INHIBITION OF COPPER AMINE OXIDASE BY HALOAMINES - A KILLER PRODUCT MECHANISM

The observation that the alkylamines 2-Br-ethylamine and 2-Cl-ethylami ne and 1,2-diaminoethane, the shortest diamine, are irreversible inhib itors of several copper amine oxidases led to the investigation of the mechanism by which these compounds react with the highly active amine oxidase from lentil seedlings. 1,2-Diaminoethane, 2-Br-ethylamine, an d 2-Cl-ethylamine were found to be both poor substrates and irreversib le inhibitors of lentil amine oxidase; inactivation took place in both the presence and absence of oxygen. All three compounds strongly affe cted the spectrum of the enzyme, leading to the formation of a stable band at 336 nm both in anaerobiosis and in aerobiosis, consistent with an interaction with the enzyme cofactor 6-hydroxydopa. On the contrar y, the coil-responding propylamine compounds 1,3-diaminopropane, 3-Br- propylamine, and 3-Cl-propylamine were reversible inhibitors of lentil amine oxidase. Inhibition was shown to be due to the aldehyde oxidati on products rather than the short chain amines themselves; a reaction mechanism is presented which involves attack of the aldehyde on the 6- hydroxydopa-derived free radical catalytic intermediate. With I,2-diam inoethane, 2-Br-ethylamine, and 2-Cl-ethylamine, the complex produced will form a stable 6-membered ring, causing irreversible inhibition of the enzyme.