Branched-chain 2-oxo acid dehydrogenase complex activation by tetanic contractions in rat skeletal muscle.
Branched-chain 2-oxo acid dehydrogenase complex activation by tetanic contractions in rat skeletal muscle.
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DOI：
10.1016/0304-4165(93)90112-l
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发表时间：
1993-06
期刊：
影响因子：
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通讯作者：
Y. Shimomura;H. Fujii;M. Suzuki;N. Fujitsuka;M. Naoi;S. Sugiyama;R. Harris
中科院分区：
文献类型：
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作者：
Y. Shimomura;H. Fujii;M. Suzuki;N. Fujitsuka;M. Naoi;S. Sugiyama;R. Harris
大鼠骨骼肌中的支链2-含氧酸脱氢酶复合物被电刺激引起的肌肉收缩激活。这种激活归因于磷酸化酶复合物的去磷酸化，并且总酶活性不被肌肉收缩改变。酶复合物的激活发生在电刺激腿的肌肉中，但不发生在非刺激（对照）腿的肌肉中，表明血液成分不参与肌肉中酶激活的机制。腺嘌呤核苷酸，支链氨基和2-含氧酸和乳酸在肌肉中被确定为可能的因素，通过抑制支链2-含氧酸脱氢酶激酶活性调节酶复合物的活性。由肌肉收缩引起的酶激活的配置文件是不同的腺嘌呤核苷酸浓度的变化，但类似于肌肉中的支链氨基和2-含氧酸的浓度的变化。在收缩期间，受刺激肌肉中的乳酸盐浓度升高3-5倍，表明细胞内酸化。以前的研究表明，从亮氨酸衍生的2-含氧酸是一种有效的激酶抑制剂。这些结果表明，由于肌肉收缩增加的细胞内支链2-含氧酸由于运动诱导的肌细胞酸化而积累在线粒体中，导致通过抑制激酶而激活支链2-含氧酸脱氢酶复合物。
Branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle was activated by muscle contractions elicited by electrical stimulation. This activation was attributed to dephosphorylation of the phosphorylated enzyme complex, and the total enzyme activity was not altered by muscle contractions. The activation of the enzyme complex occurred in the muscle of the electrically stimulated leg, but not in the muscle of the non-stimulated (control) leg, indicating that blood components are not involved in the mechanism of the enzyme activation in the muscle. Adenine nucleotides, branched-chain amino and 2-oxo acids and lactate in the muscle were determined as possible factors modulating the enzyme complex activity through inhibition of branched-chain 2-oxo acid dehydrogenase kinase activity. The profile of enzyme activation induced by muscle contractions was different from the alteration of the adenine nucleotide concentrations but was similar to the alteration of the concentrations of branched-chain amino and 2-oxo acids in the muscle. The lactate concentration in the stimulated muscle was elevated 3–5 fold during the contractions, indicating intracellular acidification. Previous studies have shown that the 2-oxo acid derived from leucine is a potent inhibitor of the kinase. These results suggest that intracellular branched-chain 2-oxo acids increased by muscle contractions accumulate in the mitochondria due to exercise-induced acidification of the muscle cell, resulting in activation of branched-chain 2-oxo acid dehydrogenase complex by inhibition of the kinase.