1 research outputs found
SULT1A3-Mediated Regiospecific 7-O-Sulfation of Flavonoids in Caco-2 Cells Can Be Explained by the Relevant Molecular Docking Studies
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′-<i>O</i>-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