Ca2+-dependent inhibition of branched-chain α-ketoacid dehydrogenase kinase by thiamine pyrophosphate

Seisuke Noguchi, Yusuke Kondo, Rina Ito, Takahiro Katayama, Shunsuke Kazama, Yoshihiro Kadota, Yasuyuki Kitaura, Robert A. Harris, Yoshiharu Shimomura

Research output: Contribution to journalArticle

1 Scopus citations


Catabolism of the branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) is regulated by the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which in turn is regulated by phosphorylation catalyzed by BCKDH kinase (BDK). Thiamine pyrophosphate (TPP) is required as a coenzyme for the E1 component of the BCKDH complex and can also bring about activation of the complex by inhibiting BDK. The present study shows that free Ca2+ in the physiological range greatly increases the sensitivity of BDK to inhibition by TPP (IC50 of 2.5 μM in the presence of 1 μM free Ca2+). This novel mechanism may be responsible for the stimulation of BCAA oxidation by conditions that increase mitochondrial free Ca2+ levels, e.g. in skeletal muscle during exercise.

Original languageEnglish (US)
Pages (from-to)916-920
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Oct 12 2018
Externally publishedYes


  • Branched-chain amino acids
  • Branched-chain α-ketoacid dehydrogenase complex
  • Branched-chain α-ketoacid dehydrogenase kinase
  • Calcium ion
  • Thiamine pyrophosphate

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Ca<sup>2+</sup>-dependent inhibition of branched-chain α-ketoacid dehydrogenase kinase by thiamine pyrophosphate'. Together they form a unique fingerprint.

  • Cite this