Kinetics of the Reversible Tight-Binding Inhibition of Pig Liver Catechol-O-Methyltransferase by [2-(3,4-Dihydroxy-2-Nitrophenyl) Vinyl] Phenyl Ketone

Abstract

The inactivation of partially purified pig liver catechol-O-methyltransferase (COMT) by [2-(3,4-dihydroxy-2-nitrophenyl)vinyl]phenylketone has been studied. The results demonstrated that COMT is inhibited in a reversible tight-binding fashion with an apparent K_i of 0.2 μM. IC₅₀ values were determined at different concentrations of both substrates of the enzymatic reaction, pyrocatechol and S-adenosyl-L-methionine (AdoMet). The plot of 1C₅₀ versus pyrocatechol concentration gave a straight line, suggesting competitive inhibition. However the nitrocatechol derivative showed an uncompetitive inhibition pattern when measured as a function of AdoMet concentration.

Key Words: :

• COMT
• tight-binding inhibitors
• catechol-O-methyltransferase