caa a22 4500 469078731 CHVBK 20180323132943.0 cr unu---uuuuu 170328e19920801xx s 000 0 eng 10.1007/BF00165306 doi (NATIONALLICENCE)springer-10.1007/BF00165306 Hydroxysteroid sulfotransferase and a specific UDP-glucuronosyltransferase are involved in the metabolism of digitoxin in man [Elektronische Daten] [Achim Schmoldt, Ingbert Blömer, Andrea Johannes] Summary: In vitro experiments were performed with cytosolic and microsomal fractions of human liver specimens in order to investigate which enzyme forms of sulfotransferase (ST) and UDP-glucurosyltransferase (GT) are involved in the metabolism of digitoxin (dt-3) and/or its cleavage products. It was found that the cytosolic STs preferentially react with digitoxigenin (dt-0) whereas microsomal GTs conjugate digitoxigenin-monodigitoxoside (dt-1) and in traces the bisdigitoxoside (dt-2). Dt-3 and dt-0 cannot be glucuronidated. By separation of different sulfotransferases it was found that the hydroxysteroid-ST is responsible for dt-0 and 3-epidigitoxigenin (epi-dt-0) sulfation. The hydroxysteroid-ST could be purified and characterized (apparent Km and Vmax for dt-0 sulfation: approx. 17 μmol/l and 2.7 nmol/min mg protein, respectively). Of various model substrates and endogenous compounds (steroids, bilirubin) none caused a competitive inhibition of the microsomal dt-1 glucuronidation except dt-2 and dt-3. Therefore it can be supposed that a new GT form catalyses this reaction. It is characterized by an extraordinarily high affinity towards dt-1 with Km values ranging between 0.7 and 27 μmol/l. Springer-Verlag, 1992 Sulfotransferase nationallicence UDP-Glucuronosyltransferase nationallicence Digitoxin nationallicence Metabolism nationallicence Human liver nationallicence DHEA : dehydroepiandrosterone nationallicence dg-0 : digoxigenin nationallicence dg-1 : digoxigenin-monodigitoxoside nationallicence dt-0 : digitoxigenin nationallicence dt1 : digitoxigenin-monodigitoxoside nationallicence dt-2 : digitoxigenin-bisdigitoxoside nationallicence dt-3 : digitoxigenin-trisdigitoxoside, digitoxin nationallicence epi-dt-0 : 3-epi-digitoxigenin nationallicence GT : UDP-glucuronosyltransferase nationallicence PAPS : 3′-phosphoadenosine-5′-phosphosulfate nationallicence ST : sulfotransferase nationallicence UDPGA : UDP-glucuronic acid nationallicence Schmoldt Achim Institute for Legal Medicine, University of Hamburg, Butenfeld 34, W-2000, Hamburg 54, Federal Republic of Germany aut Blömer Ingbert Institute for Legal Medicine, University of Hamburg, Butenfeld 34, W-2000, Hamburg 54, Federal Republic of Germany aut Johannes Andrea Institute for Legal Medicine, University of Hamburg, Butenfeld 34, W-2000, Hamburg 54, Federal Republic of Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/2(1992-08-01), 226-233 0028-1298 346:2<226 1992 346 210 https://doi.org/10.1007/BF00165306 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00165306 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schmoldt Achim Institute for Legal Medicine, University of Hamburg, Butenfeld 34, W-2000, Hamburg 54, Federal Republic of Germany aut NATIONALLICENCE 700 1- Blömer Ingbert Institute for Legal Medicine, University of Hamburg, Butenfeld 34, W-2000, Hamburg 54, Federal Republic of Germany aut NATIONALLICENCE 700 1- Johannes Andrea Institute for Legal Medicine, University of Hamburg, Butenfeld 34, W-2000, Hamburg 54, Federal Republic of Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/2(1992-08-01), 226-233 0028-1298 346:2<226 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer