Document Detail

SULT1A3-mediated regiospecific 7-O-sulfation of flavonoids in Caco-2 cells can be explained by the relevant molecular docking studies.
MedLine Citation:
PMID:  22352375     Owner:  NLM     Status:  MEDLINE    
Flavonoids are polyphenolic compounds with various claimed health benefits, but the extensive metabolism by uridine-5'-diphospho-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) in liver and intestine led to poor oral bioavailabilities. The effects of structural changes on the sulfonation of flavonoids have not been systemically determined, although relevant effects of structural changes on the glucuronidation of flavonoids had. We performed the regiospecific sulfonation of sixteen flavonoids from five different subclasses of flavonoids, which are represented by apigenin (flavone), genistein (isoflavone), naringenin (flavanone), kaempherol (flavonol), and phloretin (chalcone). Additional studies were performed using 4 monohydroxyl flavonoids with a -OH group at the 3, 4', 5 or 7 position, followed by 5 dihydroxyl flavonoids, and 2 trihydroxyl flavonoids by using expressed human SULT1A3 and Caco-2 cell lysates. We found that these compounds were exclusively sulfated at the 7-OH position by SULT1A3 and primarily sulfated at the 7-OH position in Caco-2 cell lysates with minor amounts of 4'-O-sulfates formed as well. Sulfonation rates measured using SULT1A3 and Caco-2 cell lysates were highly correlated at substrate concentrations of 2.5 and 10 μM. Molecular docking studies provided structural explanations as to why sulfonation only occurred at the 7-OH position of flavones, flavonols and flavanones. In conclusion, molecular docking studies explain why SULT1A3 exclusively mediates sulfonation at the 7-OH position of flavones/flavonols, and correlation studies indicate that SULT1A3 is the main isoform responsible for flavonoid sulfonation in the Caco-2 cells.
Shengnan Meng; Baojian Wu; Rashim Singh; Taijun Yin; John Kenneth Morrow; Shuxing Zhang; Ming Hu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-16
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  9     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  2012-08-01     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  862-73     Citation Subset:  IM    
Department of Pharmaceutics, School of Pharmaceutical Sciences, China Medical University, Shenyang, Liaoning 110001, China.
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MeSH Terms
Apigenin / chemistry,  metabolism
Binding Sites
Caco-2 Cells
Flavanones / chemistry,  metabolism
Flavonoids / chemistry,  metabolism*
Genistein / chemistry,  metabolism
Kaempferols / chemistry,  metabolism
Phloretin / chemistry,  metabolism
Sulfotransferases / chemistry,  metabolism*
Tandem Mass Spectrometry
Grant Support
Reg. No./Substance:
0/Flavanones; 0/Flavonoids; 0/Kaempferols; 446-72-0/Genistein; 520-36-5/Apigenin; 60-82-2/Phloretin; EC 2.8.2.-/Sulfotransferases; EC phenol sulfotransferase; HN5425SBF2/naringenin

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