1-Phenylcyclobutylamine, the First in a New Class of Monoamine Oxidase Inactivators. Further Evidence for a Radical Intermediate

Richard B. Silverman*, Paul A. Zieske

*Corresponding author for this work

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

1-Phenylcyclobutylamine (PCBA) is shown to be both a substrate and a time-dependent irreversible inactivator of monoamine oxidase (MAO). Inactivation results in attachment to the flavin cofactor. For every molecule of PCBA leading to inactivation, 325 molecules are converted to product. The first metabolite formed is identified as 2-phenyl-1-pyrroline; then after a lag time, 3-benzoylpropanal and 3-benzoylpropionic acid are generated. The 3-benzoylpropanal is a product of MAO-catalyzed oxidation of 2-phenyl-1-pyrroline (presumably, of its hydrolysis product, γ-aminobutyrophenone). The aldehyde is nonenzymatically oxidized by nascent hydrogen peroxide to the carboxylic acid. These results are consistent with a one-electron oxidation of PCBA to the amine radical cation followed by homolytic cyclobutane ring cleavage. The resulting radical can partition between cyclization (an intramolecular radical trap) to the 2-phenylpyrrolinyl radical and attachment to the flavin. The cyclic radical can be further oxidized by one electron to 2-phenyl-1-pyrroline. PCBA represents the first in the cyclobutylamine class of MAO inactivators and strongly supports involvement of a radical mechanism for MAO-catalyzed amine oxidations.

Original languageEnglish (US)
Pages (from-to)341-346
Number of pages6
JournalBiochemistry
Volume25
Issue number2
DOIs
StatePublished - Jan 1986

ASJC Scopus subject areas

  • Biochemistry

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