Zafra M F, Riquelme S, Castillo M, Garcia-Peregrin E
Department of Biochemistry, University of Granada, Spain.
Neurochem Res. 1987 Sep;12(9):787-90. doi: 10.1007/BF00971516.
The effect of clofibrate on the activity of the three mevalonate-activating enzymes has been studied for the first time in brain by reactions carried out using [2-14C] mevalonic acid as substrate and 105,000 g supernatants from 14-day-old chick brain. Mevalonate-5-pyrophosphate decarboxylase was clearly inhibited, while mevalonate kinase and mevalonate-5-phosphate kinase were not significantly affected. The effect of clofibrate on decarboxylase activity was progressive with increasing concentrations (1.25-5.00 mM) of the inhibitor. A transient inhibition and a subsequent activation as a function of clofibrate concentration seemed to occur for mevalonate kinase. Direct measurements of decarboxylase activity utilizing [2-14C] pyrophosphomevalonate as the specific substrate of this enzyme corroborated these results. Kinetic studies showed that clofibrate competes with the substrate ATP.
首次在大脑中通过使用[2-¹⁴C]甲羟戊酸作为底物以及14日龄鸡脑的105,000g上清液进行的反应，研究了氯贝丁酯对三种甲羟戊酸激活酶活性的影响。甲羟戊酸-5-焦磷酸脱羧酶明显受到抑制，而甲羟戊酸激酶和甲羟戊酸-5-磷酸激酶未受到显著影响。随着抑制剂浓度（1.25 - 5.00 mM）的增加，氯贝丁酯对脱羧酶活性的影响逐渐增强。甲羟戊酸激酶似乎随着氯贝丁酯浓度的变化出现短暂抑制和随后的激活。利用[2-¹⁴C]焦磷酸甲羟戊酸作为该酶的特异性底物直接测量脱羧酶活性证实了这些结果。动力学研究表明，氯贝丁酯与底物ATP竞争。
