Interactions of Monoamine Oxidase from Human And Rat Liver Mitochondria with (S)-2-[4-(3-Flouro-Benzyloxy)-Benzylamino]-Propionamide | ||||
| Biochemistry Letters | ||||
| Article 20, Volume 12, Issue 1, 2016, Page 259-274 PDF (734.95 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/blj.2016.48197 | ||||
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| Authors | ||||
| Zakia Ben Ramadan1; Keith Tipton2; Safaa khater3 | ||||
| 1Department of Biochemistry, Faculty of Medicine University of Tripoli-Libya. | ||||
| 2Department of Biochemistry, Trinity College, Dublin 2, Ireland | ||||
| 3Department of Biochemistry, Zagazig University –Egypt. | ||||
| Abstract | ||||
| Background:The interactions of the anticonvulsant (S)-2-[4- (3-Flouro-Benzyloxy) Benzylamino]- Propionamide (FCE 26743) with MAO-A and MAO -B from human and rat liver mitochondria has been studied. Objective: This compound is an alanine derivative that differs from the parent anticonvulsant compound, 2-n-pentylamino acetamide in that alaninamide residue replaces the glycinamide moiety, and in the presence of a phenyl ring substituted in the para-position by a 3-flouro-benzyloxy group. Results: The results indicated that, The Ki values for rat and human MAO-A were > 1000 times higher than their corresponding values for rat and human MAO-Consistent with the IC50values that showed this compound to be > 1000 times more potent as an inhibitor of MAO-B than of MAO-A of the same species. There was an increase in the strength of inhibition when MAO-B was incubated with this compound. This was confirmed by the extended time-courses studies which showed a rather rapid increase in the degree of inhibition of MAO-B, despite incubation being continued for a total of 4h. This is consistent with FCE 26743 being a reversible inhibitor for MAO-A and a slow- binding reversible inhibitor of MAO-B.FCE 26743 was found to be a time-independent weak inhibitor of MAO-A from both rat and human preparations. However, there was a significant difference in the inhibitory potency of FCE 26743 with MAO-B from the two species, the Ki value for rat MAO-B was about two times higher than that for human MAOB. Conclusion: The FCE 26743 was not metabolized (in vitro) by either human or rat liver mitochondrial MAO-A or -B. Without enzyme-inhibitor preincubation FCE 26743 was found to be a competitive inhibitor of both MAO-A and MAO-B from rat and human liver mitochondria. | ||||
| Keywords | ||||
| Monoamine oxidase-A and-B (MAO-A& MAO -B); kinetics of inhibition; (S)-2-[4-(3-flourobenzyloxy)- benzylamino] propionamide; (FCE 26743); Inhibition Studies | ||||
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