INHIBITION OF BOVINE LUNG SEMICARBAZIDE-SENSITIVE AMINE OXIDASE (SSAO) BY SOME HYDRAZINE DERIVATIVES

Microsomal semicarbazide-sensitive amine oxidase (SSAO) from bovine lu ng was shown to be inhibit-ed by a number of hydrazine derivatives, bu t the mechanisms of inhibition were found to differ. Hydralazine behav ed as an irreversible and partially time-dependent inhibitor with an I C50 value of 1 mu M under the conditions used. Phenylhydrazine was fou nd to be a potent irreversible inhibitor of SSAO (IC50 30 nM). Semicar bazide behaved as a specific irreversible inhibitor (active-site-direc ted irreversible inhibitor) in first forming a non-covalent enzyme-sem icarbazide complex (with a K-i value of 85 mu M), which then reacted t o give an irreversibly inhibited enzyme species in a reaction defined by the first-order rate constant k(2) = 0.065 min(-1). Phenelzine beha ved as a reversible inhibitor, but dialysis at 37 degrees C was found to be necessary to obtain full recovery of enzyme activity. The depend ence of inhibition on phenelzine concentration was complex and consist ent with multiple binding sites for this inhibitor. This diversity in the action of a family of compounds with the same functional group mus t be taken into account in attempts to design more specific inhibitors of this enzyme.