Roles of maize cytochrome P450 (CYP) enzymes in stereo-selective metabolism of hexabromocyclododecanes (HBCDs) as evidenced by in vitro degradation, biological response and in silico studies

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Roles of maize cytochrome P450 (CYP) enzymes in stereo-selective metabolism of hexabromocyclododecanes (HBCDs) as evidenced by in vitro degradation, biological response and in silico studies
	Huang, Honglin ; Wang, Dan ; Wen, Bei ; Lv, Jitao ; Zhang, Shuzhen
刊名	SCIENCE OF THE TOTAL ENVIRONMENT
	2019-03-15
卷号	656 页码:364-372
关键词	HBCDs Metabolism Maize Plant CYPs In vitro In silico
ISSN号	0048-9697
英文摘要	In vitro biotransformation of HBCDs by maize cytochrome P450 (CYP) enzymes, responses of CYPs to HBCDs at protein and transcription levels, and in silico simulation of interactions between CYPs and HBCDs were investigated in order to elucidate the roles of CYPs in the metabolism of HBCDs in maize. The results showed that degradation reactions of HBCDs by maize microsomal CYPs followed the first-order kinetics and were stereo-selective, with the metabolic rates following the order (-)gamma-> (+)gamma-> (+)alpha-> (-)alpha-HBCD. The hydroxylated metabolites OH-HBCDs, OH-PBCDs and OH-TBCDs were detected. (+)/(-)-alpha-HBCDs significantly decreased maize CYP protein content and inhibited CYP enzyme activity, whereas (+)/(-)-gamma-HBCDs had obvious effects on the induction of CYPs. HBCDs selectively mediated the gene expression of maize CYPs, including the isoforms of CYP71C3v2, CYP71C1, CYP81A1, CYP92A1 and CYP97A16. Molecular docking results suggested that HBCDs could bind with these five CYPs, with binding affinity following the order CYP71C3v2 < CYP81A1 < CYP97A16 < CYP92A1 < CYP71C1. The shortest distances between the Br-unsubstituted C atom of HBCD isomers and the iron atom of heme in CYPs were 4.18-11.7 angstrom, with only the distances for CYP71C3v2 being shorter than 6 angstrom (4.61-5.38 angstrom). These results suggested that CYP71C3v2 was an efficient catalyst for degradation of HBCDs. For (+)alpha- and (-)gamma-HBCDs, their binding affinities to CYPs were lower and the distances to the iron atom of heme in CYPs were shorter than their corresponding antipodes, consistent with the in vitro experimental results showing that they had shorter half-lives and were more easily hydroxylated. This study provides solid evidence for the roles of maize CYPs in the metabolism of HBCDs, and gives insight into the molecular mechanisms of the enantio-selective metabolism of HBCDs by plant CYPs. (C) 2018 Elsevier B.V. All rights reserved.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/43005]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
作者单位	1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, POB 2871, Beijing 100085, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Huang, Honglin,Wang, Dan,Wen, Bei,et al. Roles of maize cytochrome P450 (CYP) enzymes in stereo-selective metabolism of hexabromocyclododecanes (HBCDs) as evidenced by in vitro degradation, biological response and in silico studies[J]. SCIENCE OF THE TOTAL ENVIRONMENT,2019,656:364-372.
APA	Huang, Honglin,Wang, Dan,Wen, Bei,Lv, Jitao,&Zhang, Shuzhen.(2019).Roles of maize cytochrome P450 (CYP) enzymes in stereo-selective metabolism of hexabromocyclododecanes (HBCDs) as evidenced by in vitro degradation, biological response and in silico studies.SCIENCE OF THE TOTAL ENVIRONMENT,656,364-372.
MLA	Huang, Honglin,et al."Roles of maize cytochrome P450 (CYP) enzymes in stereo-selective metabolism of hexabromocyclododecanes (HBCDs) as evidenced by in vitro degradation, biological response and in silico studies".SCIENCE OF THE TOTAL ENVIRONMENT 656(2019):364-372.