Baudry M, Kessler M, Smith E K, Lynch G
Neurosci Lett. 1982 Jul 20;31(1):41-6. doi: 10.1016/0304-3940(82)90051-9.
The effects of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, on the phosphorylation of the alpha-subunit of pyruvate dehydrogenase and on the activity of pyruvate dehydrogenase (pyruvate:lipoamide oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1, PDH) were investigated in rat hippocampal slices. Incubating hippocampal slices with increasing concentrations of DCA resulted in an increase in the active portion of PDH, without changes in the total PDH activity, as well as an increase in the in vitro phosphorylation of alpha-PDH. The effect of DCA on PDH activity was very rapid, being almost maximal after 5 min. These results indicate that DCA in the hippocampal slice preparation inhibits PDH kinase and consequently stimulates PDH activity by decreasing its endogenous state of phosphorylation. Moreover the time-course of the effect of DCA suggests that the turnover rate of the phosphate group carried by alpha-PDH is very rapid and can be manipulated by altering PDH kinase activity.
在大鼠海马切片中，研究了丙酮酸脱氢酶激酶抑制剂二氯乙酸（DCA）对丙酮酸脱氢酶α亚基磷酸化以及丙酮酸脱氢酶（丙酮酸：硫辛酰胺氧化还原酶（脱羧和乙酰基受体化），EC 1.2.4.1，PDH）活性的影响。用浓度递增的DCA孵育海马切片，导致PDH活性部分增加，而总PDH活性无变化，同时α-PDH的体外磷酸化也增加。DCA对PDH活性的影响非常迅速，5分钟后几乎达到最大值。这些结果表明，在海马切片制备中，DCA抑制PDH激酶，从而通过降低其内源性磷酸化状态来刺激PDH活性。此外，DCA作用的时间进程表明，α-PDH携带的磷酸基团的周转率非常快，并且可以通过改变PDH激酶活性来调控。
