Evidence for a digitoxin conjugating UDP-glucuronosyltransferase in the dog.
Liver microsomes of male Beagle dogs contain a form of UDP-glucuronyltransferase which is capable of conjugating digitoxin and its cleavage products digitoxigenin-bisdigitoxoside and digitoxigenin-monodigitoxoside. The highest reaction rates (Vmax 236 pmoles/mg microsomal protein min) were found for digitoxin and digitoxigenin-monodigitoxoside whereas the lowest Km was obtained for digitoxigenin-bisdigitoxoside (29 microM). Digoxin cannot be glucuronidated and digitoxigenin is glucuronidated only in traces. The result may explain the fast digitoxin elimination in dogs. Mutual induction experiments utilizing cardenolides and model substrates of UDP-glucuronyltransferase result in the conclusion that a specific form of UDP-glucuronyltransferase is responsible for glucuronidating digitoxigenin glycosides.
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism; D004073:Digitoxigenin / Q000031:analogs & derivatives / Q000378:metabolism; D004074:Digitoxin / Q000378:metabolism* / Q000493:pharmacokinetics; D004285:Dogs; D005965:Glucuronates / Q000096:biosynthesis; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009596:Nitrophenols / Q000378:metabolism; D011276:Pregnanediol / Q000378:metabolism; D013379:Substrate Specificity; D013739:Testosterone / Q000378:metabolism
D001713:Biphenyl Compounds; D005965:Glucuronates; D009596:Nitrophenols; D004073:Digitoxigenin; C038148:digitoxigenin-bis(digitoxoside); C035486:digitoxigenin monodigitoxoside; D013739:Testosterone; C019046:4-phenylphenol; D004074:Digitoxin; D014453:Glucuronosyltransferase; D011276:Pregnanediol; C024836:4-nitrophenol