Kinetic characterization of an efficient cocaine hydrolase against toxic metabolites of cocaine.
Kinetic characterization of an efficient cocaine hydrolase against toxic metabolites of cocaine.
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针对可卡因有毒代谢物的有效可卡因水解酶的动力学表征。
DOI：
10.1039/d3ob00374d
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发表时间：
2023
影响因子：
3.2
通讯作者：
Zheng,Fang
中科院分区：
文献类型：
--
作者：
Zhan,Max;Hou,Shurong;Shang,Linyue;Chen,Xiabin;Zhan,Chang-Guo;Zheng,Fang
在酒精存在的情况下，可卡因代谢产生许多代谢物，包括三种有毒代谢物（可卡因、去甲可卡因和去甲可卡因），它们的毒性都比可卡因本身更大，毒性顺序为可卡因<可卡因<去甲可卡因<去甲可卡因<去甲可卡因。在这项研究中，我们对我们之前报道的可卡因水解酶（E30-6）进行了动力学分析，与可卡因相比，它的催化活性加速了三种有毒代谢物的水解。根据获得的动力学数据，该酶对这些底物的体外催化效率依次为：可卡因>可卡因>诺可卡因>诺可卡因。体外和体内实验证明，E30-6不仅能有效地加速可卡因本身的水解，还能有效地加速三种毒性代谢物的水解。据我们目前所知，E30-6是所有报道的酶中对这些有毒底物（可卡因、可卡因、去甲可卡因和去甲可卡因）最有效的酶。这些发现表明，E30-6即使同时使用酒精和可卡因，也能有效地治疗可卡因毒性。
In the presence of alcohol, cocaine metabolism produces a number of metabolites, including three toxic ones (cocaethylene, norcocaine, and norcocaethylene) which are all more toxic than cocaine itself, with the toxicity in the order of cocaine < cocaethylene < norcocaine < norcocaethylene. In this study, we performed kinetic analysis on our previously reported cocaine hydrolase (E30-6) for its catalytic activities accelerating the hydrolysis of the three toxic metabolites in comparison with cocaine. Based on the obtained kinetic data, the in vitro catalytic efficiencies of the enzyme against these substrates are in the order of cocaine > cocaethylene > norcocaine > norcocaethylene. It has been demonstrated that E30-6 can efficiently accelerate the hydrolysis of not only cocaine itself, but also all three toxic metabolites in vitro and in vivo. E30-6 is the most efficient enzyme for each of these toxic substrates (cocaine, cocaethylene, norcocaine, and norcocaethylene) among all the reported enzymes as far as we know at this point. These findings suggest that E30-6 is capable of efficiently treating cocaine toxicity even when alcohol and cocaine are used concurrently.