N-glucuronidation catalyzed by UGT1A4 and UGT2B10 in human liver microsomes: Assay optimization and substrate identification.
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Lu D, Xie Q, Wu B
N-glucuronidation catalyzed by UGT1A4 and UGT2B10 in human liver microsomes: Assay optimization and substrate identification.
J Pharm Biomed Anal. 2017 Oct 25;145:692-703. doi: 10.1016/j.jpba.2017.07.037. Epub 2017 Aug 4.
- PubMed ID
- 28803208 [ View in PubMed]
- Abstract
N-glucuronidation is an important pathway for metabolism and disposition of tertiary amines in humans. This reaction is mainly catalyzed by the enzymes UGT1A4 and UGT2B10. However, the metabolic patterns of UGT1A4- and UGT2B10-mediated N-glucuronidation are not fully clear. In this study, we first optimized in vitro reaction conditions for N-glucuronidation by using specific substrates (i.e., trifluoperazine for UGT1A4, cotinine and amitriptyline for UGT2B10). Furthermore, we found that hepatic N-glucuronidation showed significant species differences. In addition, UGT1A4 and UGT2B10 were primarily responsible for N-glucuronidation of many tertiary amines, including asenapine, loxapine, clozapine, chlorpromazine, dothiepin, doxepin, mirtazapine, mianserin, chlorcyclizine, cyclizine, promethazine, cyclobenzaprine, imatinib, retrorsine, strychnine and brucine. In conclusion, this study provides an in vitro assay system for evaluating N-glucuronidation of amines. Also, UGT1A4- and UGT2B10-mediated N-glucuronidation might play significant roles in metabolism and detoxification of tertiary amines in humans.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Cyclobenzaprine UDP-glucuronosyltransferase 1-4 Protein Humans UnknownSubstrateDetails Cyclobenzaprine UDP-glucuronosyltransferase 2B10 Protein Humans UnknownSubstrateDetails - Drug Reactions
Reaction Details
