Kinetic Studies on the Interactions of Mitochondrial Monoamine Oxidase-B of Human and Pure Ox Liver with 2-(Benzylamino) Acetamide

Zakia M. Ben Ramadan, Keith F. Tipton, Maha M. El Deib
2016 Biochemistry Letters  
MAO-B), 2-(benzylamino) acetamide [FCE 25692], suicide substrate, Kinetic Parameters, Semicarbazide-Sensitive Amine Oxidases (SSAO) In an attempts to understand more precisely the role of monoamine oxidase (MAO-B) enzyme in the metabolism of the parent anticonvulsant 2-npentylaminoacetamide, the benzylamine derivative 2-benzylamino acetamide, also designated as FCE 25692, which used as a substrate and an inhibitor of MAO-B from human liver mitochondria and pure ox liver. The results obtained
more » ... icated that FCE 25692 to act as a suicide substrate with apparent K m values of 989 and 950 µM and V max values of 0.422 and 93.05 nMol.min -1 .mg -1 for human and the purified ox liver MAO-B, respectively, in a way that can explain that it is a better substrate rather than an inhibitor for MAO-B from both species, with partitions ratios of 1062 and 2733 mol of product per mol of enzyme inactivated, for human and ox preparation, respectively. Moreover, the turnover numbers (k cat ) and the k cat /K m values confirmed the fact that FCE 25692 is somewhat a better substrate for MAO-B purified from ox liver than from human liver, with k cat /K m values of 40.3 and 17.1 min -1 .mM -1 , respectively. The progress curves for the inhibition of MAO-B showed that FCE 25692 has an equipotent time-dependent inhibitor of MAO-B in both preparations. It can be confirmed from the close similar inactivation constant k in and half-life values for MAO-B from both preparations; the t 1/2 for the purified ox MAO-B (49.9 min) and for human . Despite the fact that benzylamine is a substrate for the semicarbazide-sensitive amine oxidase (SSAO; EC, FCE 25692 was found not to be a substrate or an inhibitor for any of that enzyme from ox plasma or lung.
doi:10.21608/blj.2016.48189 fatcat:rixbqkzz2zd4vcwe74b7tveetu