DICP OpenIR
Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids
He, Yu-Qi1; Yang, Li1; Liu, Hui-Xin2; Zhang, Jiang-Wei2; Liu, Yong2; Fong, Alan3; Xiong, Ai-Zhen1; Lu, Yan-Liu1; Yang, Ling2; Wang, Chang-Hong1; Wang, Zheng-Tao1
Source PublicationCHEMICAL RESEARCH IN TOXICOLOGY
2010-03-01
DOI10.1021/tx900328f
Volume23Issue:3Pages:591-599
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
WOS SubjectChemistry, Medicinal ; Chemistry, Multidisciplinary ; Toxicology
WOS Research AreaPharmacology & Pharmacy ; Chemistry ; Toxicology
WOS KeywordHUMAN UDP-GLUCURONOSYLTRANSFERASES ; MESSENGER-RNA EXPRESSION ; HUMAN LIVER-MICROSOMES ; SPECIES-DIFFERENCES ; N-GLUCURONIDATION ; RAT ; MONOCROTALINE ; ACTIVATION ; PLANTS
AbstractPyrrolizidine alkaloids (PAS) possess significant hepatotoxicity to humans and animals after metabolic activation by liver P450 enzymes. Metabolism pathways of PAs have been studied for several decades, including metabolic activation, hydroxylation, N-oxidation, and hydrolysis. However, the glucuronidation of intact PAs has not been investigated, although glucuronidation plays an important role in the elimination and detoxication of xenobiotics. In this study, PAs glucuronidation was investigated, and three important points were found. First, we demonstrated that senecionine (SEN)-a representative hepatotoxic PA-could be conjugated by glucuronic acid via an N-glucuronidation reaction catalyzed by uridine diphosphate glucuronosyl transferase in human liver microsomes. Second, glucuronidation of SEN was catalyzed not only by human but also other animal species and showed significant species differences. Rabbits, cattle, sheep, pigs. and humans showed the significantly higher glucuronidation activity than mice. rats, dogs, and guinea pigs on SEN. Kinetics of SEN glucuronidation in humans, pigs, and rabbits followed the one-site binding model of the Michaelis-Menten equation, while cattle and sheep followed the two-sites binding model of the Michaelis-Menten equation. Third, besides SEN, other hepatotoxic PAs including monocrotaline, adonifoline, and isoline also underwent N-glucuronidation in humans and several animal species such as rabbits, cattle, sheep, and pigs.
Language英语
WOS IDWOS:000275411700020
Citation statistics
Cited Times:16[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/141648
Collection中国科学院大连化学物理研究所
Affiliation1.Shanghai Univ Tradit Chinese Med, MOE Key Lab Standardizat Chinese Med, Inst Chinese Mat Med, Shanghai 201210, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
3.Sarawak Gen Hosp, Clin Res Ctr, Kuching 93000, Malaysia
Recommended Citation
GB/T 7714
He, Yu-Qi,Yang, Li,Liu, Hui-Xin,et al. Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2010,23(3):591-599.
APA He, Yu-Qi.,Yang, Li.,Liu, Hui-Xin.,Zhang, Jiang-Wei.,Liu, Yong.,...&Wang, Zheng-Tao.(2010).Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids.CHEMICAL RESEARCH IN TOXICOLOGY,23(3),591-599.
MLA He, Yu-Qi,et al."Glucuronidation, a New Metabolic Pathway for Pyrrolizidine Alkaloids".CHEMICAL RESEARCH IN TOXICOLOGY 23.3(2010):591-599.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[He, Yu-Qi]'s Articles
[Yang, Li]'s Articles
[Liu, Hui-Xin]'s Articles
Baidu academic
Similar articles in Baidu academic
[He, Yu-Qi]'s Articles
[Yang, Li]'s Articles
[Liu, Hui-Xin]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[He, Yu-Qi]'s Articles
[Yang, Li]'s Articles
[Liu, Hui-Xin]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.