Regular ArticleProtein-Protein Interactions between Rat Hepatic Cytochromes P450 (P450s) and UDP-Glucuronosyltransferases (UGTs): Evidence for the Functionally Active UGT in P450-UGT Complex
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2019, Pharmacology and TherapeuticsCitation Excerpt :Using affinity chromatography with a CYP1A1-conjugated Sepharose 4B column, Taura and colleagues observed the co-elution of multiple UGT isoforms (although the identity of these isoforms was unknown), from rat liver microsomes (Taura et al., 2000). Similarly, co-immunoprecipitation studies with rat liver microsomes detected UGT proteins following immunoprecipitation with specific antibodies towards CYP3A2, CYP2B2, CYP2C11/13 and CYP1A2 (Ishii et al., 2007). Importantly, all co-precipitated rat UGT proteins were active exhibiting activity toward 4-MU.
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2018, Comprehensive Toxicology: Third EditionUnderlying mechanism of drug-drug interaction between pioglitazone and gemfibrozil: Gemfibrozil acyl-glucuronide is a mechanism-based inhibitor of CYP2C8
2015, Drug Metabolism and PharmacokineticsCitation Excerpt :Although the majority of CYPs and UGTs are localized on the cytoplasmic and the luminal side of the endoplasmic reticulum (ER) membrane, respectively, certain metabolites produced by CYPs are subsequently metabolized by UGTs [7,8]. The underlying mechanism has not been fully understood, but protein interactions between CYP and UGT and/or formation of metabolosome, which is a functional unit of metabolism consisting of multiple metabolism-related proteins, might contribute to the sequential metabolism across the ER membrane [9–13]. Drug–drug interactions, which are frequently related to inhibition or induction of drug-metabolizing enzymes, can result in an increase or decrease of drug concentrations in blood.
Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia
2015, Toxicology and Applied PharmacologyCitation Excerpt :Efforts have been made to identify ER membrane transporters that are responsible for the transport of bilirubin and its glucuronides across the ER membrane (Fujiwara and Itoh, 2014a, 2014b); however, such transporters have not been characterized to date. Protein interactions between UGT-UGT and -cytochrome P450 (CYP) might be involved in the transport of the substances across the ER membrane (Fujiwara et al., 2007a, 2007b, 2010a; Nakajima et al., 2007; Operaña and Tukey, 2007; Finel and Kurkela, 2008; Ishii et al., 2007). Following bilirubin metabolism in liver cells, its glucuronides are transported out of these cells through the apical surface of the hepatocytes into the bile ducts by the multidrug resistance protein 2 (MRP2/ABCC2)(Fig. 1), leading to their movement through the GI tract where they eventually come into contact with microbes in the large intestine (Keppler et al., 1997; Kamisako et al., 2000).
Extensive protein-protein interactions involving UDPGLUCURONOSYLTRANSFERASe (UGT) 2B7 in human liver microsomes
2014, Drug Metabolism and Pharmacokinetics
This work was supported in part by a Grant-in-Aid for Scientific Research (C) (Research No. 19590147, recipient YI) from the Japan Society for the Promotion of Science. Presented in part at the 125th Annual Meetings of the Pharmaceutical Society of Japan (Tokyo, Japan, March 2005) (Abstract).