Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry

Mutations in the gene encoding UDP-glucuronosyltransferase 1A1 (UGT1A1) may reduce the glucuronidation of estradiol, bilirubin, etc. In the present study, we used a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to assay the activities of recombinant mutated UGT1A1 toward 17beta-es...

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Main Authors:	Wada, Keiko, Takeuchi, Atsuko, Saiki, Kayoko, Sutomo, Retno, Van Rostenberghe, Hans, Yusoff, Narazah Mohd, Laosombat, Vichai, Sadewa, Ahmad Hamim, A.Talib, Norlelawati, Yusoff, Surini, Lee, Myeong Jin, Ayaki, Hitoshi, Nakamura, Hajime, Matsuo, Masafumi, Nishio, Hisahide
Format:	Article
Language:	English
Published:	2006
Subjects:	R Medicine (General)
Online Access:	http://irep.iium.edu.my/12678/ http://irep.iium.edu.my/12678/ http://irep.iium.edu.my/12678/1/Wada_%2C_chromatography.pdf

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recordtype	eprints
spelling	iium-126782015-09-14T03:56:44Z http://irep.iium.edu.my/12678/ Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry Wada, Keiko Takeuchi, Atsuko Saiki, Kayoko Sutomo, Retno Van Rostenberghe, Hans Yusoff, Narazah Mohd Laosombat, Vichai Sadewa, Ahmad Hamim A.Talib, Norlelawati Yusoff, Surini Lee, Myeong Jin Ayaki, Hitoshi Nakamura, Hajime Matsuo, Masafumi Nishio, Hisahide R Medicine (General) Mutations in the gene encoding UDP-glucuronosyltransferase 1A1 (UGT1A1) may reduce the glucuronidation of estradiol, bilirubin, etc. In the present study, we used a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to assay the activities of recombinant mutated UGT1A1 toward 17beta-estradiol (E2), by determining its glucuronide (E2G) content. Direct evidence for glucuronide formation was provided by E2G-specific ion peaks. The UGT1A1 activities of G71R (exon 1), F83L (exon 1), I322V (exon 2) and G493R (exon 5) mutants were 24, 30, 18 and 0.6% of the normal UGT1A1 activity, respectively. In conclusion, our study showed that LC/MS/MS enabled accurate evaluation of the effects of mutations on recombinant UGT1A1 activity towards E2. 2006 Article PeerReviewed application/pdf en http://irep.iium.edu.my/12678/1/Wada_%2C_chromatography.pdf Wada, Keiko and Takeuchi, Atsuko and Saiki, Kayoko and Sutomo, Retno and Van Rostenberghe, Hans and Yusoff, Narazah Mohd and Laosombat, Vichai and Sadewa, Ahmad Hamim and A.Talib, Norlelawati and Yusoff, Surini and Lee, Myeong Jin and Ayaki, Hitoshi and Nakamura, Hajime and Matsuo, Masafumi and Nishio, Hisahide (2006) Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 838 (1). pp. 9-14. ISSN 1570-0232 http://www.lib.kobe-u.ac.jp/handle_kernel/90001403
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	R Medicine (General)
spellingShingle	R Medicine (General) Wada, Keiko Takeuchi, Atsuko Saiki, Kayoko Sutomo, Retno Van Rostenberghe, Hans Yusoff, Narazah Mohd Laosombat, Vichai Sadewa, Ahmad Hamim A.Talib, Norlelawati Yusoff, Surini Lee, Myeong Jin Ayaki, Hitoshi Nakamura, Hajime Matsuo, Masafumi Nishio, Hisahide Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry
description	Mutations in the gene encoding UDP-glucuronosyltransferase 1A1 (UGT1A1) may reduce the glucuronidation of estradiol, bilirubin, etc. In the present study, we used a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to assay the activities of recombinant mutated UGT1A1 toward 17beta-estradiol (E2), by determining its glucuronide (E2G) content. Direct evidence for glucuronide formation was provided by E2G-specific ion peaks. The UGT1A1 activities of G71R (exon 1), F83L (exon 1), I322V (exon 2) and G493R (exon 5) mutants were 24, 30, 18 and 0.6% of the normal UGT1A1 activity, respectively. In conclusion, our study showed that LC/MS/MS enabled accurate evaluation of the effects of mutations on recombinant UGT1A1 activity towards E2.
format	Article
author	Wada, Keiko Takeuchi, Atsuko Saiki, Kayoko Sutomo, Retno Van Rostenberghe, Hans Yusoff, Narazah Mohd Laosombat, Vichai Sadewa, Ahmad Hamim A.Talib, Norlelawati Yusoff, Surini Lee, Myeong Jin Ayaki, Hitoshi Nakamura, Hajime Matsuo, Masafumi Nishio, Hisahide
author_facet	Wada, Keiko Takeuchi, Atsuko Saiki, Kayoko Sutomo, Retno Van Rostenberghe, Hans Yusoff, Narazah Mohd Laosombat, Vichai Sadewa, Ahmad Hamim A.Talib, Norlelawati Yusoff, Surini Lee, Myeong Jin Ayaki, Hitoshi Nakamura, Hajime Matsuo, Masafumi Nishio, Hisahide
author_sort	Wada, Keiko
title	Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry
title_short	Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry
title_full	Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry
title_fullStr	Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry
title_full_unstemmed	Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry
title_sort	evaluation of mutation effects on ugt1a1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry
publishDate	2006
url	http://irep.iium.edu.my/12678/ http://irep.iium.edu.my/12678/ http://irep.iium.edu.my/12678/1/Wada_%2C_chromatography.pdf
first_indexed	2023-09-18T20:21:49Z
last_indexed	2023-09-18T20:21:49Z
_version_	1777408157006430208

Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry

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