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

被引：10

作者：

Noguchi, Seisuke ^{[1
]}

Kondo, Yusuke ^{[1
]}

Ito, Rina ^{[1
]}

Katayama, Takahiro ^{[1
]}

Kazama, Shunsuke ^{[1
]}

Kadota, Yoshihiro ^{[1
]}

Kitaura, Yasuyuki ^{[1
]}

Harris, Robert A. ^{[2
]}

Shimomura, Yoshiharu ^{[1
]}

机构：

[1] Nagoya Univ, Grad Sch Bioagr Sci, Dept Appl Biosci, Lab Nutr Biochem, Nagoya, Aichi 4648601, Japan

[2] Univ Kansas, Dept Biochem & Mol Biol, Med Ctr, Kansas City, KS 66160 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2018年 / 504卷 / 04期

关键词：

Branched-chain amino acids; Branched-chain alpha-ketoacid dehydrogenase complex; Branched-chain alpha-ketoacid dehydrogenase kinase; Thiamine pyrophosphate; Calcium ion; AMINO-ACID CATABOLISM; SKELETAL-MUSCLE; RAT-LIVER; EXERCISE; PYRUVATE; PROTEIN; METABOLISM; COMPLEX; ACTIVATION; MECHANISM;

D O I：

10.1016/j.bbrc.2018.09.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Catabolism of the branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) is regulated by the branched-chain alpha-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 mu M in the presence of 1 mu M 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. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：916 / 920

页数：5

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