T-2 毒素被鸡 CYP3A37 羟化。

T-2 toxin is hydroxylated by chicken CYP3A37.

机构信息

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Food Chem Toxicol. 2013 Dec;62:622-7. doi: 10.1016/j.fct.2013.09.031. Epub 2013 Sep 30.

DOI:10.1016/j.fct.2013.09.031

PMID:24090734

Abstract

T-2 toxin (T-2) is an acute toxic trichothecene mycotoxin produced mainly by Fusarium species, detected in many crops including oats, wheat and barley, in animal feed and food. It is important to know the metabolic pathway and kinetics of T-2 in food animals given that T-2 can cause serious adverse effects on human health. In this study, we investigated the metabolic capacity of chicken CYP3A37 in the metabolism of T-2 using reconstituted bacteria produced enzymes. Our results showed that chicken CYP3A37 is able to convert T-2 to 3'-OH T-2 with an apparent Km of 15.29 μM, and T-2 hydroxylation activity of CYP3A37 is strongly inhibited by ketoconazole (IC50=0.11 μM). We also observed that chicken CYP3A37 can catalyze erythromycin N-demethylation, another CYP3A-specific activity. These findings imply that chicken CYP3A37 may have a broad substrate spectrum, similar to its human homologue CYP3A4.

摘要

T-2 毒素（T-2）是一种由镰刀菌属产生的急性毒性单端孢霉烯类真菌毒素，在燕麦、小麦和大麦等多种作物、动物饲料和食品中均有检出。了解 T-2 在食用动物体内的代谢途径和动力学非常重要，因为 T-2 可对人类健康造成严重不良影响。在这项研究中，我们使用重组细菌产生的酶，研究了鸡 CYP3A37 对 T-2 代谢的代谢能力。结果表明，鸡 CYP3A37 能够将 T-2 转化为 3'-OH T-2，其表观 Km 为 15.29 μM，并且 CYP3A37 的 T-2 羟化活性受到酮康唑（IC50=0.11 μM）的强烈抑制。我们还观察到鸡 CYP3A37 可以催化红霉素 N-去甲基化，这是另一种 CYP3A 特异性活性。这些发现表明，鸡 CYP3A37 可能具有广泛的底物谱，与其人类同源物 CYP3A4 相似。