Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1216588 | Journal of Chromatography B | 2006 | 6 Pages |
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 17β-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.
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Keiko Wada, Atsuko Takeuchi, Kayoko Saiki, Retno Sutomo, Hans Van Rostenberghe, Narazah Mohd Yusoff, Vichai Laosombat, Ahmad Hamim Sadewa, Norlelawati Abdul Talib, Surini Yusoff, Myeong Jin Lee, Hitoshi Ayaki, Hajime Nakamura, Masafumi Matsuo,