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

Journal Article · Mon Oct 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.09.038· OSTI ID:23134164

Noguchi, Seisuke; Kondo, Yusuke; Ito, Rina; Katayama, Takahiro; Kazama, Shunsuke; Kadota, Yoshihiro; Kitaura, Yasuyuki ^[1]; Harris, Robert A. ^[2]; Shimomura, Yoshiharu ^[1]

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1. Laboratory of Nutritional Biochemistry, Department of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601 (Japan)
2. Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS, 66160 (United States)

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{sup 2+} in the physiological range greatly increases the sensitivity of BDK to inhibition by TPP (IC{sub 50} of 2.5 μM in the presence of 1 μM free Ca{sup 2+}). This novel mechanism may be responsible for the stimulation of BCAA oxidation by conditions that increase mitochondrial free Ca{sup 2+} levels, e.g. in skeletal muscle during exercise.

• OSTI ID: 23134164
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 504; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CATABOLISM
LEUCINE
MITOCHONDRIA
OXIDOREDUCTASES
PHOSPHOTRANSFERASES
PYROPHOSPHATES
THIAMINE
VALINE