Gender difference in regulation of branched-chain amino acid catabolism
Gender difference in regulation of branched-chain amino acid catabolism
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DOI：
10.1042/bj3270449
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发表时间：
1997-10-15
影响因子：
4.1
通讯作者：
Harris, RA
中科院分区：
文献类型：
--
作者：
Kobayashi, R;Shimomura, Y;Harris, RA
雄性和雌性大鼠在明暗循环期间对肝支链 2-含氧酸脱氢酶 (BCODH) 复合物活性状态的调节存在显着差异。雌性大鼠在复合体的活动状态中表现出深刻的昼夜节律，而在雄性大鼠中未观察到。无论性别如何，大多数复合物在黑暗期中期和光照期早期被去磷酸化并活跃，并且这种形式的复合物在光照期末期的雄性大鼠中占主导地位。相比之下，雌性大鼠中的大部分复合物在光照期结束时变得磷酸化和失活。性腺切除术阻止了女性的昼夜节律，但对男性没有影响，这表明 BCODH 复合物调节中的这种性别差异需要女性性激素。支链 2-含氧酸（BCODH 激酶的已知调节因子）水平的变化似乎与此无关。相反，早上和晚上之间发生的 BCODH 激酶活性增加是导致雌性大鼠 BCODH 复合物失活的原因。激酶活性的增加是由于与 BCODH 复合物相关的激酶蛋白量的增加。因此，BCODH 激酶的量及其活性的显着昼夜变化导致雌性大鼠肝脏 BCODH 复合物的活性状态大幅波动。这项研究为支链氨基酸分解代谢调节中的性别特异性差异提供了第一个证据。
Regulation of the activity state of the hepatic branched-chain 2-oxo acid dehydrogenase (BCODH) complex during the light-dark cycle differs markedly in male and female rats. Female rats exhibit a profound diurnal rhythm in the activity state of the complex that is not observed in male rats. Regardless of gender, most of the complex was dephosphorylated and active in the middle of the dark period and early in the light period, and this form of the complex predominated in male rats at the end of the light period. In contrast, most of the complex in female rats became phosphorylated and inactive by the end of the light period. Gonadectomy prevented the diurnal rhythm in females but was without effect in males, indicating that female sex hormones are required for this gender difference in regulation of the BCODH complex. Changes in levels of branched-chain 2-oxo acids, known regulators of BCODH kinase, do not seem to be involved; rather, an increase in BCODH kinase activity occurring between morning and evening is responsible for inactivation of the BCODH complex in female rats. The increase in kinase activity is due to an increase in the amount of kinase protein associated with the BCODH complex. Thus a marked diurnal variation in the amount of BCODH kinase and therefore its activity results in large swings in the activity state of the liver BCODH complex in female rats. This study provides the first evidence for a gender-specific difference in the regulation of branched-chain amino acid catabolism.