有机磷酸酯诱发的迟发性神经病靶标酯酶的老化机制

Mechanism of aging of organophosphate-induced delayed neuropathy target esterase

神经病靶标酯酶的老化被认为是有机磷酸酯诱发迟发性神经病的必需步骤。老化的本质是酶分子中的丝氨酸活性位点共价结合的磷酰基脱烷基化,使得酶不可能再复活,但其过程不同于乙酰胆碱酯酶的老化过程,并受有机磷酸酯的构型和纯度的影响。近来研究表明,不同的有机磷酸酯对其老化的机制不一样,存在着可逆的质子丢失和侧链基团的分子内转移两条途径,并推测Asp1044和Asp1004可能是侧链基团转移的结合位点,然而神经病靶标酯酶的老化机制的完全阐明还需要进一步的分子实验证据。

Aging of neuropathy target esterase （NTE） has been considered as an essential step for inducing organophosphate-induced delayed neumpathy. The essence of NTE aging is dealkylation of phosphoryl moiety which has covalently attached to the active site serine, the dealkylated phosphoryl group can not be readily detached from NTE and renders the inhibited enzyme intractable to reactivation. However, the mechanism of aging of NTE is different from that of acetylcholinesterase, and is affected by the stereochemistry and purity of organophosphates. Recent studies suggested that there be different pathway of NTE aging caused by different organophosphates, such as reversible proton loss and intramolecular tranferring of the side-group; the side-group was perhaps attached to Asp^1044 and Asp^1004. However, further mole- cular evidences are needed to reveal the mechanism of the aging of NTE.