INTERACTION OF SOME TRIALKYL PHOSPHOROTHIOLATES WITH ACETYLCHOLINESTERASE - CHARACTERIZATION OF INHIBITION, AGING AND REACTIVATION
INTERACTION OF SOME TRIALKYL PHOSPHOROTHIOLATES WITH ACETYLCHOLINESTERASE - CHARACTERIZATION OF INHIBITION, AGING AND REACTIVATION
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DOI：
10.1016/0005-2744(81)90175-3
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发表时间：
1981-01-01
期刊：
影响因子：
--
通讯作者：
REINER, E
中科院分区：
文献类型：
--
作者：
CLOTHIER, B;JOHNSON, MK;REINER, E
本文研究了牛红细胞乙酰胆碱酯酶（acetylcholine acetylhydrolase, EC 3.1.1.7）与一组结构相关的磷硫酸盐[有机磷杀虫剂]的反应，以研究磷酸化酶的性质并鉴定其离去基。OOS-和OOS-三甲基磷硫酸盐及其三乙基类似物对乙酰胆碱酯酶具有可逆性和进行性抑制作用，磷酸化酶经历自发再激活和老化。每个化合物的酶抑制剂Kd和抑制速率常数（ka），再激活和老化。oss -化合物是比oos -化合物更有效的抑制剂，并且衍生的抑制酶重新激活和老化更快。与已知结构的磷酸化酶的再活化和老化速率常数比较表明，磷酸化过程中的离去基为s -烷基。sss -三甲基和-三乙基磷硫酸盐也形成可逆复合物并逐渐抑制酶。使用这些抑制剂，磷酸化酶既不能自发地重新激活，也不能在其他抑制剂成功的条件下响应肟。ka值（37度）。C, pH 7.4)范围为30 M-1。min-1 （oos -三甲基磷硫酸酯）至6.7 .cntdot。103 M-1 .cntdot。min-1 （oss -三乙基磷硫酸酯）与1.25-105 M-1相比。min-1测定了异丙硫磷（O，S-二甲基S-（1,2-二乙氧基乙基）-磷二硫酸盐），该化合物作为1个参比化合物。如果三烷基磷硫酸盐的抑制效力是在固定的预孵育时间后通过测量来计算的，那么ka值的结果将会产生误导。
The reaction of bovine erythrocyte acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) with a set of structurally related phosphorothiolates [organophosphorus insecticides] was studied in order to investigate the properties of the phosphorylated enzymes and to identify the leaving group. OOS- and OOS-trimethyl phosphorothiolates and their triethyl analogs inhibit acetylcholinesterase reversibly and by progressive inhibition, and the phosphorylated enzymes undergo both spontaneous reactivation and aging. For each compound the enzyme-inhibitor Kd and the rate constants for inhibition (ka), reactivation and aging were derived. The OSS-compounds are more potent inhibitors than the OOS-compounds, and the derived inhibited enzymes reactivate and age faster. Comparison of reactivation and aging rate constants with those obtained from phosphorylated enzymes of known structure showed that the leaving group during phosphorylation is the S-alkyl. SSS-trimethyl and -triethyl phosphorothiolates also form reversible complexes and inhibit the enzyme progressively. With these inhibitors the phosphorylated enzymes did not reactivate either spontaneously or in response to oximes under conditions successful for the other inhibitors. The ka values (37.degree. C, pH 7.4) range from 30 M-1 .cntdot. min-1 (OOS-trimethyl phosphorothiolate) to 6.7 .cntdot. 103 M-1 .cntdot. min-1 (OSS-triethyl phosphorothiolate) as compared to 1.25-105 M-1 .cntdot. min-1 determined for isomalathion (O,S-dimethyl S-(1,2-dicarbethoxyethyl)-phosphorodithioate), which was used as 1 of the reference compounds. If the inhibitory potency of the trialkyl phosphorothiolates is calculated from measurements made after a fixed preincubation time, the results in ka values will be misleading.