| 4084537 |
Yamasaki RB, Silverman RB: Mechanism for reactivation of N-cyclopropylbenzylamine-inactivated monoamine oxidase by amines. Biochemistry. 1985 Nov 5;24(23):6543-50.
The effect of 18 different amines, two mercaptans, and two alcohols on the reactivation of N-cyclopropylbenzylamine- (N-CBA-) inactivated bovine liver monoamine oxidase (MAO) is described. All of the compounds that reactivate the enzyme produce a time-dependent pseudo-first-order return of enzyme activity and exhibit saturation kinetics. There is no direct correlation between the ability of a compound to serve as a substrate for native MAO and its ability to reactivate N-CBA-inactivated MAO. Amines containing an aromatic moiety, in general, are better reactivators than the aliphatic amines. The amine must be primary or secondary in order for reactivation to occur. The distance between the aromatic portion and the amino group is critical to the reactivation properties of the compound. The mercaptans and alcohols do not reactivate N-CBA-inactivated MAO, nor do they interfere with the reactivation reaction by benzylamine. Three mechanisms for the reactivation reaction are considered. One involves initial Schiff base formation with the active site adduct produced by N-CBA inactivation of MAO followed by base-catalyzed beta-elimination to the imine of acrolein. The second mechanism is the same as the first except no prior Schiff base formation is invoked. The third mechanism is an SN2 displacement by the amine of the active site amino acid residue attached to the adduct. Experiments are carried out to exclude the SN2 mechanism. The results of the reactivation experiments favor the Shiff base mechanism. |
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