期刊
MOLECULAR PHARMACEUTICS
卷 6, 期 5, 页码 1466-1482出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp8002557
关键词
UGT; glucuronidation; fingerprinting; profile; genistein; isoflavones
资金
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM070737] Funding Source: NIH RePORTER
- NIGMS NIH HHS [R01 GM070737, R01 GM070737-01A2, GM-070737] Funding Source: Medline
We characterized the isoform specific glucuronidation of six isoflavones, genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, using 12 expressed human UGTs and human intestinal and liver microsomes. The results indicated that these isoflavones are metabolized most rapidly at three different concentrations by one of these four UGT isoforms: UGT1A1, UGT1A8, UGT1A9 and UGT1A10. Furthermore, glycitein was usually metabolized the fastest whereas prunetin the slowest. Using the rates of metabolism by 12 UGT isoforms as a means to establish the metabolic fingerprint, we found that each isoflavone had distinctive concentration-dependent patterns. Determination of kinetic parameters of glucuronidation using genistein and prunetin indicated that the distinct concentration-dependent metabolic patterns were the result of differences in K-m and V-max values. We then measured how well metabolic fingerprinting predicted metabolism of these isoflavones by human intestinal and liver microsomes. We found that the prediction was rather successful for five isoflavones in the liver microsomes, but not successful in the intestinal microsomes. We propose that a newly discovered UGT3A1 isoform capable of metabolizing phenols and estrogens might be responsible for the metabolism of isoflavones such as formononetin in humans. In conclusion, the first systematic study of metabolic fingerprinting of six common isoflavones showed that each isoflavone has UGT isoform-specific metabolic patterns that are concentration-dependent and predictive of metabolism of the isoflavones in liver microsomes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据