Inactivation of monoamine oxidase A by the monoamine oxidase B inactivators 1-phenylcyclopropylamine, 1-benzylcyclopropylamine, and N-cyclopropyl-alpha-methylbenzylamine.
Three known mechanism-based inactivators of beef liver mitochondrial monoamine oxidase (MAO) B are tested as inactivators of human placental mitochondrial MAO A. 1-Phenylcyclopropylamine (1-PCPA), 1-benzylcyclopropylamine (1-BCPA), and N-cyclopropyl-alpha-methylbenzylamine (N-C alpha MBA) are time-dependent irreversible inactivators of MAO A. The KI values for 1-PCPA and N-C alpha MBA, analogues of the MAO B substrate benzylamine, are much higher with MAO A than with MAO B. Evidence is presented to show that 1-PCPA inactivates MAO A by attachment to the flavin cofactor, unlike the reaction with MAO B in which 1-PCPA can attach to both a cysteine residue and the flavin [Silverman, R.B., & Zieske, P.A. (1985) Biochemistry 24, 2128-2138]. The reaction of 1-BCPA with MAO A was too slow to study in detail. N-C alpha MBA exhibits the same properties toward inactivation of MAO A that it does for inactivation of MAO B. Attachment in both cases is shown to be to one cysteine residue per enzyme molecule. The results with 1-PCPA indicate that the active site topographies of MAO A and MAO B are different. The ability of N-C alpha MBA to undergo attachment to a cysteine residue in both MAO A and MAO B may lead the way toward peptide mapping of the two isozymes in order to determine differences in their primary structures.
Silverman
R B
RB
Department of Chemistry, Northwestern University, Evanston, Illinois 60208.
Hiebert
C K
CK
D001596:Benzylamines / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D003545:Cysteine; D005260:Female; D005415:Flavins; D006801:Humans; D066298:In Vitro Techniques; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013053:Spectrophotometry
D001596:Benzylamines; D003521:Cyclopropanes; D005415:Flavins; D008996:Monoamine Oxidase Inhibitors; C047294:1-benzylcyclopropylamine; C032446:N-(1-methyl)cyclopropylbenzylamine; C045293:1-phenylcyclopropylamine; D008995:Monoamine Oxidase; D003545:Cysteine