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.
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 microM (liver) and 1.1 +/- 0.3 microM (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 microM (liver) and 0.3 +/- 0.1 microM (duodenum; n.s.) and those of 3-OH-flavone were 1.0 +/- 0.1 microM (liver) and 1.6 +/- 0.03 microM (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 microM (liver) and 69 +/- 18 microM (duodenum; p < 0.0001) and for 3-OH-flavone it was 18 +/- 3.4 microM (liver) and 213 +/- 47 microM (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.
Vietri
M
M
Department of Neurosciences, Section of Pharmacology, Medical School, Via Roma 55, I-56126 Pisa, Italy.
Pietrabissa
A
A
Spisni
R
R
Mosca
F
F
Pacifici
G M
GM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015239:Arylsulfotransferase; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013379:Substrate Specificity; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D005419:Flavonoids; D013431:Sulfates; C062711:5-hydroxyflavone; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C429845:7-hydroxyflavone; C041477:3-hydroxyflavone