In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 61, No. 2 ( 2010-01-08), p. 185-191
Abstract:
The aim of this study was to investigate the concentration-dependent sulfation of piceatannol, a dietary polyphenol present in grapes and wine and known for its promising anticancer and anti-inflammatory activity. Methods Sulfation of piceatannol was investigated in human liver cytosol as well as using a panel of recombinant sulfotransferase isoforms. Furthermore, the chemical structures of novel sulfates were identified by liquid chromatography/mass spectrometry (LC/MS). Key findings In the presence of 3′-phosphoadenosine-5′-phosphosulfate, three metabolites could be detected whose structures were identified by LC/MS/MS as piceatannol disulfate (M1) and two monosulfates (M2, M3). The kinetics of M1 formation exhibited a pattern of substrate inhibition with a Ki of 21.8 ± 11.3 μM and a Vmax/Km of 7.63 ± 1.80 μl/mg protein per min. Formation of M2 and M3 showed sigmoidal kinetics with apparent Km and Vmax values of 27.1 ± 2.90 μM and 118.4 ± 4.38 pmol/mg protein per min, respectively, for M2; and 35.7 ± 2.70 μM and 81.8 ± 2.77 pmol/mg protein per min, respectively, for M3. Incubation in the presence of human recombinant sulfotransferases (SULTs) demonstrated that M1 was formed equally by SULT1A1*1 and SULT1B1 and to a lesser extent by SULT1A1*2. M2 was preferentially catalysed by SULT1A1*2, 1A3 and 1E1. The formation of M3, however, was mainly catalysed by SULT1A2*1 and SULT1A3. Conclusions Our results elucidate the importance of piceatannol sulfation in human liver, which must be taken into account in humans after dietary intake of piceatannol.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
DOI:
10.1211/jpp.61.02.0007
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2010
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
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