依赖钙的焦磷酸硫胺素对支链α-酮酸脱氢酶激酶的抑制作用。
Ca-dependent inhibition of branched-chain α-ketoacid dehydrogenase kinase by thiamine pyrophosphate.
机构信息
Laboratory of Nutritional Biochemistry, Department of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.
Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS, 66160, USA.
出版信息
Biochem Biophys Res Commun. 2018 Oct 12;504(4):916-920. doi: 10.1016/j.bbrc.2018.09.038. Epub 2018 Sep 15.
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 in the physiological range greatly increases the sensitivity of BDK to inhibition by TPP (IC of 2.5 μM in the presence of 1 μM free Ca). This novel mechanism may be responsible for the stimulation of BCAA oxidation by conditions that increase mitochondrial free Ca levels, e.g. in skeletal muscle during exercise.
支链氨基酸（BCAA：亮氨酸、异亮氨酸和缬氨酸）的分解代谢受支链α-酮酸脱氢酶（BCKDH）复合物的调节，而 BCKDH 激酶（BDK）催化的磷酸化又反过来调节 BCKDH 复合物。焦磷酸硫胺素（TPP）作为 BCKDH 复合物的 E1 成分的辅酶是必需的，它还可以通过抑制 BDK 来激活复合物。本研究表明，生理范围内的游离 Ca2+ 大大增加了 BDK 对 TPP 抑制的敏感性（在 1 μM 游离 Ca2+ 存在下，IC 为 2.5 μM）。这种新的机制可能是导致线粒体游离 Ca2+ 水平升高（例如运动时骨骼肌）时刺激 BCAA 氧化的原因。
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