Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior.
Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior.
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DOI：
10.1016/j.abb.2009.12.005
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发表时间：
2010-02-15
影响因子：
3.9
通讯作者：
Lockridge O
中科院分区：
文献类型：
--
作者：
Masson P;Lockridge O
丁酰胆碱酯酶是一种混杂的酶，表现出复杂的动力学行为。它在毒理学上很重要，因为它通过与有机磷毒物（OP）形成共价键来解毒OP。在此过程中OP和丁酰胆碱酯酶都被灭活。丁酰胆碱酯酶失活无不良影响。然而，神经突触中乙酰胆碱酯酶的失活可能是致命的。OP抑制丁酰胆碱酯酶和乙酰胆碱酯酶可以重新激活肟提供的OP没有老化。预防OP毒性的策略包括a）用OP清除剂处理，B）未老化酶与肟反应，c）老化酶的再激活，d）用外周位点配体减缓衰老，以及e）设计快速水解OP的突变体。选项（a）已通过人丁酰胆碱酯酶的I期临床试验取得进展。选项（B）为常规临床使用。其他的都在基础研究阶段。丁酰胆碱酯酶显示复杂的动力学行为，包括激活带正电荷的酯，水解酰胺的能力，和滞后时间（滞后）之前的水解苯甲酰胆碱和N-甲基吲哚乙酸。质谱法已经鉴定出在没有活性位点丝氨酸的蛋白质中酪氨酸和赖氨酸上的新的OP结合基序。有人提出，但尚未证明，低剂量暴露涉及OP修饰的蛋白质，没有活性位点丝氨酸。
Butyrylcholinesterase is a promiscuous enzyme that displays complex kinetic behavior. It is toxicologically important because it detoxifies organophosphorus poisons (OP) by making a covalent bond with the OP. The OP and the butyrylcholinesterase are both inactivated in the process. Inactivation of butyrylcholinesterase has no adverse effects. However inactivation of acetylcholinesterase in nerve synapses can be lethal. OP-inhibited butyrylcholinesterase and acetylcholinesterase can be reactivated with oximes provided the OP has not aged. Strategies for preventing the toxicity of OP include a) treatment with an OP scavenger, b) reaction of nonaged enzyme with oximes, c) reactivation of aged enzyme, d) slowing down aging with peripheral site ligands, and e) design of mutants that rapidly hydrolyze OP. Option (a) has progressed through phase I clinical trials with human butyrylcholinesterase. Option (b) is in routine clinical use. The others are at the basic research level. Butyrylcholinesterase displays complex kinetic behavior including activation by positively charged esters, ability to hydrolyze amides, and a lag time (hysteresis) preceding hydrolysis of benzoylcholine and N-methyl indoxyl acetate. Mass spectrometry has identified new OP binding motifs on tyrosine and lysine in proteins that have no active site serine. It is proposed, but not yet proven, that low dose exposure involves OP modification of proteins that have no active site serine.
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DOI：
10.1097/01.jom.0000235938.70212.dd
发表时间：
2006-10-01
影响因子：
3.2
作者：
Beseler, Cheryl;Stallones, Lorann;Kamel, Freya
通讯作者：
Kamel, Freya
影响因子：
3.4
作者：
Chatonnet, F;Boudinot, É;Foutz, AS
通讯作者：
Foutz, AS
影响因子：
3.8
作者：
Ashani, Y;Pistinner, S
通讯作者：
Pistinner, S
影响因子：
3.6
作者：
BEHRMAN, EJ;BIALLAS, MJ;ISAKS, M
通讯作者：
ISAKS, M
DOI：
10.1016/s0165-1838(98)00064-2
发表时间：
1998-07-15
期刊：
JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM
影响因子：
--
作者：
Darvesh, S;MacDonald, SE;Armour, JA
通讯作者：
Armour, JA