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Drug Metabolism and Disposition Fast Forward
First published on February 9, 2007; DOI: 10.1124/dmd.106.013987


0090-9556/07/3505-740-746$20.00
DMD 35:740-746, 2007

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Variable Sulfation of Dietary Polyphenols by Recombinant Human Sulfotransferase (SULT) 1A1 Genetic Variants and SULT1E1

Din Ung, and Swati Nagar

Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania

Human cytosolic sulfotransferases (SULTs) catalyze the sulfate conjugation of several important endo- and xenobiotics. Among the superfamily of SULT enzymes, SULT1A1 catalyzes the sulfation of small planar phenolic compounds, whereas SULT1E1 has a major role in estrogen conjugation. The human SULT1A1 gene has common single nucleotide polymorphisms that define three allozymes, SULT1A1*1, *2, and *3. The enzyme kinetics of SULT1A1 allozymes and SULT1E1 were characterized for the polyphenolic substrates apigenin, chrysin, epicatechin, quercetin, and resveratrol. Purified recombinant SULT proteins were generated in a baculoviral-insect cell system, and incubated in vitro with each substrate to determine catalytic activity. The effect of polyphenol sulfation was examined in mammalian cell lines stably expressing SULT1E1. For all polyphenols investigated, "normal-activity" SULT1A1*1 allozyme had significantly greater Vmax estimates than SULT1E1, and allele-specific differences in SULT1A1-mediated sulfation were observed. The polymorphic SULT1A1*2 allozyme exhibited low activity toward apigenin, epicatechin, and resveratrol. SULT1A1*1 and *3 acted as normal-activity allozymes for these substrates. Altered cellular proliferation was observed in MCF-7 cells stably expressing SULT1E1 upon treatment with chrysin, quercetin, or resveratrol, thus suggesting inactivation of these compounds by SULT1E1. These results suggest an important role for SULT isozymes and their pharmacogenetics in polyphenol disposition.


Address correspondence to: Dr. Swati Nagar, Temple University School of Pharmacy, 3307 North Broad St., Philadelphia PA 19140. E-mail: swati.nagar{at}temple.edu




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