Regulation profile of phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs) components towards UDP-glucuronosyltransferases (UGTs) isoforms
- 15 September 2014
- journal article
- research article
- Published by Informa UK Limited in Xenobiotica
- Vol. 45 (3), 197-206
- https://doi.org/10.3109/00498254.2014.966174
Abstract
1. Endogenous compounds have been reported to be the regulators of UDP-glucuronosyltransferases (UGTs) isoforms. This study aims to investigate the regulatory effects of the activity of UGT isoforms by two important lipid components phosphatidylcholine (PC) and lysophosphatidylcholines (LPC) using in vitro incubation system. 2. UGTs supersomes-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as the probe reaction to evaluate the inhibition of compounds towards UGT isoforms except UGT1A4, and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation reaction was utilized to phenotype the activity of UGT1A4. 3. About 50 μM of LPC15:0, LPC16:0, LPC17:0, LPC18:0, LPC18:1 and PC16:0, 2:0 exhibited inhibition towards more than 90% activity of UGT isoforms, and other LPC and PC components showed negligible inhibitory potential towards all the UGT isoforms. UGT1A6 and UGT1A8 were identified to be the most sensitive UGT isoforms susceptible for the inhibition by LPC15:0, LPC16:0, LPC17:0, LPC18:0, LPC18:1 and PC16:0, 2:0, indicating the strong influence of these LPC and PC components towards UGT1A6 and UGT1A8-catalyzed metabolic reaction when the concentrations of these components increased.Keywords
This publication has 17 references indexed in Scilit:
- Effect of UDP-glucuronosyltransferase 1A8 polymorphism on raloxifene glucuronidationEuropean Journal of Pharmaceutical Sciences, 2013
- Structure–inhibition relationship of ginsenosides towards UDP-glucuronosyltransferases (UGTs)Toxicology and Applied Pharmacology, 2013
- Metabolomic analysis and identification of a role for the orphan human cytochrome P450 2W1 in selective oxidation of lysophospholipidsJournal of Lipid Research, 2012
- ATP Serves as an Endogenous Inhibitor of UDP-Glucuronosyltransferase (UGT): A New Insight into the Latency of UGTPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2012
- Lysophosphatidylcholine as an effector of fatty acid-induced insulin resistanceJournal of Lipid Research, 2011
- UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenibCancer Chemotherapy and Pharmacology, 2009
- SELECTIVITY OF SUBSTRATE (TRIFLUOPERAZINE) AND INHIBITOR (AMITRIPTYLINE, ANDROSTERONE, CANRENOIC ACID, HECOGENIN, PHENYLBUTAZONE, QUINIDINE, QUININE, AND SULFINPYRAZONE) “PROBES” FOR HUMAN UDP-GLUCURONOSYLTRANSFERASESDrug Metabolism and Disposition, 2005
- The emerging field of lipidomicsNature Reviews Drug Discovery, 2005
- UDP‐Glucuronosyltransferase 1A6: Structural, Functional, and Regulatory AspectsMethods in enzymology, 2005
- Properties of human hepatic UDP-glucuronosyltransferases. Relationship to other inducible enzymes in patients with cholestasisEuropean Journal of Clinical Pharmacology, 1987