Inhibition of human catechol-O-methyltransferase (COMT)-mediated O-methylation of catechol estrogens by major polyphenolic components present in coffee.
Inhibition of human catechol-O-methyltransferase (COMT)-mediated O-methylation of catechol estrogens by major polyphenolic components present in coffee.
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DOI：
10.1016/j.jsbmb.2008.11.011
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发表时间：
2009-01
影响因子：
4.1
通讯作者：
Bai, Hyoung-Woo
中科院分区：
文献类型：
--
作者：
Zhu, Bao Ting;Wang, Pan;Nagai, Mime;Wen, Yujing;Bai, Hyoung-Woo
关键词：
In the present study, we investigated the inhibitory effect of three catechol-containing coffee polyphenols, chlorogenic acid, caffeic acid and caffeic acid phenethyl ester, on the O-methylation of 2- and 4-hydroxyestradiol (2-OH-E2 and 4-OH-E2, respectively) catalyzed by the cytosolic catechol-O-methyltransferase (COMT) isolated from human liver and placenta. When human liver COMT was used as the enzyme, chlorogenic acid and caffeic acid each inhibited the O-methylation of 2-OH-E2 in a concentration-dependent manner, with IC50 values of 1.3–1.4 and 6.3–12.5 μM, respectively, and they also inhibited the O-methylation of 4-OH-E2, with IC50 values of 0.7–0.8 and 1.3–3.1 μM, respectively. Similar inhibition pattern was seen with human placental COMT preparation. Caffeic acid phenethyl ester had a comparable effect as caffeic acid for inhibiting the O-methylation of 2-OH-E2, but it had a weaker inhibition of the O-methylation of 4-OH-E2. Enzyme kinetic analyses showed that chlorogenic acid and caffeic acid inhibited the human liver and placental COMT-mediated O-methylation of catechol estrogens with a mixed mechanism of inhibition (competitive plus noncompetitive). Computational molecular modeling analysis showed that chlorogenic acid and caffeic acid can bind to human soluble COMT at the active site in a similar manner as the catechol estrogen substrates. Moreover, the binding energy values of these two coffee polyphenols are lower than that of catechol estrogens, which means that coffee polyphenols have higher binding affinity for the enzyme than the natural substrates. This computational finding agreed perfectly with our biochemical data.
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影响因子：
3.8
作者：
Wen, WQ;Cai, QY;Zheng, W
通讯作者：
Zheng, W
影响因子：
6.1
作者：
Azuma, K;Ippoushi, K;Terao, J
通讯作者：
Terao, J
影响因子：
3.6
作者：
Lautala, P;Ulmanen, I;Taskinen, J
通讯作者：
Taskinen, J
影响因子：
1.8
作者：
Zhu, B. T.;Shim, J. -Y.;Bai, H. -W.
通讯作者：
Bai, H. -W.
影响因子：
3.9
作者：
Nagai, M;Conney, AH;Zhu, BT
通讯作者：
Zhu, BT