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

• Noguchi, Seisuke

• Kondo, Yusuke

• Ito, Rina

• Katayama, Takahiro

• Kazama, Shunsuke

• Kadota, Yoshihiro

• Kitaura, Yasuyuki

• Harris, Robert A.

• Shimomura, Yoshiharu

Abstract

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 Ca^2+ 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 Ca^2+). This novel mechanism may be responsible for the stimulation of BCAA oxidation by conditions that increase mitochondrial free Ca^2+ levels, e.g. in skeletal muscle during exercise.

Journal

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 504 (4), 916-920, 2018-10-12

  Elsevier社

Keywords

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

Details

• CRID: 1050282813790561792
• NII Article ID: 120006554494
• DOI: 10.1016/j.bbrc.2018.09.038
• HANDLE: 2237/00029271
• ISSN: 0006291X
• Web Site: https://nagoya.repo.nii.ac.jp/records/27071
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X18319569?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X18319569?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN