Journal article
Hydroxylated polychlorinated biphenyls are substrates and inhibitors of human hydroxysteroid sulfotransferase SULT2A1
Chemical research in toxicology, Vol.19(11), pp.1420-1425
11/2006
DOI: 10.1021/tx060160+
PMID: 17112228
Abstract
Polychlorinated biphenyls (PCBs) are important persistent environmental contaminants. PCBs can be metabolically converted to their hydroxylated metabolites (OHPCBs), and in recent years, these OHPCBs have been observed to inhibit human sulfotransferases (SULTs) such as the phenol SULTs (SULT family-1) involved in the metabolism of estrogen and various other endogenous and xenobiotic phenols. In the present study, we have investigated the hypothesis that OHPCBs interact with family 2 hydroxysteroid (alcohol) SULTs (e.g., human SULT2A1), enzymes that are physiologically important for the metabolic transformations of several key endogenous hydroxysteroids as well as xenobiotic alcohols. We have examined the interactions of three OHPCBs with purified recombinant human SULT2A1 (also known as either human DHEA-ST or ST2A3). These studies with SULT2A1 were carried out on 4'-hydroxy-2,5-dichlorobiphenyl (4'-OH PCB 9), 4-hydroxy-2',3,5-trichlorobiphenyl (4-OH PCB 34), and 4'-hydroxy-2,3',4,5'-tetrachlorobiphenyl (4'-OH PCB 68). Our results showed that 4-OH PCB 34 and 4'-OH PCB 68 were substrates for SULT2A1, and 4-OH PCB 34 exhibited substrate inhibition similar to that seen with the physiological substrate dehydroepiandrosterone (DHEA). Although the sulfation of 4-OH PCB 34 and 4'-OH PCB 68 represents a potential metabolic route for these compounds, these OHPCBs may also compete with other xenobiotic substrates as well as endogenous substrates for SULT2A1. The third OHPCB studied, 4'-OH PCB 9, was not a substrate for SULT2A1 but was an inhibitor of the enzyme. Thus, the interactions of OHPCBs with human SULT2A1 represent both a potential route of metabolism and a possible source of interference with sulfation reactions catalyzed by this enzyme.
Details
- Title: Subtitle
- Hydroxylated polychlorinated biphenyls are substrates and inhibitors of human hydroxysteroid sulfotransferase SULT2A1
- Creators
- Yungang Liu - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USAT Idil ApakHans-Joachim LehmlerLarry W RobertsonMichael W Duffel
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.19(11), pp.1420-1425
- DOI
- 10.1021/tx060160+
- PMID
- 17112228
- NLM abbreviation
- Chem Res Toxicol
- ISSN
- 0893-228X
- eISSN
- 1520-5010
- Publisher
- United States
- Grant note
- P30 ES05605 / NIEHS NIH HHS R01 CA38683 / NCI NIH HHS P42 ES013661 / NIEHS NIH HHS K25 ES012475 / NIEHS NIH HHS
- Language
- English
- Date published
- 11/2006
- Academic Unit
- Molecular Physiology and Biophysics; Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984001080902771
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