title: Sulfation of "estrogenic" alkylphenols and 17beta-estradiol by human platelet phenol sulfotransferases.
abstract: We have investigated the ability of alkylphenols to act as substrates and/or inhibitors of phenol sulfotransferase enzymes in human platelet cytosolic fractions. Our results indicate: (i) straight chain alkylphenols do not interact with the monoamine-sulfating phenol sulfotransferase (SULT1A3); (ii) short chain 4-n-alkylphenols (C < 8) are substrates for the phenol-sulfating enzymes (SULT1A1/2), which exhibit two activity maxima against substrates with alkyl chain lengths of C1-2 and C4-5; (iii) long chain 4-n-substituted alkylphenols (C >/= 8) are poor substrates and act as inhibitors of SULT1A1/2; (iv) human platelets contain two activities, of low and high affinity, capable of sulfating 17beta-estradiol, and 4-n-nonylphenol is a partial mixed inhibitor of the low affinity form of this activity. We conclude that by acting either as substrates or inhibitors of SULT1A1/2, alkylphenols may influence the sulfation, and hence the excretion, of estrogens and other phenol sulfotransferase substrates in humans.
authors.affiliation: School of Biosciences, the University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
authors.forename: R M
authors.initials: RM
authors.lastname: Harris
authors.forename: R H
authors.initials: RH
authors.lastname: Waring
authors.forename: C J
authors.initials: CJ
authors.lastname: Kirk
authors.forename: P J
authors.initials: PJ
authors.lastname: Hughes
mesh_terms: D000473:Alkanes / Q000378:metabolism* / Q000494:pharmacology; D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001792:Blood Platelets / Q000201:enzymology*; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D009596:Nitrophenols / Q000378:metabolism; D010636:Phenols / Q000378:metabolism* / Q000494:pharmacology; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000378:metabolism
chemical_list: D000473:Alkanes; D004967:Estrogens; D009596:Nitrophenols; D010636:Phenols; D013463:Sulfuric Acid Esters; D004958:Estradiol; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C403170:monoamine-sulfating phenol sulfotransferase; C024836:4-nitrophenol