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与眼镜蛇毒液乙酰胆碱酯酶相关的高芳酰基酰胺酶活性:生物学意义。

High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.

机构信息

Animal Genomics and Bioinformatics Division, Department of Livestock, Biotechnology & Environment, National Institute of Animal Science, Suwon 441-706, South Korea.

出版信息

Biochimie. 2009 Nov-Dec;91(11-12):1450-6. doi: 10.1016/j.biochi.2009.08.004. Epub 2009 Aug 19.

Abstract

Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (AAA) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of AAA activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes. Remarkably cobra venom showed the highest AAA activity and also high AAA/AChE ratio. Both serotonergenic and cholinergic inhibitors inhibited the cobra venom AAA activity in a concentration dependent manner, which also underlines the association of AAA with AChE of cobra venom. The study becomes interesting because of i) the cobra venom AChE exists in monomeric globular forms; ii) in Alzheimer's disease too the most abundant forms of cholinesterases are monomeric globular forms, thought to be involved in the pathogenesis of Alzheimer's disease; iii) the effect of Alzheimer's disease drugs on the AAA activity of cobra venom, indicated that AAA activity of cobra venom was more sensitive than AChE and iv) Huperzine and Tacrine showed more pronounced effect on AAA. Thus, this study elucidates the high AAA associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources were found to have lower activity.

摘要

过去三十年来,人们一直对研究胆碱酯酶(ChE)的非经典功能感兴趣。其中之一是与 ChE 相关的芳基酰基酰胺酶(AAA)活性,但在体外表现为一种酶,可以分解人工底物邻硝基乙酰苯胺,其生理功能未知。在本研究中,我们比较了不同来源的 AChE(如山羊脑、电鳗器官和不同蛇的毒液)的 AAA 活性水平。值得注意的是,眼镜蛇毒液显示出最高的 AAA 活性和高 AAA/AChE 比值。5-羟色胺能和胆碱能抑制剂以浓度依赖的方式抑制眼镜蛇毒液 AAA 活性,这也强调了 AAA 与眼镜蛇毒液 AChE 的关联。这项研究之所以有趣,是因为:i)眼镜蛇毒液 AChE 以单体球状形式存在;ii)在阿尔茨海默病中,最丰富的胆碱酯酶形式也是单体球状形式,被认为与阿尔茨海默病的发病机制有关;iii)阿尔茨海默病药物对眼镜蛇毒液 AAA 活性的影响表明,眼镜蛇毒液 AAA 活性比 AChE 更敏感;iv)石杉碱甲和他克林对 AAA 的作用更明显。因此,这项研究阐明了与眼镜蛇毒液 AChE 相关的高 AAA 可能成为测试 AD 药物药理作用的突出活性之一,因为其他来源的活性较低。

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