Sok D E, Kim M R
Department of Food and Nutrition, Chungnam National University, Taejeon, Korea.
Neurochem Res. 1995 Feb;20(2):151-7. doi: 10.1007/BF00970539.
Inhibition of a Zn(2+)-glycerophosphocholine cholinephosphodiesterase by thiols or tellurites were examined mechanistically. Inactivation of the phosphodiesterase by thio-carboxylates, which was due to the removal of Zn2+ in the catalytic site, was enhanced by introduction of an amino group in the structure of thiols, suggesting the presence of an anionic site adjacent to a Zn2+ site. In support of the suggestion, it was found that thiols, associable with both a Zn2+ site and an anionic site, were more potent reversible inhibitors; dimethylaminoethanethiol (Ki, 17 microM), diethylaminoethanethiol (Ki, 1.2 microM) and thiocholine (Ki, 2.6 microM). Meanwhile, the inhibition of the phosphodiesterase by tellurites is ascribed to the binding of tellurite anions to a Zn2+ site, based on the protective action of tellurite anions against the inactivation of the enzyme by EDTA. Moreover, the inhibition of the phosphodiesterase by tellurites was prevented by phosphate ions, which expressed the protective effect against EDTA inactivation. In further support, it was observed that tellurite and thiocholine appeared to interact with active site in an additive manner, in contrast to a synergistic action between tellurites and quaternary ammonium compounds such as acetylcholine or choline.
对硫醇或亚碲酸盐对锌（2+）-甘油磷酸胆碱胆碱磷酸二酯酶的抑制作用进行了机理研究。硫代羧酸盐使磷酸二酯酶失活，这是由于催化位点上的锌离子被去除，而在硫醇结构中引入氨基会增强这种失活作用，这表明在锌离子位点附近存在一个阴离子位点。为支持这一观点，发现能够与锌离子位点和阴离子位点结合的硫醇是更有效的可逆抑制剂；二甲基氨基乙硫醇（Ki，17 microM）、二乙氨基乙硫醇（Ki，1.2 microM）和硫代胆碱（Ki，2.6 microM）。同时，基于亚碲酸根阴离子对该酶被EDTA失活的保护作用，亚碲酸盐对磷酸二酯酶的抑制作用归因于亚碲酸根阴离子与锌离子位点的结合。此外，磷酸根离子可防止亚碲酸盐对磷酸二酯酶的抑制作用，磷酸根离子对EDTA失活表现出保护作用。进一步的支持证据是，观察到亚碲酸盐和硫代胆碱似乎以加和方式与活性位点相互作用，这与亚碲酸盐和季铵化合物如乙酰胆碱或胆碱之间的协同作用形成对比。
