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

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

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Abstract

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.

Item Type: Article (Journal)
Additional Information: 4667/12678
Uncontrolled Keywords: UGT1A1; Mutation; 17beta-estradiol
Subjects: R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes: Kulliyyah of Medicine
Depositing User: Dr Norlelawati A.Talib
Date Deposited: 18 Jan 2012 07:12
Last Modified: 14 Sep 2015 03:56
URI: http://irep.iium.edu.my/id/eprint/12678

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