The polymorphism of cholinesterases and its physiological significance
The polymorphism of cholinesterases and its physiological significance
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胆碱酯酶多态性及其生理意义
DOI：
10.1016/0968-0004(80)90014-6
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发表时间：
1980
影响因子：
13.8
通讯作者：
J. Massoulie
中科院分区：
文献类型：
--
作者：
J. Massoulie
乙酰胆碱酯酶和丁基胆碱酯酶在脊椎动物组织中以几种分子形式存在。在不对称的低盐聚集形式中，催化亚基连接到一个类似于胶原蛋白的“尾巴”上。这些分子似乎与细胞外基底膜有关，例如在神经肌肉连接处。其他无尾或球形的形式在大多数高等脊椎动物的组织中占主导地位，包括膜结合型和可溶性型。在整个脊椎动物中，这两种酶的不同形式之间存在明显的结构同源性。这种多态性可能确保了各种胆碱能结构的最佳功能。乙酰胆碱酯酶（EC 3.1）1.7)在胆碱能机制中起着至关重要的作用[1,2]，它能将乙酰胆碱快速水解成醋酸盐和胆碱。每个活性位点的周转率非常快（电鳗酶的周转率为1.5× 104 s-~，参见Rosenberry[3]的评论）。在大多数脊椎动物组织中，乙酰胆碱酯酶伴随着一种相关的酶，丁基胆碱酯酶或丙酰胆碱酯酶，这取决于物种。这种所谓的“伪”胆碱酯酶，或“非特异性”胆碱酯酶，在这里简称为胆碱酯酶。不同的分析方法，如电泳，表明乙酰胆碱酯酶和胆碱酯酶经常是异质的。在我们的实验室里，我们分析了这些酶在各种脊椎动物组织中的多态性。蔗糖梯度区离心法和分子筛色谱法根据其大小和形状分离出不同的组分。这些组分是稳定的分子实体，具有相当的催化活性。这样定义的各种分子形式对应于不同的四元结，但它们不一定是同质的，可能存在细微差异的变体，例如电荷。众所周知，乙酰胆碱酯酶和胆碱酯酶都是糖蛋白，因此，它们的糖部分的差异是可以预料的。在脊椎动物中，这两种胆碱酯酶在神经组织和肌肉中含量最多，但也存在于血清、红细胞、胎盘等组织中，其生理意义尚不清楚。正如Nachmansohn在1939年所认识到的，鱼的电子器官——比如
Acetylcholinesterase and butyrylcholinesterase occur under several molecular forms in vertebrate tissues. In the asymmetric, low-salt aggregating forms, the catalytic subunits are linked to a collasen-like'tail'. These molecules appear to be associated with extracellular basal lamina, eg in neuromuscular junction. Other tail-less, or globular, forms which are predominant in most tissues of higher vertebrates, include membrane-bound as well as soluble variants. There are clear structural homologies between the various forms of these two enzymes throughout the range of vertebrates. Such a polymorphism probably ensures an optimal functioning of various cholinergic structures.Acetylcholinesterase (EC 3.1. 1.7) plays an essential role in cholinergic mechanisms [1, 2], by rapidly hydrolysing acetylcholine into acetate and choline. The turnover rate per active site is extremely rapid (in the order of 1.5× 104 s-~ for the electric eel enzyme, see review by Rosenberry [3]). In most vertebrate tissues, acetylcholinesterase is accompanied by a related enzyme, butyrylcholinesterase or propionylcholinesterase depending upon the species. This so-called'pseudo'cholinesterase, or'nonspecific'cholinesterase, will be simply called here cholinesterase. Different methods of analysis, such as electrophoresis, have revealed that acetylcholinesterase and cholinesterase are frequently heterogeneous. In our laboratory, we have analysed the polymorphism of these enzymes in various vertebrate tissues. Zone centrifugation in sucrose gradients and molecular sieve chromatography separate distinct components according to their size and shape. These components are stable molecular entities and possess equivalent catalytic activities. The various molecular forms thus defined correspond to distinct quaternary associations, but they are not necessarily homogeneous and may present variants with minor differences, eg in their charge. It is known that acetylcholinesterase and cholinesterase are glycoproteins and, therefore, differences in their saccharidic moieties may be expected. In vertebrates, both cholinesterases are most abundant in nervous tissue and muscles, but are also present in serum, erythrocytes, placenta and other tissues where their physiological significance is not clear. As recognized in 1939 by Nachmansohn, the electric organs of fishes-such as