In Vitro Characterization of Glucuronidation of Vanillin: Identification of Human UDP-Glucuronosyltransferases and Species Differences
Vanillin is a food flavoring agent widely utilized in foods, beverages, drugs, and perfumes and has been demonstrated to exhibit multiple pharmacological activities. Given the importance of glucuronidation in the metabolism of vanillin, the UDP‐glucuronosyltransferase conjugation pathway of vanillin...
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Published in | Phytotherapy research Vol. 27; no. 9; pp. 1392 - 1397 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.09.2013
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Vanillin is a food flavoring agent widely utilized in foods, beverages, drugs, and perfumes and has been demonstrated to exhibit multiple pharmacological activities. Given the importance of glucuronidation in the metabolism of vanillin, the UDP‐glucuronosyltransferase conjugation pathway of vanillin was investigated in this study. Vanillin glucuronide was identified by high‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) and a hydrolysis reaction catalyzed by β‐glucuronidase. The kinetic study showed that vanillin glucuronidation by HLMs and HIMs followed Michaelis‐Menten kinetics and the kinetic parameters were as follows: 134.9 ± 13.5 μM and 81.3 ± 11.3 μM for Km of HLMs and HIMs, 63.8 ± 2.0 nmol/min/mg pro and 13.4 ±2.0 nmol/min/mg pro for Vmax of HLMs and HIMs. All UDP‐glucuronosyltransferase (UGT) isoforms except UGT1A4, 1A9, and 2B7 showed the capability to glucuronidate vanillin, and UGT1A6 exerted the higher Vmax/Km values than other UGT isoforms for the glucuronidation of vanillin when assuming expression of isoforms is similar in recombinant UGTs. Kinetic analysis using liver microsomes from six studied speices indicated that vanillin had highest affinity for the monkey liver microsomes enzyme (Km = 25.6 ± 3.2 μM) and the lowest affinity for the mice liver microsomes enzyme (Km = 149.1 ± 18.4 μM), and intrinsic clearance was in the following order: monkey > dog > minipig > mice > rat ~ human. These data collectively provided important information for understanding glucuronidation of vanillin. Copyright © 2012 John Wiley & Sons, Ltd. |
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Bibliography: | ark:/67375/WNG-9JC1QNCV-7 Supporting InformationSupporting information may be found in the online version of this article. ArticleID:PTR4885 istex:EADC35EC355F68077FF7633DAF46E7443FB30F53 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0951-418X 1099-1573 |
DOI: | 10.1002/ptr.4885 |