Inhibition of dopamine-beta-hydroxylase, A copper enzyme, by bleomycin

Bleomycin was found to be one of the most potent inhibitors of dopamine-beta-hydroxylase. Bleomycin-A2 at 8 X 10(-8) M inhibited the enzyme activity by 50%. Kinetic studies showed that the inhibition by bleomycin-A2 was of the competitive type with both the substrate and the cofactor, ascorbate, and was not affected by fumarate, a stimulator for the enzyme. The inhibition mechanism is possibly due to chelating action of bleomycin toward the copper atom at the active site of the enzyme together with some other kinds of binding, for the addition of the cupric ions or extensive dialysis completely reversed the inhibition and bleomycin Cu(II)-complex did not inhibit the enzyme.