Nicotine and its primary oxidative metabolites are metabolized in part by glucuronidation. Genetic variation in UGT isoenzymes that catalyze glucuronidation activity suggests that variation in glucuronidation rate is in part genetically determined. The relative contribution of genetic and environmental sources to individual differences in the rate of glucuronidation of nicotine, cotinine, and t...

Previous results demonstrating homotropic activation of human UDP-glucuronosyltransferase (UGT) 1A1-catalyzed estradiol-3-glucuronidation led us to investigate the effects of 16 compounds on estradiol glucuronidation by human liver microsomes (HLM). In confirmation of previous work using alamethicin-treated HLM pooled from four livers, UGT1A1-catalyzed estradiol-3-glucuronidation demonstrated h...

Chloramphenicol (CP), a broad spectrum antibiotic, is eliminated in humans by glucuronidation. The primary UGT enzymes responsible for CP O-glucuronidation remain unidentified. We have previously identified the 3-O-CP (major) and 1-O-CP (minor) glucuronides by beta-glucuronidase hydrolysis, liquid chromatography-tandem mass spectrometry, and 1D/2D H NMR. Reaction phenotyping for the glucuronida...

Glucuronidation is an important pathway in the elimination of salvianolic acid A (Sal A); however the mechanism of UDP-glucuronosyltransferases (UGTs) in this process remains to be investigated. In this study, the kinetics of Sal A glucuronidation by pooled human liver microsomes (HLMs), pooled human intestinal microsomes (HIMs) and 12 recombinant UGT isozymes were investigated. The glucuronida...

Two human UDP-glucuronosyltransferases (UGTs), UGT2B7 and UGT1A1, catalyze the glucuronidation of many endo- and xenobiotics. Although UGT1A1 uniquely catalyzes the glucuronidation of the endobiotic, bilirubin, and UGT2B7 uniquely catalyzes the glucuronidation of morphine to both the 3-0 glucuronide and the 6-0 glucuronide, both catalyze the glucuronidation of the mixed opioid agonist/antagonis...

We have examined the glucuronidation of psilocin, a hallucinogenic indole alkaloid, by the 19 recombinant human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A, and 2B. The glucuronidation of 4-hydroxyindole, a related indole that lacks the N,N-dimethylaminoethyl side chain, was studied as well. UGT1A10 exhibited the highest psilocin glucuronidation activity, whereas the activities of...

Glucuronidation is an important pathway in the metabolism of protocatechuic aldehyde (3,4-dihydroxybenzaldehyde, PAL). However, the metabolites and primary UDP-glucuronosyltransferase (UGT) isozymes responsible for PAL glucuronidation remain to be determined in human. Here, we characterized PAL glucuronidation by human liver microsomes (HLMs), human intestine microsomes (HIMs), and 12 recombina...

The in vitro glucuronidation of a range of structurally diverse chemicals has been studied in hepatic and renal microsomes from human donors and the beagle dog. These studies were undertaken to improve on the limited knowledge of glucuronidation by the dog and to assess its suitability as a model species for pharmacokinetic studies. In general, the compounds studied were glucuronidated severalf...

Uridine diphosphate glucuronosyltransferases (UGTs) catalyze the glucuronidation of a wide range of xenobiotics and endogenous substrates. However, there is a lack of information concerning the response of human UGTs to inducers, and this observation prompted the current investigation. The glucuronidation of estradiol (3- and 17-positions), naphthol, propofol, and morphine (3- and 6-positions) ...

Opioids are important drugs used as analgesics, antitussives, antidiarrheals, and in the therapy of myocardial infarctions, and as antagonists of opioid intoxication. The glucuronidation of these compounds, catalyzed by UDP-glucuronosyltransferases (UGTs), is well known to be a primary step in their metabolism to hydrophilic products and in their ultimate excretion. The present study was design...