EVIDENCE FOR A SINGLE CATALYTIC BINDING SITE ON HUMAN BRAIN TYPE B MONOAMINE OXIDASE

Abstract

The tricyclic antidepressant drug, amitriptyline, inhibited the B form of human brain mitochondrial monoamine oxidase (MAO) under normal atmospheric conditions in a noncompetitive manner when phenylethylamine (PEA) was used as substrate and competitively when benzylamine (BzNH2) was employed as substrate. PEA and BzNH2 inhibited each other''s degradation noncompetitively. Similar results were previously reported with human platelet MAO. The catalytic binding sites for PEA and BzNH2 on the B form of human brain MAO may be different. Attempts were made to further distinguish these catalytic binding sites on the brain oxidase using the irreversible MAO inhibitors, pargyline and clorgyline. Though these drugs have considerably different affinities for the B form of the oxidase, the degree to which either compound inhibited PEA or BzNH2 deamination was essentially identical. When incubations were performed at elevated O2 concentrations PEA and BzNH2 became mutually competitive inhibitors of each other''s metabolism and O2 amitriptyline inhibition of PEA deamination approached a competitive fashion. PEA and BzNH2 may share a common catalytic binding site on the B form of MAO and bind to an inhibitory site on the reduced form of the oxidase. Amitriptyline apparently also binds to both the oxidized and reduced forms of this human brain oxidase.