三甲基苯基磷酸酯对神经毒性酯酶的抑制及其酶促动力学分析

以可使人和敏感动物产生迟发性神经毒性的有机磷化合物三甲基苯基磷酸酯（TOCP）为测试药物,研究其在体外对成年产卵来航母鸡不同神经组织神经毒性酯酶（NTE）活性抑制的敏感性及其抑制的动力学．结果表明,外周神经NTE对于TOCP的抑制比中枢神经NTE敏感得多．TOCP对鸡脑、脊髓和坐骨神经中NTE抑制的I50值．分别为：1．9323、2．3950和0．0035mmol／L．NTE酶促动力学研究显示,鸡脑NTE催化分解底物戊酸苯酯（PV）的Vmax为62．10nmol·min-1·mg-1,Km为0．92mmol／L．TOCP对鸡脑NTE的抑制属竞争性抑制类型,并有"底物抑制"现象．

Studies on Inhibition of Neuropathy Target Esterase by Tri-o-cresyl Phosphate and the Kinetics of NTE of Hens Brain in vitro

Studies on inhibition of neuropathy target esterase(NTE)from different nervous tissues of adult laying white Leghorn hens(Gallus gallus domesticus)by tri-o-cresyl phosphate(TOCP) in vitro has been carried out. The results show that sensitivity of NTE from peripheral nerves to inhibition of TOCP is much higher than that NTE from central nerves of hens, the I50 values of NTE from sciatic nerve, spinal cord, and brain of hens to inhibition of TOCP are 0. 0035 mmol/L,2. 3950 mmol/L, and 1. 9323 mmol/L respectively. And the second-order rate constants(Ka) calculated from the different TOCP concentrations are 174. 77(mol/L) - 1·min- 1, 50. 38(mol/L) -1.min - 1, and 107. 79(mol/L) - 1·min- 1, respectively, for the samples of sciatic merve, spinal cord, and brain. As phenyl valerate(PV) was ed as a substrate, the value of km of NTE from hens brain tested is 0. 92 mmol/L and the Vmax 62. 10 nmol (min·mg). The kinetic study of TOCP inhibiting NTE from hens brain shows that the inhibition of TOCP to NTE may be classified into the type of "competitive"and the so-called phenomenon of "substrate inhibition"was also Observe in the experiments. Ail the ahove results support the assume that NTE as a protein may perform physiological function as a receptor in the body.