Document Detail


Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of salvianolic acid A.
MedLine Citation:
PMID:  22572482     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucuronidation is an important pathway in the elimination of salvianolic acid A (Sal A); however the mechanism of UDP-glucuronosyltransferases (UGTs) in this process remains to be investigated. In this study, the kinetics of Sal A glucuronidation by pooled human liver microsomes (HLMs), pooled human intestinal microsomes (HIMs) and 12 recombinant UGT isozymes were investigated. The glucuronidation of Sal A can be shown both in HLMs and HIMs with K(m) values of 39.84 ± 3.76 and 54.04 ± 4.36 µM, respectively. Among the 12 human UGTs investigated, UGT1A1 and UGT1A9 were the major isoforms that catalyzed the glucuronidation of Sal A (K(m) values of 29.72 ± 2.20 and 24.40 ± 2.60 µM). UGT1A9 showed the highest affinity of Sal A glucuronidation. Furthermore, a significant correlation between Sal A glucuronidation and propofol glucuronidation (a typical UGT1A9 substrate) was observed. The chemical inhibition study showed that the IC(50) for phenylbutazone inhibition of Sal A glucuronidation was 50.3 ± 4.3 and 39.4 ± 2.9 µM by HLMs and UGT1A9, respectively. Mefenamic acid inhibited Sal A glucuronidation in UGT1A1 and HLMs with IC(50) values of >200 and 12.4 ± 2.2 µM, respectively.
Authors:
De-en Han; Yi Zheng; Xijing Chen; Jiake He; Di Zhao; Shuoye Yang; Chunfeng Zhang; Zhonglin Yang
Publication Detail:
Type:  Journal Article     Date:  2012-04-27
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  27     ISSN:  1880-0920     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2012  
Date Detail:
Created Date:  2012-12-27     Completed Date:  2013-09-03     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  101164773     Medline TA:  Drug Metab Pharmacokinet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  579-85     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Caffeic Acids / metabolism,  pharmacokinetics*
Glucuronidase / metabolism
Glucuronosyltransferase / antagonists & inhibitors,  metabolism*
Humans
Hydrolysis / drug effects
Intestines / drug effects,  enzymology,  metabolism
Isoenzymes / metabolism
Kinetics
Lactates / metabolism,  pharmacokinetics*
Mefenamic Acid / pharmacology
Microsomes / drug effects,  enzymology,  metabolism
Microsomes, Liver / drug effects,  enzymology,  metabolism
Propofol / metabolism,  pharmacokinetics
Statistics as Topic
Chemical
Reg. No./Substance:
0/Caffeic Acids; 0/Isoenzymes; 0/Lactates; 367589PJ2C/Mefenamic Acid; 96574-01-5/salvianolic acid A; EC 2.4.1.-/UGT1A1 enzyme; EC 2.4.1.17/Glucuronosyltransferase; EC 2.4.1.17/UDP-glucuronosyltransferase 1A9; EC 3.2.1.31/Glucuronidase; YI7VU623SF/Propofol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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