Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol.
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Ebner T, Remmel RP, Burchell B
Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol.
Mol Pharmacol. 1993 Apr;43(4):649-54.
- PubMed ID
- 8474433 [ View in PubMed]
- Abstract
The synthetic estrogen ethinylestradiol is extensively eliminated as glucuronide metabolites in humans, but the UDP-glucuronosyltransferases (UGTs) catalyzing this reaction have not been identified. Therefore, ethinylestradiol was tested as a substrate for cloned human UGTs stably expressed in V79 cell lines. Two cloned expressed human enzymes, a bilirubin UGT and a phenol UGT, were observed to catalyze the glucuronidation of ethinylestradiol. High performance liquid chromatographic analysis of the products formed revealed that the expressed bilirubin UGT specifically produced ethinylestradiol-3-glucuronide. In human liver microsomes the ratio of 3-glucuronide/17-glucuronide was 97:3. Subsequent study of the cloned expressed enzymes and human liver microsomes from Crigler-Najjar patients by kinetic analysis and by substrate inhibition strongly indicated that a human liver bilirubin UGT was largely responsible for glucuronidation of ethinylestradiol. These results may provide an explanation for jaundice caused by ethinylestradiol in certain susceptible individuals.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Estradiol UDP-glucuronosyltransferases (UGTs) (Protein Group) Protein group Humans UnknownSubstrateInducerDetails Ethinylestradiol UDP-glucuronosyltransferase 1-1 Protein Humans NoSubstrateInducerDetails Ethinylestradiol UDP-glucuronosyltransferase 1-4 Protein Humans UnknownSubstrateDetails Ethinylestradiol UDP-glucuronosyltransferase 1-9 Protein Humans UnknownSubstrateDetails - Drug Reactions
Reaction Details
