Inhibition of phenol sulfotransferase (SULT1A1) by quercetin in human adult and foetal livers

C. De Santi, A. Pietrabissa, F. Mosca, A. Rane, G. M. Pacifici

Research output: Contribution to journalArticlepeer-review

Abstract

1. Quercetin is one of the most abundant flavonoids in edible vegetables, fruit and wine. The aim was to study the type of inhibition of SULT1A1 by quercetin in the human adult and foetal livers. 2. The activity of SULT1A1 was measured with 4μM 4-nitrophenol and 0.4 μM 3′-phosphoadenosine-5′-phosphosulphate-[35S], and its mean (±SD) and median were 769 ± 311 and 740 pmol min-1 mg-1, respectively (adult liver, n = 10), and 185 ± 98 and 201 pmol min-1 mg-1, respectively (foetal liver, n = 8, p <0.0001). 3. In non-inhibited samples, Km for SULT1A1 (mean ± SD) was 0.314 ± 0.14 μM (adult liver) and 0.49 ± 0.17 μM (foetal liver, n.s.). Vmax for SULT1A1 (mean ± SD) was 885 ± 135 pmol min-1 mg-1 (adult liver) and 267 ± 93 pmol min-1 mg-1 (foetal liver, p = 0.007). 4. The IC50 of quercetin for SULT1A1 was measured in three samples of adult and foetal livers and was 13 ± 2.1 and 12 ± 1.4 nM, respectively. 5. The type of inhibition was mixed non-competitive in adult and foetal livers and Ki was 4.7 ± 2.5 nM (adult liver) and 4.8 ± 1.6 nM (foetal liver). 6. In the adult liver, the intrinsic clearance (mean ± SD) was 3.3 ± 1.5 ml min-1 mg-1 (non-inhibited samples), 0.9 ± 0.4 ml min-1 mg-1 (12.5 nM quercetin) and 0.54 ± 0.06 ml min-1 mg-1 (25 nM quercetin). In the foetal liver, the intrinsic clearance (mean ± SD) was 0.5 ± 0.2 ml min-1 mg-1 (non-inhibited samples), 0.12 ± 0.01 ml min-1 mg-1 (12.5 nM quercetin) and 0.2 ± 0.09 ml min-1 mg-1 (25 nM quercetin). 7. In conclusion, quercetin is a potent inhibitor of human adult and foetal liver SULT1A1. It reduces the sulphation rate and intrinsic clearance of 4-nitrophenol in both human adult and foetal livers. This suggests that quercetin may inhibit the sulfation rate of those drugs sulphated by SULT1A1. The inhibition of SULT1A1 is complex and not due solely to competition at the catalytic site of SULT1A1.

Original languageEnglish
Pages (from-to)363-368
Number of pages6
JournalXenobiotica
Volume32
Issue number5
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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