Inhibition of dopamine-beta-hydroxylase by alternative electron donors

The alternative electron donors ferrocyanide and hydroquinone have been shown to also act as inhibitors of dopamine-beta-hydroxylase (3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1). Hydroquine shows uncompetitive inhibition with respect to ascorbate and competitive inhibition with respect to tyramine. Ferrocyanide shows uncompetitive inhibition with respect to ascorbate and mixed type inhibition with respect to tyramine. Inhibition by ferrocyanide at concentrations at or above 2.5 . 10(-5) M was prevented by 2.5 . 10(-6) M cupric ion. These results indicate that the inhibitory action of these alternative electron donors is due to their interaction with a reduced enzyme species. The potency of inhibition of dopamine-beta-hydroxylase by both ferrocyanide and hydroquinone is dependent on the degree of protonation of a group in the enzyme having a pKa of 5.3.