Glucuronidation, a new metabolic pathway for pyrrolizidine alkaloids

doi:10.1021/tx900328f

	Glucuronidation, a new metabolic pathway for pyrrolizidine alkaloids
	He, Yu-Qi; Yang, Li; Liu, Hui-Xin; Zhang, Jiang-Wei; Liu, Yong; Fong, Alan; Xiong, Ai-Zhen; Lu, Yan-Liu; Yang, Ling; Wang, Chang-Hong
刊名	Chemical research in toxicology
	2010-03-15
卷号	23 期号:3 页码:591-9
ISSN号	1520-5010
DOI	10.1021/tx900328f
文献子类	Article
英文摘要	Pyrrolizidine 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.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266400]
专题	中国科学院上海药物研究所
作者单位	The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Road, Shanghai 201210, China
推荐引用方式 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):591-9.
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),591-9.
MLA	He, Yu-Qi,et al."Glucuronidation, a new metabolic pathway for pyrrolizidine alkaloids".Chemical research in toxicology 23.3(2010):591-9.