title: O-methylation of catechol estrogens by human placental catechol-o-methyltransferase: interindividual differences in sensitivity to heat inactivation and to inhibition by dietary polyphenols.
abstract: The human catechol-O-methyltransferase (COMT) is a polymorphic enzyme that catalyzes the O-methylation of catechol estrogens. Recent animal studies showed that placental COMT is involved in the development of placentas and embryos, probably via the formation of 2-methoxyestradiol. In this study, we analyzed a total of 36 human term placentas to determine their cytosolic COMT activity for the O-methylation of catechol estrogens as well as their sensitivity to inhibition by heat and dietary compounds. Large variations (up to 4-fold) in the COMT activity for the formation of methoxyestrogens were noted with different human placental samples. The cytosolic COMTs in different human placentas also displayed considerable differences in their sensitivity to heat inactivation. This differential sensitivity was not associated with the overall catalytic activity for the O-methylation of catechol estrogen substrates. It was observed that there was a positive correlation (r = 0.760) between the sensitivity of the human placental COMT to heat inactivation and its sensitivity to inhibition by (-)-epigallocatechin-3-gallate (a well known tea polyphenol with COMT-inhibiting activity) but an inverse correlation (r = 0.544) between heat inactivation and inhibition by quercetin (another dietary COMT inhibitor). The differences in inhibition by these two dietary compounds are due to different mechanisms of COMT inhibition involved.
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Bao Ting
authors.initials: BT
authors.lastname: Zhu
authors.forename: Karen Y
authors.initials: KY
authors.lastname: Wu
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: May Xiaoxin
authors.initials: MX
authors.lastname: Cai
authors.forename: Allan H
authors.initials: AH
authors.lastname: Conney
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D065098:Catechol O-Methyltransferase Inhibitors; D003600:Cytosol / Q000201:enzymology; D004032:Diet; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D002393:Estrogens, Catechol / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D008745:Methylation; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology*; D059808:Polyphenols; D011247:Pregnancy
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D002393:Estrogens, Catechol; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D002394:Catechol O-Methyltransferase