Klegeris A, Korkina L G, Greenfield S A
University Department of Pharmacology, Oxford, UK.
Free Radic Biol Med. 1995 Feb;18(2):223-30. doi: 10.1016/0891-5849(94)00115-z.
Acetylcholinesterase has an action in the central nervous system, independent of hydrolysis of acetylcholine. This study explored the possible interaction between the two molecules: the effects of acetylcholinesterase on the autoxidation of the catecholamine were tested, and, in turn, modification of the catalytic activity of the enzyme by products of dopamine oxidation were studied. Acetylcholinesterase selectively inhibited the speed of quinone production from dopamine as well as accumulation of hydrogen peroxide, whilst the rate of generation of superoxide was increased. Analysis of absorption spectra revealed the formation of a new product, which appeared after mixing acetylcholinesterase and dopamine in neutral pH. In all cases, butyrylcholinesterase was ineffective. Incubation of acetylcholinesterase in the presence of dopamine resulted in a significant decrease in the catalytic activity of the enzyme. The effects of application of preparations modifying autoxidation of dopamine (SOD, catalase, peroxidase) suggested that inactivation of the enzyme occurred as a result of the direct interaction of a quinone and/or semiquinone oxidation product with enzyme, as opposed to any effects of reactive oxygen species. Because acetylcholinesterase and dopamine are co-released from the neurons degenerating in Parkinson's disease, a direct chemical interaction between these two molecules could have significance both for the normal functioning of the substantia nigra and for related pathological states.
乙酰胆碱酯酶在中枢神经系统中发挥作用，与乙酰胆碱的水解无关。本研究探讨了这两种分子之间可能的相互作用：测试了乙酰胆碱酯酶对儿茶酚胺自氧化的影响，反过来，研究了多巴胺氧化产物对该酶催化活性的修饰。乙酰胆碱酯酶选择性地抑制了多巴胺生成醌的速度以及过氧化氢的积累，同时超氧化物的生成速率增加。吸收光谱分析揭示了一种新产物的形成，该产物在中性pH条件下将乙酰胆碱酯酶和多巴胺混合后出现。在所有情况下，丁酰胆碱酯酶均无作用。在多巴胺存在的情况下孵育乙酰胆碱酯酶会导致该酶的催化活性显著降低。应用修饰多巴胺自氧化的制剂（超氧化物歧化酶、过氧化氢酶、过氧化物酶）的效果表明，酶的失活是醌和/或半醌氧化产物与酶直接相互作用的结果，而不是活性氧的任何作用。由于乙酰胆碱酯酶和多巴胺是从帕金森病中退化的神经元共同释放的，这两种分子之间的直接化学相互作用可能对黑质的正常功能以及相关病理状态都具有重要意义。
