Poster Topical Area: Energy and Macronutrient Metabolism

Location: Hall D

Poster Board Number: 510

P10-111 - Calcium ion enhances inhibition of the BCKDH kinase by thiamine pyrophosphate

Monday, Jun 11
8:00 AM – 3:00 PM

The main catabolic pathways of branched-chain amino acids (BCAAs) are located in mitochondria. The first two steps of the pathway are common to the three BCAAs (leucine, isoleucine, and valine). The first step is transamination of the BCAAs to form branched-chain alpha-ketoacids (BCKAs), catalyzed by branched-chain aminotransferase (BCAT), and the second step is the oxidative decarboxylation of the BCKAs to produce corresponding CoA esters, catalyzed by the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. Since the latter is a committed step in the catabolism of BCAAs, the regulation of BCKDH complex is very important in the homeostasis of the free BCAA concentrations. The BCKDH complex is regulated by covalent modification, and BCKDH kinase (BDK) is responsible for inactivation of the complex by phosphorylation. Thiamine pyrophosphate (TPP) is known as the coenzyme of the complex as well as the BDK inhibitor. In the present study, we found that free calcium ion in the physiological range greatly increases the sensitivity of BDK to TPP: inhibition of the BDK by TPP with the IC50 of 14 µM and 0.11 µM in the absence and presence of 1 µM free calcium ion, respectively. These findings suggest a novel mechanism for the calcium ion-dependent regulation of BCKDH complex.




Funding Source: This work was in part supported by JSPS KAKENHI (No. 17H03817 from Grant-in-Aid for Scientific Research (B) (to YS).

CoAuthors: Seisuke Noguchi – Nagoya University Graduate School of Bioagricultural Sciences; Yasuyuki Kitaura – Nagoya University Graduate School of Bioagricultural Sciences

Yoshiharu Shimomura

Professor
Nagoya University Graduate School of Bioagricultural Sciences
Nagoya, Aichi, Japan