title: Sulfation of iodothyronines by recombinant human liver steroid sulfotransferases.
abstract: Sulfation is an important pathway in the metabolism of thyroid hormones. Sulfated iodothyronines are elevated in nonthyroidal illnesses and in the normal human fetal circulation. We assayed and characterized COS-1 cell expressed recombinant human liver dehydroepiandrosterone sulfotransferase (DHEA ST or SULT2A1) and estrogen sulfotransferase (EST or SULT1E1) activities for the first time with triiodothyronine (T(3)) as the substrate. Several biochemical properties that included apparent K(m) values, thermal stabilities, and responses to the inhibitors 2, 6-dichloro-4-nitrophenol and NaCl were tested. SULT2A1, a member of the hydroxysteroid sulfotransferase family, used 3,3'-T(2) more readily than T(3) and 3,5-T(2) as substrates, but had the lowest apparent K(m) value for T(3) of any reported human SULT. SULT1E1, a member of the phenol sulfotransferase family, used 3,3'-T(2) and rT(3) more readily than T(3), and also displayed the greatest specificity for T(4) among human SULTs. SULT2A1 may contribute more to iodothyronine sulfation than previously suspected. Potential roles of both steroid sulfotransferases in the enhanced sulfation of nonthyroidal illnesses and fetal development invite further investigation.
authors.affiliation: Creighton University School of Medicine, Omaha, Nebraska 68105, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: R J
authors.initials: RJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D015239:Arylsulfotransferase / Q000378:metabolism; D019556:COS Cells; D006801:Humans; D007700:Kinetics; D011994:Recombinant Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000378:metabolism*; D013816:Thermodynamics; D013970:Thyronines / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D014162:Transfection
chemical_list: D011994:Recombinant Proteins; D013970:Thyronines; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase; D015239:Arylsulfotransferase; C020122:estrone sulfotransferase; D013974:Thyroxine