Δ4-3-Ketosteroids as a New Class of Substrates for the Cytosolic Sulfotransferases

Publication date: Available online 3 August 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Takuyu Hashiguchi, Katsuhisa Kurogi, Takehiko Shimohira, Takamasa Teramoto, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara
Cytosolic sulfotransferase (SULT)-mediated sulfation is generally known to involve the transfer of a sulfonate group from the active sulfate, 3′-phosphoadenosine 5′-phosphosulfate (PAPS), to a hydroxyl group or an amino group of a substrate compound. We report here that human SULT2A1, in addition to being able to sulfate dehydroepiandrosterone (DHEA) and other hydroxysteroids, could also catalyze the sulfation of Δ⁴–3-ketosteroids, which carry no hydroxyl groups in their chemical structure. Among a panel of Δ⁴–3-ketosteroids tested as substrates, 4-androstene-3,17-dione and progesterone were found to be sulfated by SULT2A1. Mass spectrometry analysis and structural modeling supported a reaction mechanism which involves the isomerization of Δ⁴–3-ketosteroids from the keto form to an enol form, prior to being subjected to sulfation. Results derived from this study suggested a potential role of SULT2A1 as a Δ⁴–3-ketosteroid sulfotransferase in steroid metabolism.



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