Hepatic microsomal UDP-glucuronosyltransferases towards androsterone and testosterone were purified by chromatofocusing and UDP-hexanolamine affinity chromatograpy in Wistar rats which had genetic deficiency of androsterone UDP-glucuronosyltransferase activity. In rats with the high-activity phenotype, androsterone (the 3-hydroxy androgen) UDP-glucuronosyltransferase was eluted at about pH 7.4 ...

to determine the association between polymorphism of ugt1a1 gene and idiopathic hyperbilirubinemia in iranian neonates. fifty neonates with idiopathic hyperbilirubinemia and serum total bilirubin (stb) more that 15mg/dl and 50 neonates with idiopathic hyperbilirubinemia and serum total bilirubin (stb) less than 15mg/dl enrolled in this study. thymine-adenine (ta)  repeats in the promoter region...

Tranilast is an oral antiallergic agent widely used in Japan. Recently, in Western populations, hyperbilirubinemia induced by tranilast was suspected during clinical trials. Tranilast has been reported to be mainly metabolized to a glucuronide and a phase I metabolite, 4-demethyltranilast (N-3). In the present study, we investigated the in vitro metabolism of tranilast in human liver and jejunu...

The effects of cholesterol on the activity and thermal properties of a pure, delipidated isoform of UDP-glucuronosyltransferase were examined after incorporation of enzyme into unilamellar bilayers of distearoylphosphatidylcholine (DSPC) or dioleoylphosphatidylcholine (DOPC). Cholesterol, in bilayers of DSPC, decreased enzyme activity and lowered the temperature (from 37 to 30 degrees C) for a ...

Microsomal preparations from livers of Sprague-Dawley rats catalyze the glucuronidation of 3 alpha-hydroxy-5 beta-H (3 alpha, 5 beta) short-chain bile acids (C20-C23), predominantly at the hydroxyl group, while the glucuronidation of 3 beta, 5 beta short-chain bile acids occurs exclusively at the carboxyl group. A similar pattern of conjugation was also observed in Wistar rats having normal lev...

Raltegravir is an HIV integrase inhibitor that is metabolized through glucuronidation by uridine diphosphate glucuronosyltransferase 1A1, and its use is anticipated in combination with atazanavir (a uridine diphosphate glucuronosyltransferase 1A1 inhibitor). Two pharmacokinetic studies of healthy subjects assessed the effect of multiple-dose atazanavir or ritonavir-boosted atazanavir on raltegr...

Troglitazone glucuronidation in human liver and intestine microsomes and recombinant UDP-glucuronosyltransferases (UGTs) were thoroughly characterized. All recombinant UGT isoforms in baculovirus-infected insect cells (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B15) exhibited troglitazone glucuronosyltransferase activity. Especially UGT1A8 and UGT1A10, whic...

A rat kidney phenol UDP-glucuronosyltransferase cDNA was used to isolate a human liver phenol UDP-glucuronosyltransferase cDNA by screening of a human liver cDNA library in the expression vector lambda gt11. The 2.4-kilobase cDNA contained an open reading frame of 1593 base pairs coding for a protein of 531 residues. The human liver cDNA was subcloned into the vector pKCRH2. Transfection of thi...

Trans-3'-hydroxycotinine is a major metabolite of nicotine in humans and is mainly excreted as O-glucuronide in smoker's urine. Incubation of human liver microsomes with UDP-glucuronic acid produces not only trans-3'-hydroxycotinine O-glucuronide but also N-glucuronide. The formation of N-glucuronide exceeds the formation of O-glucuronide in most human liver microsomes, although N-glucuronide h...

Glucuronidation of thyroxine is a major metabolic pathway facilitating its excretion. In this study, we characterized the glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes, and identified human UDP-glucuronosyltransferase (UGT) isoforms involved in the activity. Human jejunum microsomes showed a lower K(m) value (24.2 microM) than human liver (85.9 microM) and kidney (...