title: Inhibition of rat liver and duodenum soluble catechol-O-methyltransferase by a tight-binding inhibitor OR-462.
abstract: The inhibition kinetics of rat liver and duodenum soluble catechol-O-methyltransferase (COMT) with a disubstituted catechol OR-462 was studied. After preincubation of the enzyme and inhibitor in the presence of magnesium and S-adenyosylmethionine, an inhibition about thirty times greater than that without preincubation was observed. Reversible tight-binding inhibition was demonstrated with Ki values of 0.7 nM and 1.0 nM for liver and duodenum enzyme, respectively. Km values of 53.4 microM and 56.9 microM for substrate 3,4-dihydroxybenzoic acid and 23.0 microM and 17.5 microM for S-adenosylmethionine were calculated for liver and duodenum enzyme, respectively. A catalytic number of 24/min for liver soluble COMT was calculated.
authors.affiliation: Orion Pharmaceutica, Research Center, Espoo, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Schultz
authors.forename: E
authors.initials: E
authors.lastname: Nissinen
mesh_terms: D000818:Animals; D002384:Catalysis; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D004386:Duodenum / Q000201:enzymology*; D062385:Hydroxybenzoates / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D010422:Pentanones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000494:pharmacology
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D062385:Hydroxybenzoates; D007659:Ketones; D010422:Pentanones; C009091:protocatechuic acid; D012436:S-Adenosylmethionine; C057364:nitecapone; D008274:Magnesium