Various inhibitors of copper amine oxidases (CAOs) have been studied.  Escherichia coli AO (ECAO) can be completely and irreversibly inactivated by phenelzine, isoniazid, tranycypromine and 2-hydrazinopyridine (hydrazine derivatives) that form a mimic enzyme-substrate Schiff base complex.5  The figure below gives the inhibition mechanism for lentil AO.  CAOs can be inhibited by short chain amines, and 2-haloethylamines behave like suicide substrates.  The conclusions of the study by Rosaria Medda et al. were that all 2-substituted ethylamines appear to inhibit using the same mechanism, while a different mechanism works for all 3-substituted propylamines.  They also concluded that in every case, reaction of product aldehyde with enzyme caused the inhibition.   2-haloethylamines' inactivation of CAOs is termed a "killer product mechanism."6  The results of the experiments done by Benjamin Schwartz et al. showed that the mutation of the highly conserved asparagine 404 residue near the redox cofactor topa quinone to an alanine in HPAO resulted in inactive product Schiff base complex when the substrate during incubation was methylamine. Mechanism of inactivation of lentil amine oxidase (LSAO) by 2-Cl-ethylamine, 1,2-diaminoethane, and 2-Br-ethylamine.  The reaction with the aldehyde in the first step is believed to be reversible.  Ring closure and release of the substituent is the next irreversible step and results in the formation of a stable six-membered ring.  Ammonia is eliminated at C-2.6 Figure from Rosaria Medda et al.

Dawn Schroeder                             Chemistry 406, 1998