氟化物在体外对胆碱酯酶的抑制作用。

Inhibition of cholinesterases by fluoride in vitro.

Cimasoni G

Biochem J. 1966 Apr;99(1):133-7. doi: 10.1042/bj0990133.

Abstract

Series of colorimetric dynamic assays allowed the study of the inhibition of cholinesterases by F(-) ions in vitro, by using, as sources of enzyme, whole human blood, human serum, homogenized rat brain and two preparations of red blood cells (human and bovine) whose enzymic purity was ascertained. 2. The first evidence of inhibition of human serum pseudocholinesterase by fluoride was noticed at 15-25mum-fluoride. Ten times as much fluoride was needed to start inhibition of acetylcholinesterase of the red blood cells. 3. The action of fluoride on the enzymic reaction was immediate. The reversibility of the inhibition was shown by dialysis and dilution. 4. Kinetic measurements showed that the inhibition under study was not dependent on the substrate concentration and was of the uncompetitive type, similar to that observed in the presence of a heavy metal (cadmium). 5. The activity of serum cholinesterase did not change in the absence of Mg(2+) and Ca(2+) ions. Fluoride was shown to inhibit the enzyme in the absence of these ions as well as of phosphate. 6. Fluoride could inhibit cholinesterases in the presence of three different substrates and had no action on the non-enzymic hydrolysis. 7. It is thought that the halide is bound reversibly to the enzyme molecule, with the probable exclusion of the active site, but no firm conclusion could be reached on this point.

摘要

一系列比色动力学分析使得能够在体外研究氟离子对胆碱酯酶的抑制作用，所使用的酶源包括全血、人血清、大鼠脑匀浆以及两种红细胞制剂（人源和牛源），且已确定了这些酶源的纯度。2. 在氟离子浓度为15 - 25μmol时首次发现氟对人血清假性胆碱酯酶有抑制作用。红细胞乙酰胆碱酯酶开始受到抑制所需的氟离子量是前者的10倍。3. 氟对酶促反应的作用是即时的。通过透析和稀释证明了这种抑制作用是可逆的。4. 动力学测量表明，所研究的抑制作用不依赖于底物浓度，属于非竞争性类型，类似于在重金属（镉）存在时观察到的情况。5. 在没有镁离子和钙离子的情况下，血清胆碱酯酶的活性没有变化。已表明氟在没有这些离子以及磷酸盐的情况下也能抑制该酶。6. 氟在存在三种不同底物的情况下都能抑制胆碱酯酶，并且对非酶促水解没有作用。7. 据认为，卤化物与酶分子可逆结合，可能排除了活性位点，但在这一点上无法得出确凿结论。