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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
- Biochemical and biophysical research communications 2018 v.504 no.4 pp. 916-920
- calcium, exercise, inhibitory concentration 50, isoleucine, leucine, metabolism, mitochondria, oxidation, oxidoreductases, phosphorylation, protein kinases, skeletal muscle, thiamin, valine
- 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.