Oxidation and Enzyme-activated Irreversible Inhibition of Rat and Ox Liver Mitochondrial Monoamine Oxidase-B by 2-(Benzylamino) Acetamide

The interactions of the anticonvulsant 2-n-pentylaminoacetamideanalogue, 2-benzylamino acetamide (FCE 25692) with MAO-B from rat and Ox liver mitochondria have been studied. This compound involves retention of the aminoacetamide portion of the parent compound but replacement of the pentyl moiety with benzylamine which is a good substrate for MAO-B. The results indicated FCE 25692 to be a good substrate for MAO-B from both preparations used with apparent Km values of 229.8 and 920.0 μM and Vmax values of 0.230 and 0.989nMol.min^-1.mg^-1 for rat and ox liver mitochondrial MAO-B, respectively. It also acts as a suicide substrate and is a better substrate than it is an inhibitor for MAO-B from both species, with partitions ratios of 816.7 and 2120 mol of product per mol of enzyme inactivated, respectively for rat and ox liver mitochondrial MAOB. The partition ratio for ox liver MAO-B was considerably higher than that of the enzyme from rat liver and the half-life (t_1/2) of ox liver MAOB was a little larger than its respective (t_1/2) value for the enzyme from rat liver. The turnover numbers (k_cat) and the k_cat/K_m values are compared with the inhibition specificity constants (K_in /K ) these values confirmed the fact that FCE 25692 is a better substrate for rat liver MAO-B than for ox liver MAO-B with k_cat/K_m values of (118 and 46.1 min^-1.mM^-1, respectively). While the inactivation constant kin values showed that FCE 25692 is somewhat a better inhibitor for ox liver MAO-B than rat liver MAO-B (0.020 and 0.033, respectively). However the progress curves for the inhibition of MAO-B from both preparations showed that FCE 25692 was a better inhibitor of MAOB from rat preparation than ox preparation.