Inhibition of purified rat liver mitochondrial monoamine oxidase by trans-2-phenyl-cyclopropylamine

Abstract

The inhibition of purified rat liver mitochondrial rnonoarnineoxidase by transphenylcyclopropylamine was studied. Both the enzyme activity and its inhibition by tranylcypromine were optimal at pH 7.0 and I 50 value was found to be 2 × 10 − M. A short period of incubation of the enzyme with the drug caused appreciable inhibition even at very low inhibitor concentration. When the substrate and inhibitor were added simultaneously higher concentrations of inhibitor were required for producing marked inhibition. The inhibition was both competitive and irreversible and no restoration of enzyme activity occurred even after prolonged dialysis. When both the substrate and inhibitor were added simultaneously the degree of inhibition was found to decrease pro-gressively with increasing concentrations of substrate. No such protective action of the substrate could be observed when the enzyme was preincubated with the inhibitor before addition of the substrate. Deamination of various monoamines was not inhibited to the same extent by tranylcypromine. Ultraviolet absorption spectra of the purified enzyme at pH 7.0 showed a peak at 410 mμ. which disappeared leaving only a shoulder at 415 mμ in the presence of tranylcypromine.