Understanding substrate selectivity of human UDP-glucuronosyltransferases through QSAR modeling and analysis of homologous enzymes
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منابع مشابه
Characterization of the metabolism of fenretinide by human liver microsomes, cytochrome P450 enzymes and UDP-glucuronosyltransferases
BACKGROUND AND PURPOSE Fenretinide (4-HPR) is a retinoic acid analogue, currently used in clinical trials in oncology. Metabolism of 4-HPR is of particular interest due to production of the active metabolite 4'-oxo 4-HPR and the clinical challenge of obtaining consistent 4-HPR plasma concentrations in patients. Here, we assessed the enzymes involved in various 4-HPR metabolic pathways. EXPERI...
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The UGT1 complex codes for a subfamily of homologous "1A7-like" UDP-glucuronosyltransferases (UGTs), including UGT1A7 and UGT1A8. Little information is available regarding either the substrate specificities or regulation of the UGT1A7-like forms from rats. We compared the activities and tissue expression of UGT1A7 and UGT1A8, which exhibit 77% identity in their amino terminal sequence. UGT1A7 s...
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Although the liver has been considered the most important organ involved in glucuronidation, recent studies have focused on the role of the gastrointestinal tract in the glucuronidation of xenobiotics and endobiotics. Two UDP-glucuronosyltransferase (UGT) isoforms of human intestinal mucosa, which are absent in liver, have been identified by reverse transcriptase-polymerase chain reaction. mRNA...
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Mammalian UDP-glucuronosyltransferases (UGTs) catalyze the transfer of glucuronic acid from UDP-glucuronic acid to various xenobiotics and endobiotics. Since UGTs comprise rate-limiting enzymes for metabolism of various compounds, co-administration of UGT-inhibiting drugs and genetic deficiency of UGT genes can cause an increased blood concentration of these compounds. During the last few decad...
متن کاملPharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity.
The human UDP-glucuronosyltransferases (UGTs) represent a superfamily of proteins (Mackenzie et al., 1997) that are attracting much interest because of their extensive polymorphic patterns of gene and tissue specific expression (Mackenzie et al., 2000; Tukey and Strassburg, 2000). Because glucuronidation comprises a significant pathway for drug detoxification and elimination, polymorphic patter...
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ژورنال
عنوان ژورنال: Xenobiotica
سال: 2012
ISSN: 0049-8254,1366-5928
DOI: 10.3109/00498254.2012.663515