7-OH-flavone is sulfated in the human liver and duodenum, whereas 5-OH-flavone and 3-OH-flavone are potent inhibitors of SULT1A1 activity and 7-OH-flavone sulfation rate

Abstract

1. The aim of this investigation was to see whether 7-OH-flavone, 5-OH-flavone and 3-OH-flavone, which are present in edible vegetables, fruit and wine, are substrates or inhibitors of human liver and duodenum sulfotransferase. 2. An assay was set up to study the sulfation of 7-OH-flavone, and using this assay, it was observed that 7-OH-flavone was sulfated and the rate of sulfation (mean ± SD) was 324 ± 87 pmol min -1 mg -1 (liver) and 584 ± 164 pmol min -1 mg -1 (duodenum; p < 0.0001). 3. 7-OH-flavone sulfotransferase followed Michaelis-Menten kinetics and the K m (mean ± SD) was 0.2 ± 0.04 µM (liver) and 1.1 ± 0.3 µM (duodenum; p = 0.008). V max (mean ± SD) was 392 ± 134 pmol min -1 mg -1 (liver) and 815 ± 233 pmol min -1 mg -1 (duodenum; p = 0.016). 4. 5-OH-flavone and 3-OH-flavone were not sulfated and were inhibitors of human liver and duodenum SULT1A1 activity and 7-OH-flavone sulfation rate. 5. The IC50 of 5-OH-flavone for SULT1A1 was 0.3 ± 0.06 µM (liver) and 0.3 ± 0.1 µM (duodenum; n.s.) and those of 3-OH-flavone were 1.0 ± 0.1µM (liver) and 1.6 ± 0.03 µM (duodenum; p = 0.0006). 6. There was inhibition of 7-OH-flavone sulfation rate by 5-OH-flavone and 3-OH-flavone. The IC 50 of 5-OH-flavone for the sulfation rate of 7-OH-flavone was 3.5 ± 0.5 µM (liver) and 69 ± 18 µM (duodenum; p < 0.0001) and for 3-OH-flavone it was 18 ± 3.4 µM (liver) and 213 ± 47 µM (duodenum; p < 0.0001). 7. The position of the hydroxy group confers to the molecules of OH-flavones the quality of substrate or inhibitor of sulfotransferase.