کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1991979 | 1541061 | 2009 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of human catechol-O-methyltransferase (COMT)-mediated O-methylation of catechol estrogens by major polyphenolic components present in coffee
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کلمات کلیدی
Catechol-O-methyltransferase4-OH-E22-OH-E2AdoHcyAdoMetCOMTCAPES-adenosyl-l-homocysteine2-hydroxyestradiol - 2-هیدروکسی استرادیول4-Hydroxyestradiol - 4-هیدروکسی استرادیولS-adenosyl-L-methionine - S-adenosyl-L-metionineCatechol estrogens - استروژن کایتوکلcaffeic acid phenethyl ester - اسید کافئیک اسید فین الی استرPlacenta - جفت Estrogen metabolism - متابولیسم استروژنComputational modeling - مدل سازی محاسباتیEnzyme inhibition - مهار آنزیمCatechol-O-methyltransferase (COMT) - کاتچول O-متیل ترانسفراز (COMT)Liver - کبد
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
In the present study, we investigated the inhibitory effect of three catechol-containing coffee polyphenols, chlorogenic acid, caffeic acid and caffeic acid phenethyl ester (CAPE), 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. CAPE had a comparable effect as caffeic acid for inhibiting the O-methylation of 2-OH-E2, but it exerted 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 113, Issues 1â2, January 2009, Pages 65-74
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 113, Issues 1â2, January 2009, Pages 65-74
نویسندگان
Bao Ting Zhu, Pan Wang, Mime Nagai, Yujing Wen, Hyoung-Woo Bai,