Regulation of branched-chain α-keto acid dehydrogenase kinase expression in rat liver
Regulation of branched-chain α-keto acid dehydrogenase kinase expression in rat liver
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DOI：
10.1093/jn/131.3.841s
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发表时间：
2001-03-01
影响因子：
4.2
通讯作者：
Shimomura, Y
中科院分区：
文献类型：
--
作者：
Harris, RA;Kobayashi, R;Shimomura, Y
支链氨基酸是有毒的过量，但必须保存蛋白质合成。这在很大程度上是通过磷酸化/去磷酸化控制支链α-酮酸脱氢酶复合物的活性来实现的。至少在大鼠中，肝酶活性的调节显得特别重要，因为该组织中复合物的异常高活性使肝脏成为其他组织释放的过量支链α-酮酸的主要清除所。支链α-酮酸脱氢酶复合物通过磷酸化失活的程度由支链α-酮酸脱氢酶激酶的活性决定，该激酶本身受到变构效应物以及影响其表达水平的因素的调节。在这些因素中，已经确定的是由亮氨酸转氨基作用产生的α-酮酸，其是激酶的有效抑制剂，以及对膳食蛋白质的饥饿，其导致支链α-酮酸脱氢酶激酶的表达增加。后一个发现导致了营养素和激素调节支链α-酮酸脱氢酶激酶表达的工作假设。已经获得了甲状腺激素、糖皮质激素和过氧化物酶体增殖物激活受体α配体参与的证据，甲状腺激素诱导激酶表达，而糖皮质激素和过氧化物酶体增殖物激活受体α配体抑制激酶表达。在缺乏蛋白质的动物中，甲状腺激素的血液水平增加被认为是支链α-酮酸脱氢酶激酶表达增加的原因。
Branched-chain amino acids are toxic in excess but have to be conserved for protein synthesis. This is accomplished in large part by control of the activity of the branched-chain alpha -keto acid dehydrogenase complex by phosphorylation/dephosphorylation. Regulation of the activity of the hepatic enzyme appears particularly important, at least in rats, since an exceptional high activity of the complex in this tissue makes the liver the primary clearing house for excess branched-chain alpha -keto acids released by other tissues. The degree to which the branched-chain alpha -keto acid dehydrogenase complex is inactivated by phosphorylation is determined by the activity of the branched-chain alpha -keto acid dehydrogenase kinase, which is itself regulated by allosteric effectors as well as factors that affect its level of expression. Well established among these are the alpha -keto acid produced by leucine transamination, which is a potent inhibitor of the kinase, and starvation for dietary protein, which causes increased expression of the branched-chain alpha -keto acid dehydrogenase kinase. The latter finding resulted in the working hypothesis that nutrients and hormones regulate expression of the branched-chain alpha -keto acid dehydrogenase kinase. Evidence has been obtained for the involvement of thyroid hormone, glucocorticoids and ligands for peroxisome proliferator-activated receptor alpha, Thyroid hormone induces, whereas glucocorticoids and peroxisome proliferator-activated receptor alpha ligands repress, expression of the kinase. Increased blood levels of thyroid hormone are proposed to be responsible for increased expression of branched-chain alpha -keto acid dehydrogenase kinase in animals starved for protein.