کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5137790 | 1494590 | 2017 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
N-glucuronidation catalyzed by UGT1A4 and UGT2B10 in human liver microsomes: Assay optimization and substrate identification
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کلمات کلیدی
UGTUPLCqTOFHLMNNALUDPGAUGT1A44-(methylnitrosamino)-1-(3-pyridyl)-1-butanol - 4- (methylnitrosamino) -1- (3-pyridyl) -1-butanolUDP-glucuronosyltransferase - UDP-گلوکورونوسیل ترانسفرازTertiary amines - آمینهای ترتیادیuridine diphosphoglucuronic acid - اسید یدید دی فسفوگلوکورونیکSpecies differences - تفاوت گونه هاquadrupole time-of-flight - زمان پرواز چهار روزهMass spectroscopy - طیف سنجی جرمیHuman Liver Microsomes - میکروسومهای کبدی انسانیultra performance liquid chromatography - کروماتوگرافی مایع با عملکرد فوق العاده
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 145, 25 October 2017, Pages 692-703
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 145, 25 October 2017, Pages 692-703
نویسندگان
Danyi Lu, Qian Xie, Baojian Wu,