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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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Bibliographic Details
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/12678/1/Wada_%2C_chromatography.pdf
http://irep.iium.edu.my/12678/
http://www.lib.kobe-u.ac.jp/handle_kernel/90001403
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Summary: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.

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