activity state was triggered by the first administration of T3. Hyperthyroidism also caused a stable increase in BCKDH kinase activity, the enzyme responsible for phosphorylation and inactivation of the BCKDH complex, suggesting that T3 caused inactivation of the BCKDH complex by induction of its kinase. Western blot analysis also revealed increased amounts of BCKDH kinase protein in response to hyperthyroidism. No change in the plasma levels of branched-chain α-keto acids was observed in T3-treated rats, arguing against an involvement of these known regulators of BCKDH kinase activity. Inactivation of the hepatic BCKDH complex as a consequence of overexpression of its kinase may save the essential branched-chain amino acids for protein synthesis during hyperthyroidism. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume375
Issue number1
DOIs
StatePublished - Mar 1 2000

Keywords

  • Branched-chain α-ketoacid dehydrogenase
  • Branched-chain α-ketoacid dehydrogenase kinase
  • Branched-chain amino acids
  • Liver
  • Muscle
  • Rat
  • Thyroid

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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