CYP1A2
化学
羟基化
代谢途径
毒性
体内
酒
药理学
新陈代谢
双键
立体化学
生物化学
侧链
细胞色素P450
酶
生物
有机化学
遗传学
聚合物
作者
Guode Zhao,Yufei Ma,Xu Wang,Wei Li,Yuqin Chen,Weiwei Li,Ying Peng,Jiang Zheng
标识
DOI:10.1021/acs.jafc.2c07555
摘要
α-Asarone (αA) and β-asarone (βA) are often used as flavoring agents for alcoholic beverages and food supplements. They possess a double bond in the side chain with different configurations. Double bonds are a class of alert chemical group, due to their metabolic epoxidation to the corresponding epoxides eliciting liver injury. Little is known about changes of configuration on metabolic activation and related toxicity. Here, we report the insight into the mechanisms of hepatotoxicity of asarone with different configurations. In vitro and in vivo comparative studies demonstrated βA displayed higher metabolic activation effectiveness. Apparently, the major metabolic pathway of βA underwent epoxidation at C-1' and C-2', while αA was mainly metabolized to the corresponding alcohol resulting from the hydroxylation of C-3'. CYP1A2 dominated the metabolism of αA and βA. The molecular simulation studies showed that the orientation of βA at the active site of CYP1A2 favored the epoxidation of βA over that of αA. These findings not only remind us that configuration is another important factor for toxicities but also facilitate the understanding of the mechanisms of toxic action of asarone. Additionally, these findings would benefit the risk assessment of αA and βA exposure from foods.
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