Human uridine-5'-diphosphoglucuronosyltransferases (UGTs) are the major phase II metabolizing enzymes. In the present study, five human UGTs (UGT1A1, 1A4, 1A6, 2B7, and 2B10) were individually expressed and used to examine the inhibition IC(50) values of 20 selective substrates and inhibitors of major cytochromes P450 (CYPs). The inhibition kinetics of UGT1A1 was also analyzed. The results show...

Uridine glucuronosyltransferase (UGT) gene polymorphisms have been linked to irinotecan toxicity. Our purpose was to study the association between UGT1A1*28, UGT1A7*2, and UGT1A7*3 polymorphisms and irinotecan toxicity in Greek patients receiving low-dose weekly irinotecan. Blood samples were collected for 46 patients. DNA was extracted and UGT1A1 promoter and UGT1A7 exon 1 genotyping was carri...

Human uridine 5'-diphosphate-glucuronosyltransferases play a critical role in detoxification by conjugating bilirubin with glucoronic acid. Impaired or reduced enzymatic activity causes a spectrum of clinical disorders such as Crigler-Najjar syndrome type I (CN1), Crigler-Najjar syndrome type II, and Gilbert's syndrome. CN1 is a severe form of unconjugated hyperbilirubinemia caused by homozygou...

objective: jaundice with indirect hyperbilirubinemia is one of the most common neonatal problems that occur in 60% of term and 80% of preterm neonates but the causes are mostly unknown. it is suggested that race plays an important role in the prevalence of hyperbilirubinemia. it is a common problem in iran that worries both parents and pediatricians. it has been found that a mutation in the ugt...

Human UDP-glucuronosyltransferase (UGT) 1A1 catalyzes the metabolism of numerous clinically and pharmacologically important compounds such as bilirubin and SN-38. UGT1A1 is predominantly expressed in the liver and intestine, but not in the kidney. The purpose of this study was to uncover the mechanism of the tissue-specific expression of UGT1A1, focusing on its epigenetic regulation. Bisulfite ...

Glucoraphanin in Brassica vegetables breaks down to either sulforaphane or sulforaphane nitrile depending on the conditions, and sulforaphane can be further conjugated with glutathione. Using a high-throughput microtitre plate assay and TaqMan real time quantitative RT-PCR to measure mRNA, we show that sulforaphane and its glutathione conjugate, but not the nitrile, increased significantly (P <...

BACKGROUND Combinations of genetic polymorphisms in biotransformation enzymes might modify the individual risk for head and neck cancer. METHODS Blood from 432 patients with head and neck cancer and 437 controls was investigated for genetic polymorphisms in 9 different phase I and II biotransformation enzymes. Analysis of the risk-modifying effect was performed according to predicted enzyme a...

Coimmunoprecipitation was used to investigate protein-protein interactions between several UDP-glucuronosyltransferase (UGT) isoforms and cytochrome P450 3A4. Solubilized human liver microsomes were incubated with specific antibodies to UGT2B7, UGT1A6, UGT1A1, and CYP3A4, and the immunoprecipitates were run on SDS-polyacrylamide gel electrophoresis. Western blots showed that UGT2B7, UGT1A6, UGT...

7-Ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of antitumor agent irinotecan (CPT-11), is conjugated and detoxified to SN-38-glucuronide by UDP-glucuronosyltransferase (UGT) 1A1. Genetic polymorphisms in UGT1A1 are thought to contribute to severe diarrhea and/or leukopenia caused by CPT-11. In this regard, it has been reported that polymorphisms in the promoter region could affect...

Hyperbilirubinemia is the most common problem encountered in terms newborns which is mainly caused by abnormal liver function, hemolysis or genetic defect. Uncongugated bilirubin is produced mainly by the turnover of erythrocytes, after that it is transported by organic anion transporter polypeptide (OATP) to the liver, where uncongugated bilirubin is conjugated by uridine diphosphoglucuronate ...