Experimental hyperthyroidism causes inactivation of the branched-chain α-ketoacid dehydrogenase complex in rat liver
Experimental hyperthyroidism causes inactivation of the branched-chain α-ketoacid dehydrogenase complex in rat liver
复制标题
DOI：
10.1006/abbi.1999.1635
复制
发表时间：
2000-03-01
影响因子：
3.9
通讯作者：
Harris, RA
中科院分区：
文献类型：
--
作者：
Kobayashi, R;Shimomura, Y;Harris, RA
用每天 0.1 或 1 毫克/千克体重的甲状腺激素（T-3；3,5,3'-三碘甲状腺原氨酸）治疗大鼠 3 天诱发甲状腺功能亢进，导致肝支链 α-酮酸脱氢酶 (BCKDH) 的活性状态降低（处于活性、去磷酸化状态的酶的百分比） 复杂的。 24小时后，用0.1mg T-3/kg体重进行一次处理对BCKDH复合物的活性状态产生显着影响，表明活性状态的降低是由第一次施用T-3引发的。甲状腺功能亢进还导致 BCKDH 激酶活性稳定增加，BCKDH 激酶活性负责 BCKDH 复合物的磷酸化和失活，表明 T-3 通过诱导其激酶导致 BCKDH 复合物失活，Western blot 分析还显示，甲状腺功能亢进时 BCKDH 激酶蛋白的量增加，血浆中 T-3 的血浆水平没有变化。 在 T-3 处理的大鼠中观察到支链 α-酮酸，反对这些已知的 BCKDH 激酶活性调节因子的参与。由于其激酶过度表达而导致肝脏 BCKDH 复合物失活，可能会在甲状腺功能亢进期间保存蛋白质合成所必需的支链氨基酸 (C) 2000 学术出版社。
Hyperthyroidism induced by 3-day treatment of rats with thyroid hormone (T-3; 3,5,3'-triiodothyronine) at 0.1 or 1 mg/kg body wt/day resulted in a reduced activity state (% of enzyme in its active, dephosphorylated state) of the hepatic branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. One treatment with 0.1 mg T-3/kg body wt caused a significant effect on the activity state of BCKDH complex after 24 h, indicating that the reduction of the activity state was triggered by the first administration of T-3. Hyperthyroidism also caused a stable increase in BCKDH kinase activity, the enzyme responsible for phosphorylation and inactivation of the BCKDH complex, suggesting that T-3 caused inactivation of the BCKDH complex by induction of its kinase, Western blot analysis also revealed increased amounts of BCKDH kinase protein in response to hyperthyroidism, No change in the plasma levels of branched-chain alpha-keto acids was observed in T-3-treated rats, arguing against an involvement of these known regulators of BCKDH kinase activity, Inactivation of the hepatic BCKDH complex as a consequence of overexpression of its kinase may save the essential branched-chain amino acids for protein synthesis during hyperthyroidism (C) 2000 Academic Press.