Studies on Catecholamine Biosynthesis.IV. Inhibition of Dopamine β-Hydroxylase by Thiourea Derivatives

Abstract

Some properties of dopamine β-hydroxylase (DβH) in the homogenate of bovine adrenal medulla and inhibitory effects of thiourea derivatives on DβH were examined. Enzymic formation of norsynephrine from tyramine in the homogenate of the adrenal medulla was linear with respect to time (up to 30 min) and protein concentration (up to 160 μg). By typical Lineweaver-Burk plots, Km value was calculated to be 4×10^-3M. Among the compounds tested, N-phenyl-N'-[3-(4H-1, 2, 4-triazolyl)]thiourea and N-n-butyl-N'-[3-(4H-1, 2, 4-triazolyl)]thiourea were effective inhibitors, and inhibition by the latter was non-competitive with substrate tyramine. Structure-activity relationship between thiourea derivatives and the inhibitory effect on DβH was discussed.