title: Hydroxysteroid sulfotransferase and a specific UDP-glucuronosyltransferase are involved in the metabolism of digitoxin in man.
abstract: 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 mumol/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 mumol/l.
authors.affiliation: Institute for Legal Medicine, University of Hamburg, Federal Republic of Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schmoldt
authors.forename: I
authors.initials: I
authors.lastname: Blömer
authors.forename: A
authors.initials: A
authors.lastname: Johannes
mesh_terms: D001667:Binding, Competitive; D003600:Cytosol / Q000201:enzymology; D004073:Digitoxigenin / Q000031:analogs & derivatives / Q000378:metabolism; D004074:Digitoxin / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D013379:Substrate Specificity; D015238:Sulfotransferases; D013455:Sulfur / Q000378:metabolism; D013466:Sulfurtransferases / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D005965:Glucuronates; D004073:Digitoxigenin; D013455:Sulfur; D004074:Digitoxin; D014453:Glucuronosyltransferase; D013466:Sulfurtransferases; D015238:Sulfotransferases; C028152:alcohol sulfotransferase